Cross-talk between HIF and PD-1/PD-L1 pathways in carcinogenesis and therapy
Open accessAbstract
Tumor-associated hypoxia plays an important role in carcinogenesis and metastasis. The expression, activation, and stabilization of hypoxia-inducible transcription factors (HIFs) support malignant cell survival, proliferation, plasticity, and motility. Hypoxia also upregulates the expression of programmed cell death ligand 1 (PD-L1) in malignant and immune regulatory cells. Therefore, the combination of HIF inhibitors and checkpoint inhibitors (CPIs) is promising for boosting antitumor immunity and diminishing malignant cell plasticity and therapy resistance. In this issue of the JCI, Salman et al. report the development of a specific agent that inhibited HIF-1/2-mediated gene expression in tumor cells and suppressed tumor growth. Bailey, Liu, et al. in this issue demonstrate that targeting HIF-1α abrogated PD-L1-mediated immune evasion by suppressing PD-L1 expression on malignant and myeloid regulatory cells, causing tumor rejection. These findings suggest that targeting the HIF/PD-L1 axis with specific HIF inhibitors should improve the safety and efficacy of CPIs for cancer therapy.
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Written from the paper’s full text.
TL;DR
This JCI commentary reviews the cross-talk between hypoxia-inducible factors (HIFs) and the PD-1/PD-L1 axis in cancer, arguing that combining HIF inhibitors with checkpoint inhibitors (CPIs) could improve antitumor immunity and reduce therapy resistance. It highlights two companion JCI studies showing that HIF inhibition suppresses tumor growth and PD-L1–mediated immune evasion.
Key findings
- Hypoxia stabilizes HIF-1/HIF-2, which promote angiogenesis, immunosuppression, EMT, and metabolic reprogramming, and upregulate PD-L1 on malignant and myeloid regulatory cells; hypoxia correlates with worse prognosis and resistance to therapy.
- Salman et al. developed a low-molecular-weight agent inhibiting HIF-1/2–mediated gene expression that suppressed tumor growth in mice, reduced vascularization and immunosuppression (fewer TAMs and MDSCs via suppressed IL-4, IL-13, CXCL1), increased CTL/NK infiltration (via CXCL9/CXCL10), and raised the complete response rate to anti–PD-1 from 25% to 67%.
- Bailey, Liu, et al. showed that pharmaceutical or genetic HIF-1α targeting suppressed PD-L1 on malignant cells and myeloid regulatory cells, reactivated TILs, caused tumor rejection, downregulated PD-1, upregulated granzyme B and perforin, and potentiated anti–CTLA-4 therapy.
- Bailey, Liu, et al. also found that HIF-1α inhibition blocked PD-L1 at the tumor site but induced PD-L1 in normal tissues, suggesting a route to safer immunotherapy by differential PD-L1 regulation.
Methods
- Design: a commentary/review article in the Journal of Clinical Investigation discussing the HIF/PD-L1 axis and two companion studies published in the same issue.
- Data: no primary data; the article synthesizes published experimental and clinical literature (including refs. 1–25) and describes the findings of Salman et al. (ref. 23) and Bailey, Liu, et al. (ref. 24).
- Analysis: narrative synthesis of mechanisms and therapeutic implications, with a proposed framework for combining HIF inhibitors with CPIs.
Limitations
- Not stated in the paper (the commentary does not include a limitations section).
- Evident from the text: this is a commentary without original data, so its conclusions rest on the two cited companion studies and prior literature; the highlighted findings derive largely from murine tumor models, and the authors note that testing in different tumor models and understanding interactions with TGF-β, IL-1, hormones, and growth factors remain necessary.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
0 of 29 cited sources checked · 0 supported · 0 flagged
- Interpretationcitation
Targeting the HIF/PD-L1 axis with specific HIF inhibitors should improve the safety and efficacy of CPIs for cancer therapy.
“These findings suggest that targeting the HIF/PD-L1 axis with specific HIF inhibitors should improve the safety and efficacy of CPIs for cancer therapy.”
Quote in the paperNot a substantial claim- Rests on an assumption: The murine tumor model results for HIF inhibitors and CPI combinations are predictive of human cancer therapy.
- Premisecitation
The expression, activation, and stabilization of HIFs support malignant cell survival, proliferation, plasticity, and motility.
“The expression, activation, and stabilization of hypoxia-inducible transcription factors (HIFs) support malignant cell survival, proliferation, plasticity, and motility.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [1] source
Not checked in the free run.
- Premisecitation
Tumor-associated hypoxia plays an important role in carcinogenesis and metastasis.
“Tumor-associated hypoxia plays an important role in carcinogenesis and metastasis.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [1] source
Not checked in the free run.
- Premisecitation
Hypoxia upregulates the expression of PD-L1 in malignant and immune regulatory cells.
“Hypoxia also upregulates the expression of programmed cell death ligand 1 (PD-L1) in malignant and immune regulatory cells.”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
HIF-1 promotes tumor progression via the stimulation of angiogenesis, immunosuppression, EMT, and metabolic reprogramming.
“HIF-1 promotes tumor progression via the stimulation of angiogenesis, immunosuppression, epithelial-mesenchymal transition (EMT), and metabolic reprogramming, supporting malignant cell survival, proliferation, plasticity, and motility (ref. 1 and Figure 1).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites ref. 1
Not checked in the free run.
- Premisecitation
Recent data indicate that hypoxia is also able to upregulate expression of PD-L1 in malignant cells via HIF-1α and HIF-2α.
“Recent data indicate that hypoxia is also able to upregulate expression of PD-L1 in malignant cells via HIF-1α and HIF-2α (17).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [17] source
Not checked in the free run.
- Premisecitation
Analysis of the melanoma genome atlas data shows a correlation of the HIF-1 signaling signature with PD-L1 mRNA expression, especially with IFN-γ-induced expression of PD-L1 mRNA.
“For instance, analysis of the melanoma genome atlas data shows a correlation of the HIF-1 signaling signature with PD-L1 mRNA expression, especially with IFN-γ–induced expression of PD-L1 mRNA (25).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [25] source
Not checked in the free run.
- Premisecitation
HIF-1α inhibition synergizes with anti-PD-1 therapy to inhibit tumor development.
“Importantly, HIF-1α inhibition synergizes with anti–PD-1 therapy to inhibit tumor development (Figure 1).”
Quote in the paperSubstantial claim - Premisecitation
HIF-1α inhibition potentiated immunotherapeutic effects of anti-CTLA-4 therapy in experimental models.
“Importantly, HIF-1α inhibition potentiated immunotherapeutic effects of anti–CTLA-4 therapy in experimental models.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [24] Bailey, 2022, Targeting HIF-1α abrogates PD-L1–mediated immune evasion in tumor microenvironment but promotes tolerance in normal tissues, J Clin Invest source
Not checked in the free run.
- Premisecitation
Administration of the HIF inhibitor in tumor-bearing mice resulted in inhibition of tumor growth.
“Administration of the HIF inhibitor in tumor-bearing mice resulted in inhibition of tumor growth.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [23] Salman, 2022, HIF inhibitor 32-134D eradicates murine hepatocellular carcinoma in combination with anti-PD1 therapy, J Clin Invest source
Not checked in the free run.
- Interpretationcitation
HIF-1α inhibition represents a promising companion for different CPIs.
“Thus, it is conceivable that HIF-1α inhibition represents a promising companion for different CPIs.”
Quote in the paperNot a substantial claim- Rests on an assumption: The murine tumor model results for HIF inhibitors and CPI combinations are predictive of human cancer therapy.
- Premisecitation
Hypoxia upregulates expression of immune checkpoint molecules, such as VISTA and PD-L1, on MDSCs, promoting their immunosuppressive phenotype.
“In addition, hypoxia upregulates expression of immune checkpoint molecules, such as VISTA and programmed cell death ligand 1 (PD-L1), on myeloid-derived suppressor cells (MDSCs), promoting their immunosuppressive phenotype (17, 18).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Hypoxia impacts the efficiency of cancer immunotherapy by contributing to the immune-eliminated phenotype.
“For instance, hypoxia impacts the efficiency of cancer immunotherapy by contributing to the immune-eliminated phenotype, which is a key barrier to the therapeutic effect of adoptive cell therapy (5).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [5] source
Not checked in the free run.
- Premisecitation
The HIF inhibitor boosted the percentage of mice with a complete response to anti-PD-1 CPI from 25% to 67%.
“Importantly, the HIF inhibitor boosted the percentage of mice with a complete response to anti–PD-1 CPI from 25% to 67% (23).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [23] Salman, 2022, HIF inhibitor 32-134D eradicates murine hepatocellular carcinoma in combination with anti-PD1 therapy, J Clin Invest source
Not checked in the free run.
- Interpretationcitation
Promotion of immune tolerance by differential regulation of PD-L1 in normal and cancer tissues is an important approach for safer and more successful immunotherapy.
“Promotion of immune tolerance by differential regulation of PD-L1 in normal and cancer tissues is an important approach for safer and more successful immunotherapy (24).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [24] Bailey, 2022, Targeting HIF-1α abrogates PD-L1–mediated immune evasion in tumor microenvironment but promotes tolerance in normal tissues, J Clin Invest source
Not checked in the free run.
- Rests on an assumption: HIF-1α inhibition-induced PD-L1 expression in normal tissues leads to immune tolerance in humans.
- May combine two claims. 15
- Classified as probably not a substantial claim. 3
May combine two claims.
InterpretationreasoningThe combination of HIF inhibitors and checkpoint inhibitors (CPIs) is promising for boosting antitumor immunity and diminishing malignant cell plasticity and therapy resistance.
“Therefore, the combination of HIF inhibitors and checkpoint inhibitors (CPIs) is promising for boosting antitumor immunity and diminishing malignant cell plasticity and therapy resistance.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationBailey, Liu, et al. demonstrated that targeting HIF-1α abrogated PD-L1-mediated immune evasion by suppressing PD-L1 expression on malignant and myeloid regulatory cells, causing tumor rejection.
“Bailey, Liu, et al. in this issue demonstrate that targeting HIF-1α abrogated PD-L1–mediated immune evasion by suppressing PD-L1 expression on malignant and myeloid regulatory cells, causing tumor rejection.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [24] Bailey, 2022, Targeting HIF-1α abrogates PD-L1–mediated immune evasion in tumor microenvironment but promotes tolerance in normal tissues, J Clin Invest source
Not checked in the free run.
May combine two claims.
PremisecitationHypoxia correlates with worse prognosis in different cancer types and imparts resistance to different therapeutic approaches.
“Hence, in a clinical setting, hypoxia correlates with worse prognosis in different cancer types and, in addition, imparts resistance to different therapeutic approaches (4).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [4] Semenza, 2002, HIF-1 and tumor progression: pathophysiology and therapeutics, Trends Mol Med source
Not checked in the free run.
May combine two claims.
PremisecitationSalman et al. developed a specific agent that inhibited HIF-1/2-mediated gene expression in tumor cells and suppressed tumor growth.
“In this issue of the JCI, Salman et al. report the development of a specific agent that inhibited HIF-1/2–mediated gene expression in tumor cells and suppressed tumor growth.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [23] Salman, 2022, HIF inhibitor 32-134D eradicates murine hepatocellular carcinoma in combination with anti-PD1 therapy, J Clin Invest source
Not checked in the free run.
May combine two claims.
PremisecitationClinical studies of HIF inhibitors indicate benefit and justify further evaluation either as a single agent or in combination with other antitumor agents.
“Clinical studies of HIF inhibitors indicate benefit and justify further evaluation either as a single agent or in combination with other antitumor agents (6).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [6] source
Not checked in the free run.
May combine two claims.
PremisecitationIn a murine melanoma model, inhibition of HIF-1α transcriptional activity results in CCL2- and CCL5-mediated increases in NK cells and CTLs in the tumor bed, and improves the antitumor potential of peptide vaccination and anti-PD-1 blocking antibody.
“In a murine melanoma model, inhibition of HIF-1α transcriptional activity results in CCL2- and CCL5-mediated increases in NK cells and CTLs in the tumor bed, and improves the antitumor potential of peptide vaccination and anti–PD-1 blocking antibody (22).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [22] source
Not checked in the free run.
May combine two claims.
PremisecitationCombination therapies based on PD-1/PD-L1 blockade for a wide range of cancer types have been introduced and can improve patient survival.
“Combination therapies based on PD-1/PD-L1 blockade for a wide range of cancer types have been introduced and can improve patient survival (20).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [20] source
Not checked in the free run.
May combine two claims.
PremisecitationInducible expression of PD-L1 at the tumor site is involved in cancer escape because its binding to PD-1 on effector T cells causes T cell exhaustion and apoptosis, while apoptosis of regulatory T cells is inhibited.
“Inducible expression of PD-L1 at the tumor site is involved in cancer escape because its binding to PD-1 on effector T cells causes T cell exhaustion and apoptosis, while apoptosis of regulatory T cells is inhibited (19).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [19] Han, 2020, PD-1/PD-L1 pathway: current researches in cancer, Am J Cancer Res
Not checked in the free run.
May combine two claims.
PremisecitationHIF-1α inhibition in vivo downregulated PD-1 expression, upregulated cytolytic effector molecules granzyme B and perforin, and decreased apoptosis in TILs in the tumor microenvironment.
“HIF-1α inhibition in vivo downregulated PD-1 expression, upregulated cytolytic effector molecules granzyme B and perforin, and decreased apoptosis in TILs in the tumor microenvironment.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [24] Bailey, 2022, Targeting HIF-1α abrogates PD-L1–mediated immune evasion in tumor microenvironment but promotes tolerance in normal tissues, J Clin Invest source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationBailey, Liu, et al. confirmed these results.
“Bailey, Liu, et al. confirmed these results (24).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [24] Bailey, 2022, Targeting HIF-1α abrogates PD-L1–mediated immune evasion in tumor microenvironment but promotes tolerance in normal tissues, J Clin Invest source
Not checked in the free run.
Classified as probably not a substantial claim.
InterpretationcitationSalman et al. support the notion that highly specific and nontoxic HIF inhibitors deserve further investigation when applied alone or in combination with CPIs and other targeted therapy.
“Salman et al. also support the notion that highly specific and nontoxic HIF inhibitors deserve further investigation when applied alone or in combination with CPIs and other targeted therapy (23).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [23] Salman, 2022, HIF inhibitor 32-134D eradicates murine hepatocellular carcinoma in combination with anti-PD1 therapy, J Clin Invest source
Not checked in the free run.
- Rests on an assumption: HIF inhibitors can be developed that are highly specific and nontoxic in humans.
May combine two claims.
PremisecitationThe synthesized low-molecular-weight agent targeted both HIF-1 and HIF-2, inducing HIF-α subunit degradation and thus inhibiting activation of HIF-1- and HIF-2-target gene transcription.
“The synthesized low-molecular-weight agent targeted both HIF-1 and HIF-2, inducing HIF-α subunit degradation and thus inhibiting activation of HIF-1– and HIF-2–target gene transcription.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [23] Salman, 2022, HIF inhibitor 32-134D eradicates murine hepatocellular carcinoma in combination with anti-PD1 therapy, J Clin Invest source
Not checked in the free run.
May combine two claims.
Premisenone givenHypoxia induces radioresistance and resistance to a variety of chemotherapeutic agents, affects antitumoral immune responses, and controls crucial regulatory pathways.
“Numerous experimental and clinical data reveal that hypoxia induces radioresistance and resistance to a variety of chemotherapeutic agents, affects antitumoral immune responses, and controls crucial regulatory pathways, impacting key aspects of cancer biology.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationIn vivo treatment with PX-478 and anti-PD-1 antibodies suppresses tumor growth and prolongs animal survival, which is associated with downregulation of EMT phenotypes, lower immunosuppression, and enhanced TIL homing.
“For instance, in vivo treatment with PX-478 and anti–PD-1 antibodies suppresses tumor growth and prolongs animal survival, which is associated with downregulation of EMT phenotypes, lower immunosuppression, and enhanced TIL homing (21).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [21] source
Not checked in the free run.
May combine two claims.
PremisecitationAlthough HIF-1α inhibition blocked PD-L1 expression at the tumor site, it induced PD-L1 in normal tissues.
“The authors also reported an interesting observation; although HIF-1α inhibition blocked PD-L1 expression at the tumor site, it induced PD-L1 in normal tissues.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [24] Bailey, 2022, Targeting HIF-1α abrogates PD-L1–mediated immune evasion in tumor microenvironment but promotes tolerance in normal tissues, J Clin Invest source
Not checked in the free run.
May combine two claims.
PremisecitationIn vivo alterations of the tumor immune environment involved fewer protumorigenic TAMs and MDSCs due to the suppression of IL-4, IL-13, and CXCL1 expression, and elevated infiltration by antitumor CTLs and NK cells attracted by elevated CXCL9 and CXCL10 levels.
“In vivo alterations of the tumor immune environment involved fewer protumorigenic tumor-associated macrophages (TAMs) and MDSCs due to the suppression of IL-4, IL-13, and CXCL1 expression, and elevated infiltration by antitumor CTLs and NK cells attracted by elevated CXCL9 and CXCL10 levels.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [23] Salman, 2022, HIF inhibitor 32-134D eradicates murine hepatocellular carcinoma in combination with anti-PD1 therapy, J Clin Invest source
Not checked in the free run.
May combine two claims.
PremisecitationThe smaller tumors were associated with lower tumor vascularization due to decreased expression of multiple genes encoding angiogenic factors, and lower immunosuppression due to diminished expression of genes encoding proteins mediating immunosuppression.
“The smaller tumors were associated with lower tumor vascularization due to decreased expression of multiple genes encoding angiogenic factors, and lower immunosuppression due to diminished expression of genes encoding proteins mediating immunosuppression.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [23] Salman, 2022, HIF inhibitor 32-134D eradicates murine hepatocellular carcinoma in combination with anti-PD1 therapy, J Clin Invest source
Not checked in the free run.
Probably not a substantial claim: may not pass S2 (checkable).
InterpretationreasoningFindings on differential regulation of PD-L1 expression by HIF suggest that a combination of HIF inhibition with some CPIs, like anti-CTLA-4, should be experimentally verified.
“The findings on differential regulation of PD-L1 expression by HIF suggest that a combination of HIF inhibition with some CPIs, like anti–CTLA-4, for example, should be experimentally verified.”
Quote in the paperNot a substantial claim
The paper relies on this without support.
The murine tumor model results for HIF inhibitors and CPI combinations are predictive of human cancer therapy.
“These findings suggest that targeting the HIF/PD-L1 axis with specific HIF inhibitors should improve the safety and efficacy of CPIs for cancer therapy.”
The paper relies on this without support.
HIF inhibitors can be developed that are highly specific and nontoxic in humans.
“Salman et al. also support the notion that highly specific and nontoxic HIF inhibitors deserve further investigation when applied alone or in combination with CPIs and other targeted therapy (23).”
The paper relies on this without support.
HIF-1α inhibition-induced PD-L1 expression in normal tissues leads to immune tolerance in humans.
“Promotion of immune tolerance by differential regulation of PD-L1 in normal and cancer tissues is an important approach for safer and more successful immunotherapy (24).”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Hypoxia can directly upregulate expression of various cellular immune checkpoints, such as PD-L1, in the tumor microenvironment.
“Hypoxia can directly upregulate the expression of various cellular immune checkpoints (such as programmed cell death‐ligand 1, PD‐L1) in the TME.”
From Hypoxia signaling in cancer: Implications for therapeutic interventions (2023) · cites this paper as [108]
Cites
1 retracted
Lee, K., Qian, D. Z., Rey, S., Wei, H., Liu, J. O., & Semenza, G. L. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812801106 · Cited by 289 · see citing works
RetractedNoman, M. Z., Desantis, G., Janji, B., Hasmim, M., Karray, S., Dessen, P., Bronte, V., & Chouaib, S. (2014) · Journal of Experimental Medicine · doi:10.1084/jem.20131916 · Cited by 2,166 · see citing works
PD-1/PD-L1 pathway: current researches in cancer.
Han, Y., Liu, D., & Li, L. (2020) · PubMed Central · Cited by 1,602 · see citing works
Combination strategies with PD-1/PD-L1 blockade: current advances and future directions
Yi, M., Zheng, X., Niu, M., Zhu, S., Ge, H., & Wu, K. (2022) · Molecular Cancer · doi:10.1186/s12943-021-01489-2 · Cited by 1,445 · see citing works
HIF-1 and tumor progression: pathophysiology and therapeutics
Semenza, G. L. (2002) · Trends in Molecular Medicine · doi:10.1016/s1471-4914(02)02317-1 · Cited by 1,060 · see citing works
Hypoxia, Clonal Selection, and the Role of HIF-1 in Tumor Progression
Semenza, G. L. (2000) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409230091169186 · Cited by 651 · see citing works
Berchem, G., Noman, M. Z., Bosseler, M., Paggetti, J., Baconnais, S., Cam, É. L., Nanbakhsh, A., Moussay, E., Mami‐Chouaib, F., Janji, B., et al. (2015) · OncoImmunology · doi:10.1080/2162402x.2015.1062968 · Cited by 321 · see citing works
Koh, M. Y., Spivak-Kroizman, T., Venturini, S., Welsh, S., Williams, R. R., Kirkpatrick, D. L., & Powis, G. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-07-0463 · Cited by 309 · see citing works
HIF Inhibitors: Status of Current Clinical Development
Fallah, J., & Rini, B. I. (2019) · Current Oncology Reports · doi:10.1007/s11912-019-0752-z · Cited by 308 · see citing works
Deng, J., Li, J., Sarde, A., Lines, J. L., Lee, Y.-C., Qian, D. C., Pechenick, D. A., Manivanh, R., Le Mercier, I., Lowrey, C. H., et al. (2019) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-18-0507 · Cited by 224 · see citing works
Bailey, C. M., Liu, Y., Liu, M., Du, X., Devenport, M., Zheng, P., Liu, Y., & Wang, Y. (2022) · Journal of Clinical Investigation · doi:10.1172/jci150846 · Cited by 151 · see citing works
Lequeux, A., Noman, M. Z., Xiao, M., Van Moer, K., Hasmim, M., Benoit, A., Bosseler, M., Viry, E., Arakelian, T., Berchem, G., et al. (2021) · Oncogene · doi:10.1038/s41388-021-01846-x · Cited by 129 · see citing works
Salman, S., Meyers, D. J., Wicks, E. E., Lee, S. N., Datan, E., Thomas, A. M., Anders, N. M., Hwang, Y., Lyu, Y., Yang, Y., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci156774 · Cited by 111 · see citing works
Hypoxia Signaling in Cancer: From Basics to Clinical Practice
Sebestyén, A., Kopper, L., Dankó, T., & Tímár, J. (2021) · Pathology and Oncology Research · doi:10.3389/pore.2021.1609802 · Cited by 110 · see citing works
Progress toward Overcoming Hypoxia-Induced Resistance to Solid Tumor Therapy
Reginato, M., & Karakashev, S. (2015) · Cancer Management and Research · doi:10.2147/cmar.s58285 · Cited by 95 · see citing works
Luo, F., Lu, F.-T., Cao, J.-X., Ma, W.-J., Xia, Z.-F., Zhan, J.-H., Zeng, K.-M., Huang, Y., Zhao, H.-Y., & Zhang, L. (2022) · Cancer Letters · doi:10.1016/j.canlet.2022.01.027 · Cited by 95 · see citing works
Autophagic degradation of GZMB/granzyme B
Viry, E., Bagińska, J., Berchem, G., Noman, M. Z., Medves, S., Chouaı̈b, S., & Janji, B. (2013) · Autophagy · doi:10.4161/auto.26924 · Cited by 92 · see citing works
Lee, S., Jee, J., Bae, J., Liu, K., & Lee, Y. M. (2015) · Journal of Cellular Physiology · doi:10.1002/jcp.24813 · Cited by 86 · see citing works
HIF-1α Metabolic Pathways in Human Cancer
Elzakra, N., & Kim, Y. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-51652-9_17 · Cited by 67 · see citing works
Inhibition of Hypoxia-Inducible Factor-1α (HIF-1α) Protein Synthesis by DNA Damage Inducing Agents
Lou, J. J. W., Chua, Y. L., Chew, E., Gao, J., Bushell, M., & Hagen, T. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010522 · Cited by 57 · see citing works
Small molecules targeting HIF-1α pathway for cancer therapy in recent years.
Tang, W., & Zhao, G. (2020) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2019.115235 · Cited by 50 · see citing works
Li, L., Lin, X., Shoemaker, A. R., Albert, D. H., Fesik, S. W., & Shen, Y. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-2842 · Cited by 48 · see citing works
Jasinghe, V. J., Xie, Z., Zhou, J., Khng, J., Poon, L.-F., Palaniyandi, S., Glaser, K. B., Albert, D. H., Davidsen, S. K., & Chen, C.-S. (2008) · Journal of Hepatology · doi:10.1016/j.jhep.2008.08.010 · Cited by 34 · see citing works
Multifaceted Interplay between Hormones, Growth Factors and Hypoxia in the Tumor Microenvironment
Lappano, R., Todd, L. A., Stanic, M., Cai, Q., Maggiolini, M., Marincola, F., & Pietrobon, V. (2022) · Cancers · doi:10.3390/cancers14030539 · Cited by 32 · see citing works
van Duijn, A., Willemsen, K. J., van Uden, N. O. P., Hoyng, L., Erades, S., Koster, J., Luiten, R. M., & Bakker, W. J. (2022) · Cancer Immunology, Immunotherapy · doi:10.1007/s00262-021-03007-1 · Cited by 24 · see citing works
Flagged first, then by citations
1 of the 26 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
PD-1/PD-L1 checkpoint inhibitors in advanced hepatocellular carcinoma immunotherapy
Li, Q., Han, J., Yang, Y., & Chen, Y. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1070961 · Cited by 252 · see citing works
Metabolic reprogramming and immune evasion: the interplay in the tumor microenvironment
Zhang, H., Li, S., Wang, D., Liu, S. M., Xiao, T., Gu, W., Yang, H., Wang, H. Z., Yang, M., & Chen, P. (2024) · Biomarker Research · doi:10.1186/s40364-024-00646-1 · Cited by 169 · see citing works
Regulatory T cells in immune checkpoint blockade antitumor therapy
Zhang, A., Fan, T., Liu, Y., Yu, G., Li, C., & Jiang, Z. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02156-y · Cited by 153 · see citing works
Bigos, K. J. A., Quiles, C. G., Lunj, S., Smith, D. J., Krause, M., Troost, E. G. C., West, C., Hoskin, P., & Choudhury, A. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1331355 · Cited by 142 · see citing works
Ren, Y., Wang, R., Weng, S., Xu, H., Zhang, Y., Chen, S., Liu, S., Ba, Y., Zhou, Z., Luo, P., et al. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01831-w · Cited by 138 · see citing works
Yang, J., Ren, B., Yin, X., Xiang, L., Hua, Y., Huang, X., Wang, H., Mao, Z., Chen, W., & Deng, J. (2024) · Advanced Materials · doi:10.1002/adma.202402720 · Cited by 125 · see citing works
PD-L1: From cancer immunotherapy to therapeutic implications in multiple disorders
Lee, D., Cho, M., Kim, E., Seo, Y., & Cha, J. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.09.026 · Cited by 124 · see citing works
Hypoxia signaling in cancer: Implications for therapeutic interventions
Zhuang, Y., Liu, K., He, Q., Gu, X., Jiang, C., & Wu, J. (2023) · MedComm · doi:10.1002/mco2.203 · Cited by 119 · see citing works
Alleviating hypoxia to improve cancer immunotherapy
Fan, P., Zhang, N., Candi, E., Agostini, M., Piacentini, M., Bernassola, F., Bove, P., Alessandro, M., Giuseppe, N., Valentina, R., et al. (2023) · Oncogene · doi:10.1038/s41388-023-02869-2 · Cited by 99 · see citing works
Fu, Y., Mackowiak, B., Feng, D., Lu, H., Guan, Y., Lehner, T., Pan, H., Wang, X. W., He, Y., & Gao, B. (2023) · Gut · doi:10.1136/gutjnl-2022-327924 · Cited by 86 · see citing works
Chen, X., Feng, L., Huang, Y., Wu, Y., & Xie, N. (2022) · Cancers · doi:10.3390/cancers15010104 · Cited by 81 · see citing works
Modulation of macrophage metabolism as an emerging immunotherapy strategy for cancer
Dussold, C., Zilinger, K., Turunen, J. R., Heimberger, A. B., & Miska, J. M. (2024) · Journal of Clinical Investigation · doi:10.1172/jci175445 · Cited by 78 · see citing works
Alizadeh, H., Akbarabadi, P., Dadfar, A., Tareh, M. R., & Soltani, B. M. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02345-3 · Cited by 67 · see citing works
HIF-1 and HIF-2 in cancer: structure, regulation, and therapeutic prospects
Shi, Y., & Gilkes, D. M. (2025) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-024-05537-0 · Cited by 70 · see citing works
Adjuvant Properties of Caffeic Acid in Cancer Treatment
Cortez, N., Villegas, C., Burgos, V., Cabrera‐Pardo, J. R., Ortíz, L., González‐Chavarría, I., Nchiozem‐Ngnitedem, V., & Paz, C. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25147631 · Cited by 60 · see citing works
Metabolic Reprogramming in Cancer: Implications for Immunosuppressive Microenvironment
Aden, D., Sureka, N., Zaheer, S., Chaurasia, J. K., & Zaheer, S. (2024) · Immunology · doi:10.1111/imm.13871 · Cited by 54 · see citing works
Immune checkpoint inhibitors in bone metastasis: Clinical challenges, toxicities, and mechanisms
Joseph, G. J., Johnson, D. B., & Johnson, R. W. (2023) · Journal of bone oncology · doi:10.1016/j.jbo.2023.100505 · Cited by 53 · see citing works
Xiang, Y., Chen, Q., Nan, Y., Liu, M., Xiao, Z., Yang, Y., Zhang, J., Ying, X., Long, X., Wang, S., et al. (2023) · Advanced Functional Materials · doi:10.1002/adfm.202312092 · Cited by 44 · see citing works
A Roadmap of CAR-T-Cell Therapy in Glioblastoma: Challenges and Future Perspectives
Montoya, M., Gallus, M., Phyu, S. M., Haegelin, J., de Groot, J., & Okada, H. (2024) · Cells · doi:10.3390/cells13090726 · Cited by 40 · see citing works
Yu, J. H., Qu, S., Shi, G., Fan, L., Qian, J., Sun, Z., Lu, F., & Han, X. (2024) · ACS Nano · doi:10.1021/acsnano.4c11334 · Cited by 35 · see citing works
Yu, S., Su, S., Wang, P., Li, J., Chen, C., Xin, H., Gong, Y., Wang, H., Ye, X., Mao, L., et al. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.216872 · Cited by 33 · see citing works
Zheng, H., Wang, G., Liu, M., & Cheng, H. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1168226 · Cited by 32 · see citing works
Zhang, T., Lv, Q., & Jin, W. (2024) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2024.189137 · Cited by 34 · see citing works
Cui, Z., Ruan, Z., Li, M., Ren, R., Ma, Y., Zeng, J., Sun, J., Ye, W., Xu, W., Guo, X., et al. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.110652 · Cited by 30 · see citing works
Liu, J., Zhang, X., Fan, X., Liu, P., Mi, Z., Tan, H., & Rong, P. (2025) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-025-03477-6 · Cited by 30 · see citing works
Navigating the Immune Maze: Pioneering Strategies for Unshackling Cancer Immunotherapy Resistance
Yao, L., Wang, Q., & Ma, W. (2023) · Cancers · doi:10.3390/cancers15245857 · Cited by 27 · see citing works
Light‐Enhanced Hypoxia‐Responsive Gene Editing for Hypoxia‐Resistant Photodynamic and Immunotherapy
Qu, S., Ji, Y., Fan, L., Yan, T., Zhu, G., Song, H., Yang, K., & Han, X. (2023) · Advanced Healthcare Materials · doi:10.1002/adhm.202302615 · Cited by 26 · see citing works
Crosstalk between hypoxia-induced pyroptosis and immune escape in cancer: From mechanisms to therapy
Meybodi, S. M., Ejlalidiz, M., Manshadi, M. R., Raeisi, M., Zarin, M., Kalhor, Z., Saberiyan, M., & Hamblin, M. R. (2024) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2024.104340 · Cited by 24 · see citing works
Novel Approaches with HIF-2α Targeted Therapies in Metastatic Renal Cell Carcinoma
Nguyen, C. B., Oh, E., Bahar, P., Vaishampayan, U. N., Else, T., & Alva, A. S. (2024) · Cancers · doi:10.3390/cancers16030601 · Cited by 25 · see citing works
Combination therapy with nivolumab (anti-PD-1 monoclonal antibody): A new era in tumor immunotherapy
Kiasari, B. A., Abbasi, A., Darestani, N. G., Adabi, N., Moradian, A., Yazdani, Y., Hosseini, G. S., Gholami, N., & Janati, S. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.109365 · Cited by 25 · see citing works
Yuan, X., Liu, X., Jiang, D., Zheng, Z., Ma, X., Wu, S., Li, X., Lü, J., & Fu, M. (2025) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-025-04047-7 · Cited by 22 · see citing works
Wei, Y., Zhang, D., Shi, H., Qian, H., Chen, H., Zeng, Q., Jin, F., Ye, Y., Ou, Z., Guo, M., et al. (2023) · Genes & Diseases · doi:10.1016/j.gendis.2023.06.013 · Cited by 22 · see citing works
Hypoxia-Inducible Factor in Renal Cell Carcinoma: From Molecular Insights to Targeted Therapies
Roviello, G., Aquino, I. D. G., Vascotto, I. A., Venturi, G., D’Angelo, A., Winchler, C., Guarino, A., Cacioppo, S., Modesti, M., Mela, M. M., et al. (2024) · Genes · doi:10.3390/genes16010006 · Cited by 23 · see citing works
Huang, M., Yang, S., Tai, W., Zhang, L., Zhou, Y., Cho, W. C. S., Chan, L., & Wong, S. C. C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24108720 · Cited by 19 · see citing works
Rashid, M. M., Corbin, B. A., Jella, P. K., Ortiz, C. J., Samee, M. A. H., Pautler, R. G., & Allen, M. J. (2022) · Journal of the American Chemical Society · doi:10.1021/jacs.2c10373 · Cited by 18 · see citing works
Chen, H.-Y., Lin, C., Wu, S.-C., Yang, Z., Chiang, Y., Huang, K., Wang, K.-L., Ali, M. K., Shieh, T., Chang, H., et al. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115533 · Cited by 16 · see citing works
Nanoparticle-Based Immunotherapy for Reversing T-Cell Exhaustion
Li, F., Wang, Y. J., Chen, D., & Du, Y. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25031396 · Cited by 16 · see citing works
Tian, J., Wan, S., Yang, Z., Wang, M., Zhou, W., Wo, G., Fu, S.-P., Zheng, S., Zhou, G., Hu, X., et al. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202400030 · Cited by 16 · see citing works
Interactions between glioblastoma and myeloid cells
Li, Y., Chen, Y., Cai, K., Qin, Y., Wang, X., Zhang, B., Shi, L., He, Z., Wang, J., Long, J., et al. (2025) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1632122 · Cited by 15 · see citing works
Xiang, G., Cui, Y., Wang, P., Feng, Y., Zhang, C., Lou, J., & Zhou, X. (2025) · Journal of Nanobiotechnology · doi:10.1186/s12951-025-03766-4 · Cited by 15 · see citing works
Chen, Z., He, Q., Qian, R., Cai, J., Wang, Z., Zhou, X., Zhang, X., Wang, Q., Si, H., Li, J., et al. (2025) · Advanced Functional Materials · doi:10.1002/adfm.202502807 · Cited by 14 · see citing works
Associations between HIFs and tumor immune checkpoints: mechanism and therapy
Liu, J., Jiang, Y., Chen, L., Qian, Z., & Zhang, Y. (2024) · Discover Oncology · doi:10.1007/s12672-023-00836-7 · Cited by 13 · see citing works
Nazari, A., Osati, P., Fakhr, S. S., Faghihkhorasani, F., Ghanaatian, M., Faghihkhorasani, F., Rezaei‐Tazangi, F., Far, N. P., Shourideh, A., Ebrahimi, N., et al. (2024) · Antioxidants and Redox Signaling · doi:10.1089/ars.2023.0491 · Cited by 13 · see citing works
Wang, Z., Wang, M., Chen, Q., Wang, M., Li, F., Lv, L., Wen, Z., Xu, Z., Yang, Y., Bi, C., et al. (2025) · Advanced Science · doi:10.1002/advs.202504729 · Cited by 13 · see citing works
From immune exclusion to exhaustion: tumor microenvironment drives therapy response
Maletin, N. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1785587 · Cited by 13 · see citing works
Kciuk, M., Wanke, K., Kruczkowska, W., Marciniak, B., & Kontek, R. (2025) · Molecules · doi:10.3390/molecules30132686 · Cited by 14 · see citing works
Ao, K., Sun, Z., Hao, Y., Qin, J., Xu, C., Wen, X., Yang, Z., Li, L., Gan, S., Chen, X., et al. (2025) · ACS Central Science · doi:10.1021/acscentsci.5c00812 · Cited by 13 · see citing works
Hypoxic microenvironment in cancer: role in metabolic reprogramming
Sureka, N., Maheshwari, R., Agravat, A., Singhal, S., Zaman, S., Rishi, B., Siraj, F., Zaheer, S., & Misra, A. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1771365 · Cited by 11 · see citing works
Wang, D., Liu, X., Li, M., & Ning, J. (2023) · Molecular Carcinogenesis · doi:10.1002/mc.23648 · Cited by 12 · see citing works
Abdallah, F. M., Ghoneim, A. I., Abd-Alhaseeb, M. M., Abdel-Raheem, I. T., & Helmy, M. W. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117468 · Cited by 11 · see citing works
Multiple signaling pathways in the frontiers of lung cancer progression
Liu, H., Zhou, D., Ou, Y., Chen, S., Long, Y., Yuan, T., Li, Y., & Tan, Y. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1593793 · Cited by 11 · see citing works
Characterization of Exhausted T Cell Signatures in Pan-Cancer Settings
Juthi, R. T., Sazed, S. A., Mareboina, M., Zaravinos, A., & Georgakopoulos‐Soares, I. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26052311 · Cited by 10 · see citing works
Ginsenosides: Allies of gastrointestinal tumor immunotherapy
Feng, Y., Ma, F., Wu, E., Cheng, Z., Wang, Z., Li, Y., & Zhang, J. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.922029 · Cited by 10 · see citing works
Taghizadeh‐Hesary, F., Ghadyani, M., Kashanchi, F., & Behnam, B. (2024) · Cancers · doi:10.3390/cancers16173044 · Cited by 9 · see citing works
Li, J., Ma, Y., Wu, Q., Ping, P., Li, J., & Xu, X. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1488730 · Cited by 9 · see citing works
Devi, D., Sharma, K., Khan, T., Rani, H., Rana, R., Sharma, H., Kaur, P., Prajapati, L., Rizwan, A., Allieu, M., et al. (2025) · Pathology - Research and Practice · doi:10.1016/j.prp.2025.156271 · Cited by 9 · see citing works
Xue, J., Zhang, L., Zhang, K., Wu, Y., Zhou, K., & Lü, X. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1697056 · Cited by 9 · see citing works
Jeknić, S., Kudo, T., Song, J. J., & Covert, M. W. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.104599 · Cited by 9 · see citing works
Shutting off the fuel supply to target metabolic vulnerabilities in multiple myeloma
Rana, P. S., Goparaju, K., & Driscoll, J. J. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1141851 · Cited by 10 · see citing works
Recent advances in immunotherapy for gliomas: overcoming barriers and advancing precision strategies
Jabri, A., Mhannayeh, A., Taftafa, B., Alsharif, M., Sibai, D., Alsharif, R., Abbad, T., Elsalti, A., Ahmed, Z., Salma, J., et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1690464 · Cited by 8 · see citing works
Lu, L., Johnson, C. H., Khan, S. A., & Irwin, M. (2026) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2026.01.004 · Cited by 8 · see citing works
Montecchi, T., Nannini, G., Tommaso, D. D., Cassioli, C., Coppola, F., Ringressi, M. N., Carraro, F., Naldini, A., Taddei, A., Marotta, G., et al. (2024) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-023-03614-0 · Cited by 7 · see citing works
Li, C., Xue, Y., Yinwang, E., & Ye, Z. (2025) · Cancer Reports · doi:10.1002/cnr2.70044 · Cited by 7 · see citing works
Noda, Y., Atsumi, N., Nakaya, T., Iwai, H., & Tsuta, K. (2025) · Head and Neck Pathology · doi:10.1007/s12105-025-01798-8 · Cited by 7 · see citing works
Yang, S., Liu, Y., Pei, Y., & Qian, Z. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.139318 · Cited by 6 · see citing works
Zhan, T., Feng, X., Huang, H., Zhan, J.-C., Liu, X.-K., & Cheng, Q. (2025) · World Journal of Gastrointestinal Oncology · doi:10.4251/wjgo.v17.i9.108649 · Cited by 8 · see citing works
Abadi, R. N. S., Abadi, Z., & Hooshmand, S. (2025) · Molecular Biology Reports · doi:10.1007/s11033-025-11367-5 · Cited by 6 · see citing works
Fu, X., Zhang, H., Liu, W., Wu, T.-T., & Zheng, Y.-Z. (2026) · Materials Today Bio · doi:10.1016/j.mtbio.2026.102956 · Cited by 6 · see citing works
Ranjbar, A., Soltanshahi, M., Taghiloo, S., & Asgarian‐Omran, H. (2023) · Iranian journal of pharmaceutical research · doi:10.5812/ijpr-140507 · Cited by 6 · see citing works
Du, J., Chu-ting, Z., Li, T., & Li, Y. (2024) · World Journal of Hepatology · doi:10.4254/wjh.v16.i12.1371 · Cited by 6 · see citing works
Li, P., Dong, Z., Jiang, Q., Yu, C., Liu, Y., Yuan, R., Qiu, Y., Meng, T., Hu, F., & Yuan, H. (2026) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.114406 · Cited by 6 · see citing works
Song, G., Xue, S., Zhu, Y., Wu, C., & Ji, X. (2024) · BMC Pharmacology and Toxicology · doi:10.1186/s40360-024-00828-5 · Cited by 6 · see citing works
Myeloid metabolism and its role in immunotherapy of cancer
Garlatti, V., Consonni, F. M., Ballerini, G., Incerti, M., Balboni, A., Cassatella, M. A., & Sica, A. (2025) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2025-012127 · Cited by 5 · see citing works
PD-L1 and HIF-2α Upregulation in Head and Neck Paragangliomas after Embolization
Fischer, A., Macciò, U., Wang, K., Friemel, J., Broglie, M. A., Vetter, D., Lehmann, K., Reul, A., Robledo, M., Hantel, C., et al. (2023) · Cancers · doi:10.3390/cancers15215199 · Cited by 5 · see citing works
Uchihara, M., Tanabe, A., Kojima, Y., Shimoi, T., Maeshima, A. M., Umamoto, K., Shimomura, A., Shimizu, C., Yamazaki, Y., Nakamura, E., et al. (2024) · Cancers · doi:10.3390/cancers16122191 · Cited by 5 · see citing works
The Illustration of Altered Glucose Dependency in Drug-Resistant Cancer Cells
Bishayee, K., Lee, S.-H., & Park, Y. S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241813928 · Cited by 5 · see citing works
Yu, X., He, Y., Zhong, J., Li, Y., Zhu, Y., Chen, Y., Yin, J., Yuan, Z., & Yin, P. (2026) · Materials Today Bio · doi:10.1016/j.mtbio.2026.102824 · Cited by 4 · see citing works
Pei, W.-B., Lei, Z., Xie, F.-Q., Chen, P., Su, Y.-C., Qin, Y.-S., Li, J., Shen, Q.-W., Ma, M., Chun-yi, G., et al. (2026) · Acta Pharmacologica Sinica · doi:10.1038/s41401-025-01728-y · Cited by 4 · see citing works
Rodríguez-Lara, V., Cortés-Ramírez, G., Angeles-Torres, I. A., Rodríguez‐Cid, J. R., Pedraza-Reyes, S. M., Ávila-Costa, M. R., Ordóñez-Librado, J. L., & Cerbón, M. A. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1602579 · Cited by 4 · see citing works
Co, I., Yu, C.-W., Lamorte, S., Ciudad, M., Landon-Brace, N., Cadavid, J. L., Xia, Z., Fomina, A., Nurse, M., McGaha, T., et al. (2023) · bioRxiv · doi:10.1101/2023.07.13.548899 · Cited by 2 · see citing works
Liu, Y., Yang, X., Qin, M., Chen, W., Liu, C., Jiang, W., Wang, Y., Tan, S., Sun, H., Chen, J., et al. (2026) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2026.121554 · Cited by 3 · see citing works
Hypoxia-induced PD-L1 expression and modulation of muscle stem cell allograft rejection
Raiten, J., Abd, G. M., Handelsman, S., Patel, H. V., Ku, J. C., Parsons, A. M., Wassink, J. L., Hayes, S. L., Overbay, J., & Li, Y. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1471563 · Cited by 3 · see citing works
MicroRNA-223: a key regulator of liver tumour microenvironment
Avila, M. A. (2023) · Gut · doi:10.1136/gutjnl-2022-329322 · Cited by 3 · see citing works
Oxygen-carrying nanovaccine potentiates cancer immunotherapy for heterogeneous solid tumors
Tian, J., Yang, Z., Wan, S., Shou, C., Zhang, L., Zhao, Y., Chen, S., Huang, K., Zhao, H., Song, X., et al. (2026) · Materials Today Bio · doi:10.1016/j.mtbio.2026.102875 · Cited by 2 · see citing works
Xia, J., & Zhai, B. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1699202 · Cited by 2 · see citing works
Therapeutic potential for coxib-nitric oxide releasing hybrids in cancer treatment
Giordani, A., Poce, G., Consalvi, S., Maramai, S., Saletti, M., Rossi, A., Patrignani, P., Biava, M., & Anzini, M. (2023) · Elsevier eBooks · doi:10.1016/b978-0-443-13342-8.00009-0 · Cited by 2 · see citing works
Chi, Z.-C. (2025) · World Chinese Journal of Digestology · doi:10.11569/wcjd.v33.i1.11 · Cited by 1 · see citing works
Li, W., Wei, J., Zhang, P., Cheng, M., Xu, M., Zhu, L., & Liu, M. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1625273 · Cited by 1 · see citing works
Shao, L., & Chen, L. (2025) · New cell · doi:10.61958/nchf9858 · Cited by 1 · see citing works
Whelan, G., & Neves, K. B. (2026) · British Journal of Pharmacology · doi:10.1111/bph.70378 · Cited by 1 · see citing works
Nanodynamic Therapy in Colorectal Cancer: Engineering Precision Immunotherapy and Multimodal Synergy
Wang, F., Zhang, Z., Chen, J., Qian, L., Chen, B., Zhai, L., Zhao, J., Chen, T., Zhou, J., Gou, K., et al. (2026) · International Journal of Nanomedicine · doi:10.2147/ijn.s598076 · Cited by 1 · see citing works
Flexible Dual-Apt Scaffolds Reveal gPD-L1-sEVs in Breast Cancer
Qiu, X., Yang, F., Guo, X., Xu, P., Wang, X., Lv, L., Xie, J., Yu, Z., Li, P., Xiao, H., et al. (2026) · Analytical Chemistry · doi:10.1021/acs.analchem.6c01173 · Cited by 1 · see citing works
Li, Q., Huo, Y., Zhu, X., Cheng, Z., Sun, Y., Jin, S., Sun, M., Zhang, H., Wu, X., & Jin, Y. (2026) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.6c00191 · Cited by 1 · see citing works
Chen, Y. (2023) · Frontiers in Medical Science Research · doi:10.25236/fmsr.2023.051103 · Cited by 1 · see citing works
Miyata, S., Ishii, T., & Kitanaka, S. (2023) · Preprints.org · doi:10.20944/preprints202305.1300.v1 · Cited by 1 · see citing works
Ulloa-Navas, M. J., Luo, Y., Sanchez-Garavito, J. E., Qie, Y., Jones, V. K., Brooks, M., Aramburu-Berckemeyer, M. M., Hundal, T., Gadd, M. E., Gomez-Palmero, C., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.11.22.624897 · Cited by 1 · see citing works
Research Progress on Shengxian Decoction in the Treatment of Non-Small Cell Lung Cancer
Liao, H., & Zhu, J. (2024) · Journal of Contemporary Medical Practice · doi:10.53469/jcmp.2024.06(12).18
苗, 舜. (2025) · Advances in Clinical Medicine · doi:10.12677/acm.2025.1551481
Human Cytomegalovirus-Induced Immune Tolerance in Glioma
Baba, R. E., & Herbein, G. (2025) · Current Clinical Microbiology Reports · doi:10.1007/s40588-025-00250-3
- Authors
- Shurin, M. R., & Umansky, V.
- Affiliations
- University of Pittsburgh Medical Center (US)
- German Cancer Research Center (DE)
- Corresponding author
- Shurin, Michael R.
- Venue
- Journal of Clinical Investigation
- Published
- 2022-05-02
- Volume
- 132
- Issue
- 9
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC9057611
- OpenAlex
- W4225246674
- Semantic Scholar
- a20a1dd856629f2de755ae6db054bceeadf62ed8
- Cited by
- 113
- References
- 26
- Citations by year
- 2026: 26 · 2025: 27 · 2024: 31 · 2023: 24 · 2022: 5
- FWCI
- 9.15
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Clinical Investigation (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- University of Pittsburgh
- Deutsches Krebsforschungszentrum
- Universität Heidelberg
- National Cancer Institute (P30CA047904)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Keywords
- hypoxia-inducible factor, HIF-1α, PD-L1, PD-1/PD-L1 axis, tumor hypoxia, HIF inhibitors, immune checkpoint inhibitors, cancer immunotherapy, tumor immune evasion, treatment resistance, carcinogenesis, metastasis
- MeSH terms
- Hypoxia, Humans, Ligands, Neoplasms, Apoptosis, B7-H1 Antigen, Programmed Cell Death 1 Receptor, Carcinogenesis
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