Cited by 218Adenosine and Purinergic SignalingCancer Immunotherapy and BiomarkersBiochemical and Molecular Research

The DOI matches its Crossref record; 82 of the 82 references it cites were found in a registry or an index.

Hostile, Hypoxia–A2-Adenosinergic Tumor Biology as the Next Barrier to Overcome for Tumor Immunologists

Open access

Sitkovsky, Michail V., Hatfield, Stephen, Abbott, Robert, Belikoff, Bryan, Lukashev, Dmitriy, Ohta, Akio·2014·Cancer Immunology Research

DOI 10.1158/2326-6066.cir-14-0075PMC PMC4331061

Open this paper in CoChat — free account Open PDF

Abstract

Hypoxia-driven, A2A adenosine receptor (A2AR)–mediated (hypoxia–A2-adenosinergic), T-cell–autonomous immunosuppression was first recognized as critical and nonredundant in protecting normal tissues from inflammatory damage and autoimmunity. However, this immunosuppressive mechanism can be highjacked by bacteria and tumors to provide misguided protection for pathogens and cancerous tissues. Inhibitors of the hypoxia–A2-adenosinergic pathway represent a conceptually novel type of immunologic coadjuvants that could be combined with cancer vaccines, adoptive cell transfer, and/or blockade of negative immunologic regulators to further prolong patient survival and to minimize treatment-related side effects. In support of this approach are preclinical studies and findings that some human cancers are resistant to chemotherapies and immunotherapies due to the tumor-generated extracellular adenosine and A2AR on antitumor T and natural killer (NK) cells. Among the coadjuvants are (i) antagonists of A2AR, (ii) extracellular adenosine-degrading drugs, (iii) inhibitors of adenosine generation by CD39/CD73 ectoenzymes, and (iv) inhibitors of hypoxia–HIF-1α signaling. Combining these coadjuvants with CTLA-4 and/or PD-1 blockade is expected to have additive or even synergistic effects of targeting two different antitumor protective mechanisms. It is expected that even after multicombinatorial blockade of negative immunologic regulators, the antitumor T and NK cells would still be vulnerable to inhibition by hypoxia and A2AR. Yet to be tested is the potential capacity of coadjuvants to minimize the side effects of CTLA-4 and/or PD-1 blockade by decreasing the dose of blocking antibodies or by eliminating the need for dual blockade. Cancer Immunol Res; 2(7); 598–605. ©2014 AACR.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1158/2326-6066.cir-14-0075

Cites

82 of 82 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

2 retracted

Hypoxia-Inducible Factor-1α–Dependent Protection from Intestinal Ischemia/Reperfusion Injury Involves Ecto-5′-Nucleotidase (CD73) and the A2B Adenosine Receptor
Hart, M. L., Grenz, A., Gorzolla, I. C., Schittenhelm, J., Dalton, J. H., & Eltzschig, H. K. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.0903617 · Cited by 120
Retracted
Retraction: Hypoxia-Inducible Factor-1α–Dependent Protection from Intestinal Ischemia/Reperfusion Injury Involves Ecto-5′-Nucleotidase (CD73) and the A2B Adenosine Receptor
Hart, M. L., Gorzolla, I. C., Schittenhelm, J., Dalton, J. H., & Eltzschig, H. K. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1700997 · Cited by 116
Retracted
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., Gonzalez, R., Robert, C., Schadendorf, D., Hassel, J. C., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1003466 · Cited by 15,155
The blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838
Safety, activity, and immune correlates of anti–PD-1 antibody in cancer
Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., Powderly, J. D., Carvajal, R. D., Sosman, J. A., Atkins, M. B., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200690 · Cited by 12,628
Nivolumab plus Ipilimumab in Advanced Melanoma
Wolchok, J. D., Kluger, H., Callahan, M. K., Postow, M. A., Rizvi, N. A., Lesokhin, A. M., Segal, N. H., Ariyan, C. E., Gordon, R.-A., Reed, K., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1302369 · Cited by 4,230
Hypoxia-inducible factors in physiology and medicine
Semenza, G. L. (2012) · Cell · doi:10.1016/j.cell.2012.01.021 · Cited by 3,645
Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression
Deaglio, S., Dwyer, K. M., Gao, W., Friedman, D. J., Usheva, A., Erat, A., Chen, J., Enjyoji, K., Linden, J. M., Oukka, M., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20062512 · Cited by 2,613
Adoptive immunotherapy for cancer: harnessing the T cell response
Restifo, N. P., Dudley, M. E., & Rosenberg, S. A. (2012) · Nature Reviews Immunology · doi:10.1038/nri3191 · Cited by 1,688
Combining immunotherapy and targeted therapies in cancer treatment
Vanneman, M. W., & Dranoff, G. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3237 · Cited by 1,627

Show all 82 references

Sorted by citations

Items 101–200 of 218

Biomimetic Cell-Derived Nanoparticles: Emerging Platforms for Cancer Immunotherapy
Hu, T., Huang, Y., Liu, J., Shen, C., Wu, F., & He, Z. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15071821 · Cited by 37
A 2A adenosine receptors control pancreatic dysfunction in high‐fat‐diet‐induced obesity
Csóka, B., Törő, G., Vindeirinho, J., Varga, Z. V., Koscsó, B., Németh, Z. H., Kókai, E., Antonioli, L., Suleiman, M., Marchetti, P., et al. (2017) · The FASEB Journal · doi:10.1096/fj.201700398r · Cited by 36
Purinergic Signalling in Parkinson’s Disease: A Multi-target System to Combat Neurodegeneration
Tóth, A., Antal, Z., Bereczki, D., & Sperlágh, B. (2019) · Neurochemical Research · doi:10.1007/s11064-019-02798-1 · Cited by 34
Protein kinase inhibitor ceritinib blocks ectonucleotidase CD39 – a promising target for cancer immunotherapy
Schäkel, L., Mirza, S., Winzer, R., Lopez, V., Idris, R. M., Al-Hroub, H., Pelletier, J., Sévigny, J., Tolosa, E., & Müller, C. E. (2022) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2022-004660 · Cited by 34
Mechanistic Justifications of Systemic Therapeutic Oxygenation of Tumors to Weaken the Hypoxia Inducible Factor 1α-Mediated Immunosuppression
Hatfield, S. M., Halpin-Veszeleiova, K., Steingold, J., Sethuraman, J., & Sitkovsky, M. V. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-12734-3_8 · Cited by 32
Self-citation
Immune Checkpoint Blockade for Prostate Cancer: Niche Role or Next Breakthrough?
de Almeida, D. V. P., Fong, L. H., Rettig, M. B., & Autio, K. A. (2020) · American Society of Clinical Oncology Educational Book · doi:10.1200/edbk_278853 · Cited by 34
Adenosine Signaling in the Tumor Microenvironment
Antonioli, L., Fornai, M., Pellegrini, C., D’Antongiovanni, V., Turiello, R., Morello, S., Haskó, G., & Blandizzi, C. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-47189-7_9 · Cited by 32
Disruption of adenosine 2A receptor improves the anti-tumor function of anti-mesothelin CAR T cells both in vitro and in vivo
Liu, G., Zhang, Q., Liu, G., Li, D., Zhang, L., Gu, Z., Tian, H., Zhang, Y., & Tian, X. (2021) · Experimental Cell Research · doi:10.1016/j.yexcr.2021.112886 · Cited by 32
Oxygenation to improve cancer vaccines, adoptive cell transfer and blockade of immunological negative regulators
Hatfield, S. M., & Sitkovsky, M. (2015) · OncoImmunology · doi:10.1080/2162402x.2015.1052934 · Cited by 31
Self-citation
Hypoxic tumor microenvironment: Destroyer of natural killer cell function
Zhang, Y., Guo, F., & Wang, Y. (2024) · Chinese Journal of Cancer Research · doi:10.21147/j.issn.1000-9604.2024.02.04 · Cited by 32
CD73; a key ectonucleotidase in the development of breast cancer: Recent advances and perspectives
Soleimani, A., Taghizadeh, E., Shahsavari, S., Amini, Y., Rashidpour, H., Azadian, E., Jafari, A., Parizadeh, M. R., Mashayekhi, K., Soukhtanloo, M., et al. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.28187 · Cited by 28
Linking Transcriptomic and Imaging Data Defines Features of a Favorable Tumor Immune Microenvironment and Identifies a Combination Biomarker for Primary Melanoma
Gartrell, R. D., Chen, A., Rizk, E. M., Marks, D. K., Bogardus, M. H., Hart, T. D., Silverman, A. M., Bayan, C.-A. Y., Finkel, G. G., Barker, L. W., et al. (2020) · Cancer Research · doi:10.1158/0008-5472.can-19-2039 · Cited by 30
Blocking Migration of Polymorphonuclear Myeloid-Derived Suppressor Cells Inhibits Mouse Melanoma Progression
Groth, C., Arpinati, L., Shaul, M. E., Winkler, N., Diester, K., Gengenbacher, N., Weber, R., Arkhypov, I., Lasser, S., Petrova, V., et al. (2021) · Cancers · doi:10.3390/cancers13040726 · Cited by 30
Targeting the purinergic pathway in breast cancer and its therapeutic applications
de Araújo, J. B., Kerkhoff, V. V., Maciel, S. F. V. D. O., & Silva, D. T. D. R. E. (2021) · Purinergic Signalling · doi:10.1007/s11302-020-09760-9 · Cited by 33
Bispecific T-Cell Engagers and Chimeric Antigen Receptor T-Cell Therapies in Glioblastoma: An Update
Alsajjan, R., & Mason, W. P. (2023) · Current Oncology · doi:10.3390/curroncol30090619 · Cited by 32
The Adenosine System at the Crossroads of Intestinal Inflammation and Neoplasia
D’Antongiovanni, V., Fornai, M., Pellegrini, C., Benvenuti, L., Blandizzi, C., & Antonioli, L. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21145089 · Cited by 27
The Sabotaging Role of Myeloid Cells in Anti‐Angiogenic Therapy: Coordination of Angiogenesis and Immune Suppression by Hypoxia
Li, C., Liu, T., Bazhin, A. V., & Yang, Y. (2016) · Journal of Cellular Physiology · doi:10.1002/jcp.25726 · Cited by 29
The CD73/Ado System—A New Player in RT Induced Adverse Late Effects
de Leve, S., Wirsdörfer, F., & Jendrossek, V. (2019) · Cancers · doi:10.3390/cancers11101578 · Cited by 26
How Cells Communicate with Each Other in the Tumor Microenvironment: Suggestions to Design Novel Therapeutic Strategies in Cancer Disease
Zefferino, R., Piccoli, C., Gioia, S. D., Capitanio, N., & Conese, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052550 · Cited by 26
Advanced Acral Melanoma Therapies: Current Status and Future Directions
Zhang, Y., Lan, S., & Wu, D. (2022) · Current Treatment Options in Oncology · doi:10.1007/s11864-022-01007-6 · Cited by 26
Application prospect of calcium peroxide nanoparticles in biomedical field
Wu, X., Xu, H., Guo, Y., Liu, Q., Sun, R., Wen, Z., & Dai, C. (2023) · REVIEWS ON ADVANCED MATERIALS SCIENCE · doi:10.1515/rams-2022-0308 · Cited by 28
Oxygenation and A2AR blockade to eliminate hypoxia/HIF-1α-adenosinergic immunosuppressive axis and improve cancer immunotherapy
Halpin-Veszeleiova, K., & Hatfield, S. M. (2020) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2020.07.005 · Cited by 31
Self-citation
Potassium channels of T lymphocytes take center stage in the fight against cancer
Conforti, L. (2017) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-016-0202-5 · Cited by 25
Current perspectives and trends of CD39-CD73-eAdo/A2aR research in tumor microenvironment: a bibliometric analysis
Huang, T., Ren, X., Tang, X., Wang, Y., Ji, R., Guo, Q., Ma, Q., Zheng, Y., Hu, Z., & Zhou, Y. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1427380 · Cited by 28
Oxygen therapeutic agents to target hypoxia in cancer treatment
Spiess, B. D. (2020) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2020.09.009 · Cited by 20
Metabolic interventions combined with CTLA-4 and PD-1/PD-L1 blockade for the treatment of tumors: mechanisms and strategies
Liao, L., Xu, H., Zhao, Y., & Zheng, X. (2023) · Frontiers of Medicine · doi:10.1007/s11684-023-1025-7 · Cited by 22
αβ TCR-Mediated Recognition: Relevance to Tumor-Antigen Discovery and Cancer Immunotherapy
Reinherz, E. L. (2015) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-15-0042 · Cited by 23
Oxygen-carrying nanoemulsions and respiratory hyperoxia eliminate tumor hypoxia–induced immunosuppression
Halpin-Veszeleiova, K., Mallouh, M. P., Williamson, L. M., Apro, A. C., Botticello-Romero, N. R., Bahr, C., Shin, M., Ward, K. M., Rosenberg, L., Ritov, V. B., et al. (2025) · JCI Insight · doi:10.1172/jci.insight.174675 · Cited by 28
Self-citation
Current Adenosinergic Therapies: What Do Cancer Cells Stand to Gain and Lose?
Kotulová, J., Hajdúch, M., & Džubák, P. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222212569 · Cited by 21
A2A Receptor Contributes to Tumor Progression in P2X7 Null Mice
Marchi, E. D., Pegoraro, A., Turiello, R., Virgilio, F. D., Morello, S., & Adinolfi, E. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.876510 · Cited by 21
The Role of Tumor-Derived Exosomes (TEX) in Shaping Anti-Tumor Immune Competence
Whiteside, T. L. (2021) · Cells · doi:10.3390/cells10113054 · Cited by 21
Cytokine-Induced Killer Cells Express CD39, CD38, CD203a, CD73 Ectoenzymes and P1 Adenosinergic Receptors
Horenstein, A. L., Chillemi, A., Zini, R., Quarona, V., Bianchi, N., Manfredini, R., Gambari, R., Malavasi, F., & Ferrari, D. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00196 · Cited by 19
The diverse effects of cisplatin on tumor microenvironment: Insights and challenges for the delivery of cisplatin by nanoparticles
Meng, X., Ma, F., & Yu, D. (2023) · Environmental Research · doi:10.1016/j.envres.2023.117362 · Cited by 19
Identification of novel thiazolo[5,4-d]pyrimidine derivatives as human A1 and A2A adenosine receptor antagonists/inverse agonists
Varano, F., Catarzi, D., Falsini, M., Vincenzi, F., Pasquini, S., Varani, K., & Colotta, V. (2018) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2018.05.048 · Cited by 18
Prostaglandin E2-mediated adenosinergic effects on CD14+cells: Self-amplifying immunosuppression in cancer
Al-Taei, S., Salimu, J., Spary, L. K., Clayton, A., Lester, J. F., & Tabi, Z. (2017) · OncoImmunology · doi:10.1080/2162402x.2016.1268308 · Cited by 17
Controlling Pericellular Oxygen Tension in Cell Culture Reveals Distinct Breast Cancer Responses to Low Oxygen Tensions
Rogers, Z. J., Colombani, T., Khan, S., Bhatt, K., Nukovic, A., Zhou, G., Woolston, B. M., Taylor, C. T., Gilkes, D. M., Slavov, N., et al. (2024) · Advanced Science · doi:10.1002/advs.202402557 · Cited by 20
Role of adenosine in tumor progression: focus on A2B receptor as potential therapeutic target
Sorrentino, C., & Morello, S. (2017) · Journal of Cancer Metastasis and Treatment · doi:10.20517/2394-4722.2017.29 · Cited by 17
Anticoagulation therapy promotes the tumor immune-microenvironment and potentiates the efficacy of immunotherapy by alleviating hypoxia
Choi, J. U., Lee, N. K., Seo, H., Chung, S. W., Al-Hilal, T. A., Park, S. J., Kweon, S., Min, N., Kim, S. K., Ahn, S.-H., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-002332 · Cited by 17
Istradefylline protects from cisplatin-induced nephrotoxicity and peripheral neuropathy while preserving cisplatin antitumor effects
Dewaeles, E., Carvalho, K., Fellah, S., Sim, J., Boukrout, N., Caillierez, R., Ramakrishnan, H., der Hauwaert, C. V., Shankara, J. V., Martin, N., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci152924 · Cited by 22
Breaking hypoxic barrier: Oxygen-supplied nanomaterials for enhanced T cell-mediated tumor immunotherapy
Xiang, S., Zhan, H., Zhan, J., Li, X., Lin, X., & Sun, W. (2025) · International Journal of Pharmaceutics X · doi:10.1016/j.ijpx.2025.100400 · Cited by 16
The Promise of Targeting Hypoxia to Improve Cancer Immunotherapy: Mirage or Reality?
Janji, B., & Chouaı̈b, S. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.880810 · Cited by 18
Sufficient numbers of anti-tumor T cells is a condition of maximal efficacy of anti-hypoxia-A2-adenosinergic drugs during cancer immunotherapy
Sitkovsky, M. V. (2020) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2020.07.011 · Cited by 14
Self-citation
Rethinking the adenosine-A2AR checkpoint: implications for enhancing anti-tumor immunotherapy
Helms, R. S., & Powell, J. D. (2020) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2020.07.003 · Cited by 14
Hybrid prodrug nanoassembly for hypoxia-triggered immunogenic chemotherapy and immune modulation
Zhang, B., Qin, C., Wang, X., Shen, C., Li, S., Liu, T., Li, W., Chen, Z., Wang, Y., Liu, L., et al. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.01.008 · Cited by 14
Recent Progress of Adenosine Receptor Modulators in the Development of Anticancer Chemotherapeutic Agents
Marwein, S., Mishra, B., De, U. C., & Acharya, P. C. (2019) · Current Pharmaceutical Design · doi:10.2174/1381612825666190716141851 · Cited by 14
Insights from Clinical Trials on A 2A Adenosine Receptor Antagonists for Cancer Treatment
Deb, P. K., Maity, P., Sarkar, B., Venugopala, K. N., Tekade, R. K., & Batra, S. (2025) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.5c00057 · Cited by 14
Abscopal Effect and Drug-Induced Xenogenization: A Strategic Alliance in Cancer Treatment?
Franzese, O., Torino, F., Giannetti, E., Cioccoloni, G., Aquino, A., Faraoni, I., Fuggetta, M. P., Vecchis, L. D., Giuliani, A., Kaina, B., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910672 · Cited by 12
Antibody-Based Therapeutics for the Treatment of Renal Cell Carcinoma: Challenges and Opportunities
Mahmoud, A. M., Nabavizadeh, R., Pessoa, R. R., Garg, I. D., Orme, J. J., Costello, B. A., Cheville, J. C., & Lucien, F. (2023) · The Oncologist · doi:10.1093/oncolo/oyac263 · Cited by 13
Cd39 (Entpd1) in Tumors: A Potential Therapeutic Target and Prognostic Biomarker
Li, C., Zhang, L., Jin, Q., Jiang, H., & Wu, C. (2023) · Biomarkers in Medicine · doi:10.2217/bmm-2023-0202 · Cited by 13
A biomimetic nanoplatform mediates hypoxia-adenosine axis disruption and PD-L1 knockout for enhanced MRI-guided chemodynamic-immunotherapy
Sun, M., Ni, C., Li, A., Liu, J., Guo, H., Xu, F., Li, K., Cao, X., Shi, X., & Guo, R. (2025) · Acta Biomaterialia · doi:10.1016/j.actbio.2025.06.021 · Cited by 12
Tumor site-directed A1R expression enhances CAR T cell function and improves efficacy against solid tumors
Sek, K., Chen, A. X. Y., Cole, T., Armitage, J. D., Tong, J., Yap, K. M., Munoz, I., Dunbar, P. A., Wu, S., van Elsas, M. J., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-59021-9 · Cited by 17
Methylation of the NT5E Gene Is Associated with Poor Prognostic Factors in Breast Cancer
Jeong, Y. J., Oh, H. K., Choi, H. R., & Park, S. H. (2020) · Diagnostics · doi:10.3390/diagnostics10110939 · Cited by 12
Release of adenosine-induced immunosuppression: Comprehensive characterization of dual A2A/A2B receptor antagonist
Dziedzic, K., Węgrzyn, P., Gałȩzowski, M., Bońkowska, M., Grycuk, K., Satała, G., Wiatrowska, K., Wiklik, K., Brzózka, K. D., & Nowak, M. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.107645 · Cited by 12
Molecular Biology of Kidney Cancer
Kaelin, W. G. (2015) · Springer eBooks · doi:10.1007/978-3-319-17903-2_3 · Cited by 12
A2AR eGFP reporter mouse enables elucidation of A2AR expression dynamics during anti-tumor immune responses
Todd, K. L., Lai, J., Sek, K., Huang, Y., Newman, D. M., Derrick, E. B., Koay, H., Nguyen, D. Q., Hoang, T. X., Petley, E. V., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-42734-0 · Cited by 13
Cannabidiol at Nanomolar Concentrations Negatively Affects Signaling through the Adenosine A2A Receptor
Raïch, I., Lillo, J., Ferreiro‐Vera, C., de Medina, V. S., Navarro, G., & Franco, R. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242417500 · Cited by 11
Gene regulation in activated microglia by adenosine A3 receptor agonists: a transcriptomics study
Lillo, A., Serrano‐Marín, J., Lillo, J., Raïch, I., Navarro, G., & Franco, R. (2023) · Purinergic Signalling · doi:10.1007/s11302-022-09916-9 · Cited by 11
Targeting the Adenosinergic Axis in Chronic Lymphocytic Leukemia: A Way to Disrupt the Tumor Niche?
Vaisitti, T., Arruga, F., & Deaglio, S. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19041167 · Cited by 11
Regionally selective cardiovascular responses to adenosine A 2A and A 2B receptor activation
Cooper, S. L., Wragg, E. S., Pannucci, P., Soave, M., Hill, S. J., & Woolard, J. (2022) · The FASEB Journal · doi:10.1096/fj.202101945r · Cited by 10
Therapeutic Targeting of Hypoxia-A2-Adenosinergic Pathway in COVID-19 Patients
Halpin-Veszeleiova, K., & Hatfield, S. M. (2021) · Physiology · doi:10.1152/physiol.00010.2021 · Cited by 10
Self-citation
Knockout of Factor-Inhibiting HIF (Hif1an) in Colon Epithelium Attenuates Chronic Colitis but Does Not Reduce Colorectal Cancer in Mice
Schützhold, V., Gravemeyer, J., Bicker, A., Hager, T., Padberg, C., Schäfer, J., Wrobeln, A., Steinbrink, M., Zeynel, S., Hankeln, T., et al. (2022) · The Journal of Immunology · doi:10.4049/jimmunol.2100418 · Cited by 9
RETRACTED ARTICLE: Molecular and therapeutic effect of CRISPR in treating cancer
Rodrigo, S., Senasinghe, K., & Quazi, S. (2023) · Medical Oncology · doi:10.1007/s12032-022-01930-6 · Cited by 10
Retracted
The adenosine A2A receptor is a therapeutic target in neurological, heart and oncogenic diseases
Franco, R., Lillo, A., Navarro, G., & Reyes‐Resina, I. (2022) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2022.2136570 · Cited by 8
Suppressing the Hypoxia‐Adenosinergic Axis by a Tailored Nanoreactor for Enhanced Photothermal Immunotherapy
Gu, J., Chang, J., Chen, S., Zhi, H., Sun, J., Yin, W., Zhang, T., Zang, J., Zhao, Y., Liu, Y., et al. (2024) · Small Science · doi:10.1002/smsc.202300242 · Cited by 13
Targeting conserved domains of hypoxia-inducible factors for cancer therapy
Salman, S., Huang, T. Y., Hwang, Y., Kumar, A., Datan, E., Wicks, E. E., Cho, E., Lee, S. N., Chen, C. O., Peng, Y., et al. (2026) · The Journal of Experimental Medicine · doi:10.1084/jem.20251009 · Cited by 8
Rational engineering of an improved adenosine deaminase 2 enzyme for weaponizing T-cell therapies
Cox, J. R., Jennings, M. R., Lenahan, C., Manion, M., Courville, S., & Blazeck, J. (2023) · Immuno-Oncology Technology · doi:10.1016/j.iotech.2023.100394 · Cited by 7
Exploring CD39 and CD73 Expression as Potential Biomarkers in Prostate Cancer
Gardani, C. F. F., Pedrazza, E. L., Paz, V. S., Zanirati, G., da Costa, J. C., Andrejew, R., Ulrich, H., Scholl, J. N., Figueiró, F., Rockenbach, L., et al. (2023) · Pharmaceuticals · doi:10.3390/ph16111619 · Cited by 7
Augmentation of tumour perfusion by ultrasound and microbubbles: A preclinical study
Zhang, J., Zhang, Y., Cai, Z., Wei, J., Li, H., Li, P., Dong, X., & Liu, Z. (2023) · Ultrasonics · doi:10.1016/j.ultras.2023.107219 · Cited by 7
Purinergic pathways and their clinical use in the treatment of acute myeloid leukemia
Wang, H., Wei, Y., & Wang, N. (2024) · Purinergic Signalling · doi:10.1007/s11302-024-09997-8 · Cited by 7
The role of CD73 in predicting the response to immunotherapy in head and neck cancer patients
Botticelli, A., Cirillo, A., d’Amati, G., Gioia, C. R. T. D., Corsi, A., Rocca, C. D., Santini, D., Carletti, R., Pisano, A., Polimeni, A., et al. (2024) · Pathology - Research and Practice · doi:10.1016/j.prp.2024.155415 · Cited by 6
CD73: a new immune checkpoint for leukemia treatment
Gao, H., Zhang, T., Li, K., & Li, X. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1486868 · Cited by 6
The Purinergic Landscape of Non-Small Cell Lung Cancer
Hreich, S. J. D., Benzaquen, J., Hofman, P. M., & Vouret‐Craviari, V. (2022) · Cancers · doi:10.3390/cancers14081926 · Cited by 6
Protective and therapeutic potentials of HDL and ApoA1 in COVID-19 elderly and chronic illness patients
ABDEL-HAFEZ, M. A. (2022) · Bulletin of the National Research Centre/Bulletin of the National Research Center · doi:10.1186/s42269-022-00886-x · Cited by 6
Combined cancer immunotherapy based on targeting adenosine pathway and PD-1/PDL-1 axis
Fathi, M., Zarei, A., Moghimi, A., Jalali, P., Salehi, Z., Gholamin, S., & Jadidi‐Niaragh, F. (2024) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2024.2405090 · Cited by 6
Design, development and evaluation of a tritium-labeled radiotracer for ecto-5’-nucleotidase (CD73) – A versatile research tool and diagnostic agent for personalized medicine
Idris, R. M., Al-Hroub, H., Schmies, C. C., Riziki, P., Renn, C., Claff, T., Sylvester, K., Moschütz, S., Reinhardt, J., Deuther‐Conrad, W., et al. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.118115 · Cited by 5
Enzymatic and microenvironmental regulation in adenosine metabolism-mediated immunosuppression
Li, C., Chen, L., Li, Z., Liang, L., & Lou, B. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1739983 · Cited by 6
Harnessing the power of tumor-draining lymph nodes: unveiling predictive biomarkers for immune checkpoint inhibitor
Chen, Z., Yu, J., Zhikun, G., Chen, S., Li, Y., Zhou, Q., & Wang, L. (2025) · Exploration of Targeted Anti-tumor Therapy · doi:10.37349/etat.2025.1002315 · Cited by 4
Modulating CD38 enzymatic activity during antibody-based immunotherapy in multiple myeloma: a basic science perspective
Horenstein, A. L., Frerichs, K. A., Faini, A. C., van de Donk, N. W. C. J., & Malavasi, F. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1769281 · Cited by 4
Adenosine A2AR in viral immune evasion and therapy: unveiling new avenues for treating COVID-19 and AIDS
Atif, M., Alsrhani, A., Naz, F., Ullah, S., Abdalla, A. E., Ullah, M. I., Mazhari, B. B. Z., Eltayeb, L. B., Hamad, İ., & Ejaz, H. (2024) · Molecular Biology Reports · doi:10.1007/s11033-024-09839-1 · Cited by 4
A novel adenosine 2A receptor antagonist HZ-086 enhances the efficiency of immunotherapy and alleviates the acquired resistance to PD-L1 by restoration of T cell functions
Wang, P., Ding, W., Mo, J., Gu, C., Ouyang, S., Peng, K., Zhang, Q., Lu, J., Lu, J., Wang, Y., et al. (2025) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2025.177535 · Cited by 4
High expression of CD73 contributes to poor prognosis of clear-cell renal cell carcinoma by promoting cell proliferation and migration
Zhou, Y., Jiang, D., Chu, X., Yan, M., Qi, H., Wu, X., Tang, Y., & Dai, Y. (2022) · Translational Cancer Research · doi:10.21037/tcr-22-544 · Cited by 5
Targeting adenosine A2A receptors for early intervention of retinopathy of prematurity
Chen, X., Sun, X., Ge, Y., Zhou, X., & Chen, J. (2024) · Purinergic Signalling · doi:10.1007/s11302-024-09986-x · Cited by 4
Biomarker-Driven Immunotherapy for Precision Medicine in Prostate Cancer
Ottini, A., Sepe, P., Beninato, T., Claps, M., Guadalupi, V., Verzoni, E., Giannatempo, P., Baciarello, G., de Braud, F., & Procopio, G. (2021) · Personalized Medicine · doi:10.2217/pme-2021-0079 · Cited by 4
Prognostic impact of CD73/adenosine 2A receptor (A2AR) in renal cell carcinoma and immune microenvironmental status with sarcomatoid changes and rhabdoid features
Takamatsu, D., Kiyozawa, D., Kohashi, K., Kinoshita, F., Toda, Y., Ishihara, S., Eto, M., & Oda, Y. (2023) · Pathology - Research and Practice · doi:10.1016/j.prp.2023.154423 · Cited by 3
Inhibitory effect of adenosine on adaptive antitumor immunity and intervention strategies
Wang, L., Zhang, W., ZHANG, J., Zheng, M., Pan, X., Guo, H., & Ding, L. (2023) · Journal of Zhejiang University (Medical Sciences) · doi:10.3724/zdxbyxb-2023-0263 · Cited by 3
Landscape of targets within nucleoside metabolism for the modification of immune responses
Dunderdale, E. M., & Abt, E. R. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1483769 · Cited by 2
Role of TIGIT in tumor progression and immune evasion
Li, H., Yu, Y., Chen, L., Wu, J., Guo, W., Chen, S., Lyu, W., Wang, L., & Xu, J. (2026) · Journal of Pancreatology · doi:10.1097/jp9.0000000000000245 · Cited by 2
Purinergic signaling and cancer neuroscience
Hu, J.-Q., Zhou, X., Qing-ling, R., & Han, Y. (2026) · Neuropharmacology · doi:10.1016/j.neuropharm.2026.111048 · Cited by 2
The interaction between end-metabolites and immune escape
Zhu, T., & Wang, G. (2022) · Oncology and Translational Medicine · doi:10.1007/s10330-022-0573-3 · Cited by 3
Adenosine A2A Receptor Antagonists in Drug Development
Müller, C. E. (2015) · Current topics in neurotoxicity · doi:10.1007/978-3-319-20273-0_3 · Cited by 2
Cancer Immunotherapy Out of the Gate: The 22nd Annual Cancer Research Institute International Immunotherapy Symposium
Tontonoz, M. J., & Gee, C. E. (2015) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-15-0072 · Cited by 2
Anti-Leukemic Effects Induced by Dendritic Cells of Leukemic Origin from Leukemic Blood Samples Are Comparable under Hypoxic vs. Normoxic Conditions
Doraneh-Gard, F., Amberger, D. C., Amend, C., Weinmann, M., Schwepcke, C., Klauer, L. K., Schutti, O., Hosseini, H., Kraemer, D. M., Rank, A., et al. (2024) · Cancers · doi:10.3390/cancers16132383 · Cited by 2
Development and validation of an LC–MS/MS method for the quantitative analysis of the adenosine A2a receptor antagonist NIR178 and its monohydroxy metabolite in human plasma: Application to clinical pharmacokinetics
Heudi, O., Nathalie, P., Aumonier, C., Wu, S., Hatsis, P., Hurtado, F. K., Picard, F., Winter, S., & Flarakos, J. (2020) · Biomedical Chromatography · doi:10.1002/bmc.4909 · Cited by 2
Chimeric antigen receptor-modified cells for the treatment of solid tumors: First steps in a thousand-mile march
Rafei, H., Başar, R., Rezvani, K., & Daher, M. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-822620-9.00021-5 · Cited by 1
Ectonucleotidases CD39 and CD73 expression levels are independent and inverse predictors of survival in muscle‐invasive bladder cancer
Ledderose, S., Schwenke, J., Eismann, L., Rodler, S., Rudelius, M., & Ledderose, C. (2026) · The Journal of Pathology Clinical Research · doi:10.1002/2056-4538.70102 · Cited by 1
Editorial overview: Cancer 2020 current mechanistic insights into the hypoxia-adenosine-A2A adenosinergic immunosuppressive axis in cancer immunotherapies
Beavis, P. A., & Hatfield, S. M. (2020) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2020.10.012 · Cited by 1
Self-citation
Frontiers of Cancer Diagnostics: From Photoacoustic Chemical Imaging to Cellular Morphodynamics
Folz, J. (2020) · Deep Blue (University of Michigan) · Cited by 1
Manipulating the hypoxic tumour microenvironment to study therapy resistance
Ient, J. (2021) · Research Publications (Maastricht University) · doi:10.26481/dis.20210311jl · Cited by 1
Immune Checkpoint Combinations with Inflammatory Pathway Modulators
DeVito, N. C., Morse, M. A., Hanks, B. A., & Clarke, J. M. (2017) · Current cancer research · doi:10.1007/978-3-319-63757-0_8
The role of hypoxia and adenosine signaling in vaccine design
Abbott, R. K. (2016) · Digital Repository Service (Northeastern University) · doi:10.17760/d20209749
Self-citation

Authors: Sitkovsky, M. V., Hatfield, S., Abbott, R., Belikoff, B., Lukashev, D., & Ohta, A.
Affiliations: Northeastern University (US)
Corresponding author: Sitkovsky, Michail V.
ORCID: Sitkovsky, Michail V.
Hatfield, Stephen
Abbott, Robert
Ohta, Akio
Venue: Cancer Immunology Research
Publisher: American Association for Cancer Research (AACR)
Published: 2014-07-01
Volume: 2
Issue: 7
Pages: 598-605
ISSN: 2326-6066 (ISSN-L)
2326-6074
DOI: 10.1158/2326-6066.cir-14-0075
PMC: PMC4331061
OpenAlex: W2086437277
Cited by: 215
References: 82
Citations by year: 2026: 9 · 2025: 14 · 2024: 13 · 2023: 29 · 2022: 20 · 2021: 26 · 2020: 29 · 2019: 16 · 2018: 17 · 2017: 11 · 2016: 14 · 2015: 14 · 2014: 2
FWCI: 1.64
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Cancer Immunology Research (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Cancer Institute (R01CA111985)
National Institute of General Medical Sciences (R01GM097320)
National Institute of Allergy and Infectious Diseases (U19AI091693)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
Keywords: tumor hypoxia, adenosine A2A receptor, extracellular adenosine, immunosuppression, HIF-1α signaling, CTLA-4 blockade, anti-PD-1 therapy, cancer vaccines, adoptive cell transfer, natural killer cells, tumor immunology
MeSH terms: Humans, Immune Tolerance, Immunotherapy, Neoplasms, T-Lymphocytes, Signal Transduction, Cell Hypoxia, Receptor, Adenosine A2A, Hypoxia-Inducible Factor 1, alpha Subunit

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Hostile, Hypoxia–A2-Adenosinergic Tumor Biology as the Next Barrier to Overcome for Tumor Immunologists

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks