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Loss of IFN-γ Pathway Genes in Tumor Cells as a Mechanism of Resistance to Anti-CTLA-4 Therapy
Open accessAbstract
Antibody blockade of the inhibitory CTLA-4 pathway has led to clinical benefit in a subset of patients with metastatic melanoma. Anti-CTLA-4 enhances T cell responses, including production of IFN-γ, which is a critical cytokine for host immune responses. However, the role of IFN-γ signaling in tumor cells in the setting of anti-CTLA-4 therapy remains unknown. Here, we demonstrate that patients identified as non-responders to anti-CTLA-4 (ipilimumab) have tumors with genomic defects in IFN-γ pathway genes. Furthermore, mice bearing melanoma tumors with knockdown of IFN-γ receptor 1 (IFNGR1) have impaired tumor rejection upon anti-CTLA-4 therapy. These data highlight that loss of the IFN-γ signaling pathway is associated with primary resistance to anti-CTLA-4 therapy. Our findings demonstrate the importance of tumor genomic data, especially IFN-γ related genes, as prognostic information for patients selected to receive treatment with immune checkpoint therapy.
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“Mutations in IFNGR1 and JAK, a component of the IFNγ signaling pathway, have been found in patients presenting resistance to checkpoint inhibitors (Gao et al., 2016; Zaretsky et al., 2016).”
From Protein Barcodes Enable High-Dimensional Single-Cell CRISPR Screens (2018) · cites this paper as Gao et al., 2016
In the citing paper
“These findings are consistent with emerging clinical data correlating resistance to checkpoint inhibitors with mutations in the B2m and IFNγ pathways (Gao et al., 2016; Zaretsky et al., 2016), and with recent genome-wide CRISPR screening data (Patel et al., 2017).”
From Protein Barcodes Enable High-Dimensional Single-Cell CRISPR Screens (2018) · cites this paper as Gao et al., 2016
In the citing paper
“P. distasonis has been shown to enhance immune checkpoint inhibitor-mediated anticancer immunity by inducing the production of IFNγ+CD8+ T cells.53 54”
In the citing paper
“In addition, knockdown of IFNγ-receptor 1 led to impaired antitumor responses with anti-CTLA4 in a murine model of melanoma (159).”
From The Next Decade of Immune Checkpoint Therapy (2021) · cites this paper as [159]
In the citing paper
“Interferon (IFN) signaling through the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway plays a prominent role in tumor immunity.”
From Hallmarks of response, resistance, and toxicity to immune checkpoint blockade (2021) · cites this paper as Gao et al., 2016
In the citing paper
“Defects associated with this pathway and its downstream effectors have shown both negative and positive correlations with response to ICB, suggesting a dual role for this pathway in tumor immunity (Ayers et al., 2017; Gao et al., 2016).”
From Hallmarks of response, resistance, and toxicity to immune checkpoint blockade (2021) · cites this paper as Gao et al., 2016
In the citing paper
“Loss of IFN-ɤ signaling could induce resistance to anti-CTLA-4 treatment (95).”
From Gut Microbiome as a Potential Factor for Modulating Resistance to Cancer Immunotherapy (2020) · cites this paper as [95]
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Citations
Cites
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607
New Guidelines to Evaluate the Response to Treatment in Solid Tumors
Therasse, P., Arbuck, S. G., Eisenhauer, E. A., Wanders, J., Kaplan, R. S., Rubinstein, L., Verweij, J., Van Glabbeke, M., van Oosterom, A. T., Christian, M. C., et al. (2000) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/92.3.205 · Cited by 15,660
Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
Wanchoo, R., Karam, S., Uppal, N. N., Barta, V. S., Deray, G., Devoe, C., Launay‐Vacher, V., Jhaveri, K. D., & on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors (2017) · American Journal of Nephrology · doi:10.1159/000455014 · Cited by 15,320
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
ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data
Wang, K., Li, M., & Hakonarson, H. H. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq603 · Cited by 14,724
Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer
Borghaei, H., Paz-Ares, L., Horn, L., Spigel, D. R., Steins, M., Ready, N. E., Chow, L. Q., Vokes, E. E., Felip, E., Holgado, E., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1507643 · Cited by 9,335
dbSNP: the NCBI database of genetic variation
Sherry, S. T. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.1.308 · Cited by 7,502
Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma
Motzer, R. J., Escudier, B., McDermott, D. F., George, S., Hammers, H. J., Srinivas, S., Tykodi, S. S., Sosman, J. A., Procopio, G., Plimack, E. R., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1510665 · Cited by 5,807
Self-citationaffy—analysis of Affymetrix GeneChip data at the probe level
Gautier, L., Cope, L., Bolstad, B. M., & Irizarry, R. A. (2004) · Bioinformatics · doi:10.1093/bioinformatics/btg405 · Cited by 5,221
Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples
Cibulskis, K., Lawrence, M. S., Carter, S. L., Sivachenko, A., Jaffe, D. B., Sougnez, C. L., Gabriel, S., Meyerson, M. M., Lander, E. S., & Getz, G. A. (2013) · Nature Biotechnology · doi:10.1038/nbt.2514 · Cited by 4,965
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Boulch, M., Cazaux, M., Cuffel, A., Guérin, M. V., Garcia, Z., Alonso, R., Lemaı̂tre, F., Beer, A., Corre, B., Menger, L., et al. (2023) · Nature Cancer · doi:10.1038/s43018-023-00570-7 · Cited by 143
Localization, tissue biology and T cell state — implications for cancer immunotherapy
Schenkel, J. M., & Pauken, K. E. (2023) · Nature reviews. Immunology · doi:10.1038/s41577-023-00884-8 · Cited by 144
“Moreover, tumour cells can halt T cell trafficking by inhibiting inflammatory pathways (such as type I and type II interferon (IFN) signalling) that drive chemokine production 86–88 .”
BackgroundInterpretable systems biomarkers predict response to immune-checkpoint inhibitors
Lapuente-Santana, Ó., van Genderen, M. N. G., Hilbers, P. A. J., Finotello, F., & Eduati, F. (2021) · Patterns · doi:10.1016/j.patter.2021.100293 · Cited by 142
Gamma delta T-cell-based immune checkpoint therapy: attractive candidate for antitumor treatment
Gao, Z., Bai, Y., Lin, A., Jiang, A., Zhou, C., Cheng, Q., Liu, Z., Chen, X., Zhang, J., & Luo, P. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01722-0 · Cited by 138
Xiang, Y., Liu, X., Wang, Y., Zheng, D., Meng, Q., Jiang, L., Yang, S., Zhang, S., Zhang, X., Liu, Y., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1366260 · Cited by 152
Evolution of delayed resistance to immunotherapy in a melanoma responder
Liu, D., Lin, J., Robitschek, E. J., Kasumova, G. G., Heyde, A., Shi, A., Kraya, A., Zhang, G., Moll, T. O. C., Frederick, D. T., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01331-8 · Cited by 139
“Tumor population was defined as GMM clusters 3,4,6,9,11 and the immune population was GMM cluster 1 (from Fig.”
Immune checkpoint blockade therapy
Wieder, T., Eigentler, T., Brenner, E., & Röcken, M. (2018) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2018.02.042 · Cited by 134
Immunoepigenetics Combination Therapies: An Overview of the Role of HDACs in Cancer Immunotherapy
Banik, D., Moufarrij, S., & Villagra, A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20092241 · Cited by 137
Molecular subtypes and precision treatment of triple-negative breast cancer
Zhao, S., Zuo, W., Shao, Z., & Jiang, Y. (2020) · Annals of Translational Medicine · doi:10.21037/atm.2020.03.194 · Cited by 140
“Besides PD-L1 expression, many other biomarkers have been suggested to predict tumor response to ICIs including TILs, tumor mutation burden and several single-gene biomarkers, such as EGFR amplification and IFN-γ expression (55,124-128).”
BackgroundFibrinogen-like protein 1 (FGL1): the next immune checkpoint target
Qian, W., Zhao, M., Wang, R., & Li, H. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01161-8 · Cited by 139
Acquired resistance in cancer: towards targeted therapeutic strategies
Soragni, A., Knudsen, E. S., O’Connor, T. N., Tognon, C. E., Tyner, J. W., Gini, B., Kim, D., Bivona, T. G., Zang, X., Witkiewicz, A. K., et al. (2025) · Nature reviews. Cancer · doi:10.1038/s41568-025-00824-9 · Cited by 151
“…in multiple IFNγ pathway genes, such as those encoding Janus kinase 1 (JAK1) and JAK2, and amplification of genes encoding suppressors of IFNγ signalling, lead to IFNγ insensitivity and T cell escape, conferring resistance to the blockade of PD1, PDL1 or CTLA4 in multiple cancer types 81,85,86 .”
Kalbasi, A. K., Tariveranmoshabad, M., Hakimi, K. N., Kremer, S. V., Campbell, K. M., Funes, J. M., Vega-Crespo, A., Parisi, G., Champhekar, A. S., Nguyen, C., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.abb0152 · Cited by 136
Abbas, H. A., Hao, D., Tomczak, K. J., Barrodia, P., Im, J. S., Reville, P. K., Alaniz, Z., Wang, W., Wang, R., Wang, F., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26282-z · Cited by 130
Self-citationMechanisms of Resistance to Immune Checkpoint Blockade
Liu, D., Jenkins, R. W., & Sullivan, R. J. (2018) · American Journal of Clinical Dermatology · doi:10.1007/s40257-018-0389-y · Cited by 135
Trial Watch: Immunomodulatory monoclonal antibodies for oncological indications
Buqué, A., Bloy, N., Aranda, F., Castoldi, F., Eggermont, A. M. M., Cremer, I., Fridman, W. H., Fucikova, J. P., Galon, J., Marabelle, A., et al. (2015) · OncoImmunology · doi:10.1080/2162402x.2015.1008814 · Cited by 132
Engineering interferons and interleukins for cancer immunotherapy
Holder, P. G., Lim, S. A., Huang, C., Sharma, P. A., Dagdas, Y. S., Bulutoglu, B., & Sockolosky, J. T. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114112 · Cited by 130
Self-citationBarriga, F. M., Tsanov, K. M., Ho, Y.-J., Sohail, N., Zhang, A., Baslan, T., Wuest, A. N., Del Priore, I., Meškauskaitė, B., Livshits, G., et al. (2022) · Nature Cancer · doi:10.1038/s43018-022-00443-5 · Cited by 125
Recent updates on cancer immunotherapy
Liu, M., & Guo, F. (2018) · Precision Clinical Medicine · doi:10.1093/pcmedi/pby011 · Cited by 133
IFN-γ-induced ER stress impairs autophagy and triggers apoptosis in lung cancer cells
Fang, C., Weng, T., Hu, S., Yuan, Z., Xiong, H., Huang, B. Y., Cai, Y., Li, L., & Fu, X. (2021) · OncoImmunology · doi:10.1080/2162402x.2021.1962591 · Cited by 129
“Loss of IFN-γ pathway genes in tumor cells reduces the chance of response to the immunotherapy with anti-CTLA-4.(3) New studies using state-of-the-art technology have shown that while IFN-γ secretion requires local antigen recognition, IFN-γ diffuses extensively to alter the”
BackgroundThe Cancer Immunogram as a Framework for Personalized Immunotherapy in Urothelial Cancer
van Dijk, N., Funt, S. A., Blank, C. U., Powles, T. B., Rosenberg, J. E., & van der Heijden, M. S. (2018) · European Urology · doi:10.1016/j.eururo.2018.09.022 · Cited by 121
de Andrade, L. F., Kumar, S., Luoma, A., Ito, Y., da Silva, P. H. A., Pan, D., Pyrdol, J. W., Yoon, C. H., & Wucherpfennig, K. W. (2020) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-19-0483 · Cited by 131
Reversal of pre-existing NGFR-driven tumor and immune therapy resistance
Boshuizen, J., Vredevoogd, D. W., Krijgsman, O., Ligtenberg, M. A., Blankenstein, S. A., de Bruijn, B., Frederick, D. T., Kenski, J. C. N., Parren, M., Brüggemann, M., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17739-8 · Cited by 122
Cancer Resistance to Immunotherapy: Comprehensive Insights with Future Perspectives
Said, S. S., & Ibrahim, W. N. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15041143 · Cited by 134
“Disturbances in the signaling pathways involved in antigen presentation can contribute to immune evasion by increasing the expression of PD-L1 or the secretion of chemokines that encourage the recruitment of immunosuppressive lymphocytes [33].”
BackgroundChromosomal instability as a driver of cancer progression
Chen, X., Agustinus, A. S., Li, J., Bona, M. D., & Bakhoum, S. F. W. (2024) · Nature Reviews Genetics · doi:10.1038/s41576-024-00761-7 · Cited by 146
“This result has been replicated using in vivo tumour models 162 , where depletion of the IFN gene cluster was shown to promote immunotherapy resistance to anti-CTLA4 treatment in B16 melanoma 163 .”
Mpakali, A., & Stratikos, E. (2021) · Cancers · doi:10.3390/cancers13010134 · Cited by 130
“Multiple studies have linked defects in IFNγ signaling with resistance to ICI therapy [16,17,102,103].”
BackgroundDUX4 Suppresses MHC Class I to Promote Cancer Immune Evasion and Resistance to Checkpoint Blockade
Chew, G.-L., Campbell, A. E., Neef, E. D., Sutliff, N. A., Shadle, S. C., Tapscott, S. J., & Bradley, R. K. (2019) · Developmental Cell · doi:10.1016/j.devcel.2019.06.011 · Cited by 132
mTORC1 upregulates B7-H3/CD276 to inhibit antitumor T cells and drive tumor immune evasion
Liu, H.-J., Du, H., Khabibullin, D., Zarei, M., Wei, K., Freeman, G. J., Kwiatkowski, D. J., & Henske, E. P. (2023) · Nature Communications · doi:10.1038/s41467-023-36881-7 · Cited by 125
Significance of Tumor Mutation Burden in Immune Infiltration and Prognosis in Cutaneous Melanoma
Kang, K., Xie, F., Mao, J., Bai, Y., & Wang, X. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.573141 · Cited by 127
“Although PD-L1 immunohistochemistry is the most widely used test to estimate the treatment response to ICIs, it has no influence on the treatment decision in most cases (14, 15).”
BackgroundInfluentialMultimodel preclinical platform predicts clinical response of melanoma to immunotherapy
Pérez‐Guijarro, E., Yang, H. H., Araya, R. E., Meskini, R. E., Michael, H. T., Vodnala, S. K., Marie, K. L., Smith, C., Chin, S., Lam, K. C., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0818-3 · Cited by 119
Immune-checkpoint inhibitor resistance in cancer treatment: Current progress and future directions
Zhang, C., Zhang, C., & Wang, H. (2023) · Cancer Letters · doi:10.1016/j.canlet.2023.216182 · Cited by 125
Recent advances in the clinical development of immune checkpoint blockade therapy
Ghahremanloo, A., Soltani, A., Modaresi, S. M. S., & Hashemy, S. I. (2019) · Cellular Oncology · doi:10.1007/s13402-019-00456-w · Cited by 119
Predictive biomarkers for response to immune checkpoint inhibition
Shum, B., Larkin, J., & Turajlic, S. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.03.036 · Cited by 118
IFN-γ-dependent NK cell activation is essential to metastasis suppression by engineered Salmonella
Lin, Q., Li, R., Jia, X., Li, R., Yu, B., Hu, J., Luo, X., Badea, S. R., Chen, X., Fu, G., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22755-3 · Cited by 118
A local human Vδ1 T cell population is associated with survival in nonsmall-cell lung cancer
Wu, Y., Biswas, D., Usaite, I., Angelova, M., Boeing, S., Karasaki, T., Veeriah, S., Czyzewska-Khan, J., Morton, C., Joseph, M., et al. (2022) · Nature Cancer · doi:10.1038/s43018-022-00376-z · Cited by 126
Gut Microbiome as a Potential Factor for Modulating Resistance to Cancer Immunotherapy
Shui, L., Yang, X., Li, J., Yi, C., Sun, Q., & Zhu, H. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02989 · Cited by 115
“Loss of IFN-È signaling could induce resistance to anti-CTLA-4 treatment (95).”
BackgroundFBXO44 promotes DNA replication-coupled repetitive element silencing in cancer cells
Shen, J. Z., Qiu, Z., Wu, Q., Finlay, D., Garcia, G., Sun, D., Rantala, J., Barshop, W., Hope, J. L., Gimple, R. C., et al. (2021) · Cell · doi:10.1016/j.cell.2020.11.042 · Cited by 113
Brown, Z. J., Yu, S. J., Heinrich, B., Ma, C., Fu, Q., Sandhu, M., Agdashian, D., Zhang, Q., Korangy, F., & Greten, T. F. (2018) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-018-2190-4 · Cited by 119
SOX17 enables immune evasion of early colorectal adenomas and cancers
Goto, N., Westcott, P. M. K., Goto, S., Imada, S., Taylor, M. S., Eng, G. M., Braverman, J., Deshpande, V., Jacks, T., Agudo, J., et al. (2024) · Nature · doi:10.1038/s41586-024-07135-3 · Cited by 119
Bai, X., Fisher, D. E., & Flaherty, K. T. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0204-6 · Cited by 107
Preexisting Autoimmune Disease: Implications for Immune Checkpoint Inhibitor Therapy in Solid Tumors
Kennedy, L. C., Bhatia, S., Thompson, J. A., & Grivas, P. D. (2019) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2019.7310 · Cited by 117
ERS/ESTS/EACTS/ESTRO guidelines for the management of malignant pleural mesothelioma
Opitz, I., Scherpereel, A., Berghmans, T., Psallidas, I., Glatzer, M., Comas, D. R., Astoul, P. J., Bölükbas, S., Boyd, J., Coolen, J., et al. (2020) · European Journal of Cardio-Thoracic Surgery · doi:10.1093/ejcts/ezaa158 · Cited by 114
Fan, Z., Wu, C., Chen, M., Jiang, Y., Wu, Y., Mao, R., & Fan, Y. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.09.010 · Cited by 120
Noncoding RNA s and immune checkpoints—clinical implications as cancer therapeutics
Smolle, M. A., Calin, H. N., Pichler, M., & Călin, G. A. (2017) · FEBS Journal · doi:10.1111/febs.14030 · Cited by 114
Zhang, J., Zhou, N., Lin, A., Luo, P., Chen, X., Deng, H., Kang, S., Guo, L., Zhu, W., & Zhang, J. (2020) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-020-02668-8 · Cited by 110
“) [28, 29], interferon signal pathway gene mutations [30, 31], driver gene mutations (KRAS, BRAF, ALK, EGFR, etc.”
BackgroundLiu, Z., Liu, W., Wang, W., Ma, Y., Wang, Y., Drum, D. L., Cai, J., Blevins, H., Lee, E., Shah, S., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2302878120 · Cited by 121
Lepletier, A., Madore, J., O’Donnell, J. S., Johnston, R. L., Li, X.-Y., McDonald, E., Ahern, E. S., Kuchel, A., Eastgate, M. A., Pearson, S., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-3925 · Cited by 110
Qiu, J., Xu, B., Ye, D., Ren, D., Wang, S., Benci, J. L., Xu, Y., Ishwaran, H., Beltra, J., Wherry, E. J., et al. (2023) · Nature Cancer · doi:10.1038/s43018-022-00490-y · Cited by 117
Escape from IFN-γ-dependent immunosurveillance in tumorigenesis
Lin, C., Lin, C.-M., Lee, K.-Y., Chen, K.-Y., Feng, P., Chen, C., Chuang, H., Chen, C.-L., Wang, Y., Tseng, P., et al. (2017) · Journal of Biomedical Science · doi:10.1186/s12929-017-0317-0 · Cited by 112
Kong, Y., Xu, C., Cui, C., Yang, W., Yang, S., Chi, Z., Sheng, X., Si, L., Xie, Y., Yu, R., et al. (2021) · npj Genomic Medicine · doi:10.1038/s41525-021-00169-w · Cited by 119
Zhong, Z., Vong, C. T., Chen, F., Tan, H., Zhang, C., Wang, N., Cui, L., Wang, Y., & Feng, Y. (2022) · Medicinal Research Reviews · doi:10.1002/med.21876 · Cited by 113
Mechanisms of Tumor Cell–Intrinsic Immune Evasion
Spranger, S., & Gajewski, T. F. (2017) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-030617-050606 · Cited by 113
Cancer cell-intrinsic mechanisms driving acquired immune tolerance
Ghorani, E., Swanton, C., & Quezada, S. A. (2023) · Immunity · doi:10.1016/j.immuni.2023.09.004 · Cited by 116
“179,180 Cancer cells can harbor defects in IFN-g signaling pathway components, 181,182 particularly associated with immunotherapy resistance 183,184 — although in some settings, loss of IFN-g signaling can sensitize cancer cells to immune control.”
BackgroundDobosz, P., Stępień, M., Golke, A., & Dzieciątkowski, T. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052847 · Cited by 114
Zhou, X., Ni, Y., Liang, X., Lin, Y., An, B., He, X., & Zhao, X. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.915094 · Cited by 111
The immune response‐related mutational signatures and driver genes in non‐small‐cell lung cancer
Chen, H., Chong, W., Teng, C., Yao, Y., Wang, X., & Li, X. (2019) · Cancer Science · doi:10.1111/cas.14113 · Cited by 106
Nishida, M., Yamashita, N., Ogawa, T., Koseki, K., Warabi, E., Ohue, T., Komatsu, M., Matsushita, H., Kakimi, K., Kawakami, E., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-002954 · Cited by 109
CARM1 Inhibition Enables Immunotherapy of Resistant Tumors by Dual Action on Tumor Cells and T Cells
Kumar, S., Zeng, Z., Bagati, A., Tay, R. E., Sanz, L. A., Hartono, S. R., Ito, Y., Abderazzaq, F. O., Hatchi, E., Jiang, P., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1144 · Cited by 106
“Poor infiltration by CD8 T cells is associated with an absence of a type 1 interferon gene expression signature (23, 24).”
BackgroundHuang, L., Malu, S., McKenzie, J. A., Andrews, M. C., Talukder, A. H., Tieu, T., Karpinets, T., Haymaker, C., Forget, M.-A., Williams, L. J., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-2483 · Cited by 102
Self-citationCancer vaccines: current status and future directions
Zhou, Y., Wei, Y., Tian, X., & Wei, X. (2025) · Journal of Hematology & Oncology · doi:10.1186/s13045-025-01670-w · Cited by 121
“Examples include IFN signaling mutation, WNT/β-catenin activation, and the loss of phosphatase and ten-sin homolog [262–265].”
Drug resistance in cancer: molecular mechanisms and emerging treatment strategies
Li, J., Hu, J., Yang, Y., Zhang, H., Liu, Y., Fang, Y., Qu, L., Lin, A., Luo, P., Jiang, A., et al. (2025) · Molecular Biomedicine · doi:10.1186/s43556-025-00352-w · Cited by 120
Pech, M. F., Fong, L. E., Villalta, J. E., Chan, L. J., Kharbanda, S., O’Brien, J. J., McAllister, F. E., Firestone, A. J., Jan, C. H., & Settleman, J. E. (2019) · eLife · doi:10.7554/elife.47362 · Cited by 98
Inhibition of PI3K pathway increases immune infiltrate in muscle-invasive bladder cancer
Borcoman, É., Rochère, P. D. L., Richer, W., Vacher, S., Chemlali, W., Krucker, C., Sirab, N., Radvanyi, F., Allory, Y., Pignot, G., et al. (2019) · OncoImmunology · doi:10.1080/2162402x.2019.1581556 · Cited by 96
“FOXP3 to identify Tregs, see Table 1 for the complete list), ii) a selection of immunomodulatory genes comprising druggable immune checkpoints (in clinical use or under evaluation) and including at least one member of the most studied families,(18) and iii) major histocompatibility complex (MHC) genes (HLA genes) and…”
MethodSabaawy, H. E., Ryan, B. M., Khiabanian, H., & Pine, S. R. (2021) · Carcinogenesis · doi:10.1093/carcin/bgab075 · Cited by 106
The CD58-CD2 axis is co-regulated with PD-L1 via CMTM6 and shapes anti-tumor immunity
Ho, P., Melms, J. C., Rogava, M., Frangieh, C. J., Poźniak, J., Shah, S. B., Walsh, Z. H., Kyrysyuk, O., Amin, A. D., Caprio, L., et al. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.05.014 · Cited by 103
Self-citationSong, K., Oh, S. J., Kim, S., Cho, H., Lee, H.-J., Song, J. S., Chung, J., Cho, E., Lee, J., Jeon, S., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-14259-y · Cited by 96
Understanding CAR T cell-tumor interactions: Paving the way for successful clinical outcomes
Korell, F., Berger, T. R., & Maus, M. V. (2022) · Med · doi:10.1016/j.medj.2022.05.001 · Cited by 103
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 101
Kobayashi, Y., Lim, S., & Yamaguchi, H. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.11.011 · Cited by 96
The Multifaceted Role of Th1, Th9, and Th17 Cells in Immune Checkpoint Inhibition Therapy
Lee, J., Lozano‐Ruiz, B., Yang, F. M., Fan, D. D., Shen, L., & González-Navajas, J. M. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.625667 · Cited by 102
“In fact, a surprisingly high proportion (9 out of 12) of metastatic melanoma patients that do not respond to Ipilimumab harbor tumors with loss of IFN-g signaling (48).”
BackgroundAlemohammad, H., Najafzadeh, B., Asadzadeh, Z., Baghbanzadeh, A., Ghorbaninezhad, F., Najafzadeh, A., Safarpour, H., Bernardini, R., Brunetti, O., Sonnessa, M., et al. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112516 · Cited by 92
Mutational and Antigenic Landscape in Tumor Progression and Cancer Immunotherapy
Vitale, I., Sistigu, A., Manic, G., Rudqvist, N.-P., Trajanoski, Z., & Galluzzi, L. (2019) · Trends in Cell Biology · doi:10.1016/j.tcb.2019.01.003 · Cited by 95
Onuma, A. E., Zhang, H., Huang, H., Williams, T. M., Noonan, A. M., & Tsung, A. (2020) · Gene Expression · doi:10.3727/105221620x15880179864121 · Cited by 95
Bifidobacterium Strain-Specific Enhances the Efficacy of Cancer Therapeutics in Tumor-Bearing Mice
Yoon, Y., Kim, G., Jeon, B., Fang, S., & Park, H. (2021) · Cancers · doi:10.3390/cancers13050957 · Cited by 91
“Mutations in IFN-γ signaling genes were identified in tumors resistant to cancer immunotherapy, highlighting the essential role for this protein in chemotherapy responses [68,69].”
BackgroundRegulatory mechanisms of PD-L1 expression in cancer cells
Shi, Y. (2018) · Cancer Immunology, Immunotherapy · doi:10.1007/s00262-018-2226-9 · Cited by 92
Melanoma response to anti-PD-L1 immunotherapy requires JAK1 signaling, but not JAK2
Luo, N., Formisano, L., Ericsson, P. I. G., Sanchez, V. M., Dean, P. T., Opalenik, S. R., Sanders, M. E., Cook, R. S., Arteaga, C. L., Johnson, D. B., et al. (2018) · OncoImmunology · doi:10.1080/2162402x.2018.1438106 · Cited by 94
Beane, J., Mazzilli, S. A., Campbell, J. D., Duclos, G. E., Krysan, K., Moy, C. H., Perdomo, C., Schäffer, M., Liu, G., Zhang, S., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09834-2 · Cited by 95
“Disruptions in proper T cell mediated immunosurveillence have been described in several studies showing that impaired HLA class I antigen processing and presentation including down-regulation or loss of B2M(37, 38) and interferon signaling(39) in lung tumors affects response and acquired resistance to checkpoint inhib…”
BackgroundNew pathways in immune stimulation: targeting OX40
Silva, C. A. C., Facchinetti, F., Routy, B., & Derosa, L. (2020) · ESMO Open · doi:10.1136/esmoopen-2019-000573 · Cited by 94
Walsh, R. J., & Soo, R. A. (2020) · Therapeutic Advances in Medical Oncology · doi:10.1177/1758835920937902 · Cited by 93
The perfect personalized cancer therapy: cancer vaccines against neoantigens
Aurisicchio, L., Pallocca, M., Ciliberto, G., & Palombo, F. (2018) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-018-0751-1 · Cited by 93
FOXA1 overexpression suppresses interferon signaling and immune response in cancer
He, Y., Wang, L., Wei, T., Xiao, Y., Sheng, H., Su, H., Hollern, D. P., Zhang, X., Ma, J., Wen, S., et al. (2021) · Journal of Clinical Investigation · doi:10.1172/jci147025 · Cited by 96
“lymphocyte (CTL)-mediated killing of cancer cells (7-12).”
BackgroundInfluentialMechanisms of Intrinsic Tumor Resistance to Immunotherapy
Rieth, J. M., & Subramanian, S. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19051340 · Cited by 92
Toward a comprehensive view of cancer immune responsiveness: a synopsis from the SITC workshop
Society for Immunotherapy of Cancer (SITC) Cancer Immune Responsiveness Task Force and Working Groups, Bedognetti, D., Ceccarelli, M., Galluzzi, L., Lu, R. O., Palucka, K., Samayoa, J. A., Spranger, S., Warren, S. E., Wong, K., et al. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0602-4 · Cited by 90
IRF1 Inhibits Antitumor Immunity through the Upregulation of PD-L1 in the Tumor Cell
Shao, L., Hou, W., Scharping, N. E., Vendetti, F. P., Srivastava, R., Roy, C. N., Menk, A. V., Wang, Y., Chauvin, J.-M., Karukonda, P., et al. (2019) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-18-0711 · Cited by 90
Marchini, A., Daeffler, L., Pozdeev, V. I., Angelova, A. L., & Rommelaere, J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01848 · Cited by 95
“In addition treatment resistance is common (54, 55) influenced at least in part by patient HLA class I genotype (56).”
BackgroundWood, M. A., Weeder, B. R., David, J. K., Nellore, A., & Thompson, R. F. (2020) · Genome Medicine · doi:10.1186/s13073-020-00729-2 · Cited by 94
“Availability of data and materials Data used in these analyses is available on the Sequence Read Archive under accessions PRJNA278450 [4], PRJNA293912 [3], PRJNA305077 [68], PRJNA306070 [6], PRJNA307199 [5], PRJNA312948 [5], PRJNA324705 [12], PRJNA343789 [5], PRJNA357321 [13], PRJNA369259 [14], PRJNA414014 [16], PRJNA…”
MethodBase editing screens map mutations affecting interferon-γ signaling in cancer
Coelho, M. A., Cooper, S., Strauß, M. E., Karakoç, E., Bhosle, S. G., Gonçalves, E., Picco, G., Burgold, T., Cattaneo, C. M., Veninga, V., et al. (2023) · Cancer Cell · doi:10.1016/j.ccell.2022.12.009 · Cited by 94
Huang, X., Hu, M., Sun, T., Li, J., Zhou, Y., Yan, Y., Xuan, B., Wang, J., Xiong, H., Ji, L., et al. (2023) · Cell Host & Microbe · doi:10.1016/j.chom.2023.10.005 · Cited by 94
The Resistance Mechanisms of Lung Cancer Immunotherapy
Wang, F., Wang, S., & Zhou, Q. H. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.568059 · Cited by 90
Immunotherapy resistance in non-small-cell lung cancer: From mechanism to clinical strategies
Zhou, S., & Yang, H. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1129465 · Cited by 98
Activated SUMOylation restricts MHC class I antigen presentation to confer immune evasion in cancer
Demel, U. M., Böger, M., Yousefian, S., Grunert, C., Zhang, L., Hotz, P. W., Gottschlich, A., Köse, H., Isaakidis, K., Vonficht, D., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci152383 · Cited by 88
Marijt, K. A., Sluijter, M., Blijleven, L., Tolmeijer, S. H., Scheeren, F. A., van der Burg, S. H., & van Hall, T. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0627-8 · Cited by 85
Tumor CDKN2A-Associated JAK2 Loss and Susceptibility to Immunotherapy Resistance
Horn, S., Leonardelli, S., Sucker, A., Schadendorf, D., Griewank, K., & Paschen, A. (2017) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djx271 · Cited by 86
Bridge, J. A., Lee, J., DAUD, A. I., Wells, J. W., & Bluestone, J. A. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00351 · Cited by 86
Efficient identification of neoantigen-specific T-cell responses in advanced human ovarian cancer
Liu, S., Matsuzaki, J., Wei, L., Tsuji, T., Battaglia, S., Hu, Q., Cortes, E., Wong, L.-P., Yan, L., Long, M. D., et al. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0629-6 · Cited by 85
Vijayakumar, G., McCroskery, S., & Palese, P. (2019) · Journal of Virology · doi:10.1128/jvi.01677-19 · Cited by 83
Immune Therapy Resistance and Immune Escape of Tumors
Seliger, B., & Massa, C. (2021) · Cancers · doi:10.3390/cancers13030551 · Cited by 84
Nguyen, T.-T., Ramsay, L., Ahanfeshar-Adams, M., Lajoie, M., Schadendorf, D., Alain, T., & Watson, I. R. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-3365 · Cited by 87
Targeting Cytokine Therapy to the Pancreatic Tumor Microenvironment Using PD-L1–Specific VHHs
Dougan, M. L., Ingram, J. R., Jeong, H., Mosaheb, M. M., Bruck, P. T., Ali, L. R., Pishesha, N., Blomberg, O. S., Tyler, P. M., Servos, M. M., et al. (2018) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-17-0495 · Cited by 85
Guadecitabine Plus Ipilimumab in Unresectable Melanoma: The NIBIT-M4 Clinical Trial
Giacomo, A. M. D., Covre, A., Finotello, F., Rieder, D., Danielli, R., Sigalotti, L., Giannarelli, D., Petitprez, F., Lacroix, L., Valente, M., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-1335 · Cited by 83
FOXD3 Regulates VISTA Expression in Melanoma
Rosenbaum, S. R., Knecht, M., Mollaee, M., Zhong, Z., Erkes, D. A., McCue, P. A., Chervoneva, I., Berger, A. C., Lo, J. A., Fisher, D. E., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2019.12.036 · Cited by 85
“Furthermore, since VISTA and PD-L1 are differentially regulated by IFNg, VISTA expression or targeting is unlikely to be affected by defects in IFNg signaling associated with resistance to immune checkpoint blockade (Gao et al., 2016).”
Background
Metadata
- Authors
- Gao, J., Shi, L. Z., Zhao, H., Chen, J., Xiong, L., He, Q., Chen, T., Roszik, J., Bernatchez, C., Woodman, S. E., Chen, P.-L., Hwu, P., Allison, J. P., Futreal, A., Wargo, J. A., & Sharma, P.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Sharma, Padmanee
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-10
- Volume
- 167
- Issue
- 2
- Pages
- 397-404.e9
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5088716
- OpenAlex
- W2522313999
- Cited by
- 1,300
- References
- 41
- Citations by year
- 2026: 83 · 2025: 107 · 2024: 128 · 2023: 158 · 2022: 137 · 2021: 174 · 2020: 162 · 2019: 128 · 2018: 121 · 2017: 89 · 2016: 8
- FWCI
- 62.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (L30 CA117817, R01CA163793, K08CA160692, P30CA016672, K12CA088084)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- interferon-gamma signaling, IFNGR1, CTLA-4 blockade, ipilimumab, metastatic melanoma, immune checkpoint therapy, tumor rejection, prognostic factors, T cell response
- MeSH terms
- Ipilimumab, Interferon gamma Receptor, Animals, Antibodies, Monoclonal, Humans, Interferon-gamma, Melanoma, Melanoma, Experimental, Mice, Inbred C57BL, Skin Neoplasms, T-Lymphocytes, Cytokines, Receptors, Interferon, Drug Resistance, Neoplasm, Cell Line, Tumor, Mice, Gene Knockdown Techniques, CTLA-4 Antigen
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