The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
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.
Overview
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
Cites
Statistics
Verification
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?
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
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
Flagged first, then by citations
Cited by
Sorted by citations
Items 901–1,000 of 1,000
Kim, Y., Kim, K., Lee, K. H., Kim, J., & Jung, W. (2020) · Scientific Reports · doi:10.1038/s41598-020-69082-z · Cited by 9
Leal, J. L., & John, T. (2022) · Clinical Lung Cancer · doi:10.1016/j.cllc.2022.08.009 · Cited by 9
The soldiers needed to be awakened: Tumor-infiltrating immune cells
Yaping, W., Wang, Z., Zhuling, C., Li, R., Pengyu, F., Lili, G., Cheng, J., Bo, Z., Liu, L., Guangdong, H., et al. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.988703 · Cited by 9
Xie, Y., Zhang, W., Sun, J. M., Sun, L., Meng, F., & Yu, H. (2022) · Scientific Reports · doi:10.1038/s41598-022-22962-y · Cited by 9
Hargadon, K. M., Győrffy, B., & McGee, T. J. (2020) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2021.1847644 · Cited by 9
Hogg, S. J., Motorna, O., Kearney, C. J., Derrick, E. B., House, I. G., Todorovski, I., Kelly, M. J., Zethoven, M., Bromberg, K. D., Lai, A., et al. (2022) · Clinical Epigenetics · doi:10.1186/s13148-022-01316-5 · Cited by 8
“In contrast, genetic aberrations that suppress IFNγ signaling are detected in patients relapsing from immune checkpoint blockade demonstrating that tumor-intrinsic IFNγ signaling is a clinically relevant mechanism of immune evasion [5].”
BackgroundTherapeutic Advances in Advanced Basal Cell Carcinoma
Alkassis, S., Shatta, M., & Wong, D. J. L. (2024) · Cancers · doi:10.3390/cancers16173075 · Cited by 10
“Upregulation of HLA class I expression by Interferon gamma (IFN γ ) released by tumor-infiltrating T cell [68] and alterations in IFN γ signaling pathways have been identified as mechanisms of resistance in other histologies [69,70].”
BackgroundLiao, Y., Yang, R., Wang, B., Ruan, Y., Cui, L., Yang, J., Yu, X., Han, S., Yao, Y., Luan, X., et al. (2024) · Oncogene · doi:10.1038/s41388-024-03255-2 · Cited by 8
A comprehensive insights of cancer immunotherapy resistance
Das, L., & Das, S. (2025) · Medical Oncology · doi:10.1007/s12032-025-02605-8 · Cited by 9
“Several genetic analyses revealed, that immunotherapy non-responder patients have a higher frequency of mutation in the IFNγ pathway genes such as IFNγ receptor 1 and 2 (IFNGR1/2), JAK2, and interferon regulatory factor 1 (IRF1) [99].”
Tiedje, V., Greenberg, J., Qin, T., Im, S.-Y., Krishnamoorthy, G. P., Boucai, L., Xu, B., French, J. D., Sherman, E. J., Ho, A. L., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci191781 · Cited by 9
van Dam, S., Krijgsman, D., Küçükköse, E., Verdonschot, M. E. L., Amini, M., Blokx, W. A. M., van Eijs, M. J. M., Verheijden, R. J., Kranenburg, O., Suijkerbuijk, K. P. M., et al. (2025) · British Journal of Cancer · doi:10.1038/s41416-025-03137-8 · Cited by 9
van der Geest, D., Vliet, A. V., Peeper, D. S., Haanen, J. B. A. G., Smit, E. F., & Theelen, W. S. M. E. (2025) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2025-013110 · Cited by 9
“93 This was recently argued by Song and Chow, who showed that tumor intrinsic mutations in IFN-γ signaling genes when present prior to treatment do sensitize a tumor to ICI treat-ment.”
MYC at the tumor–immune interface: mechanisms of immune escape and immunotherapy resistance
González-Larreategui, Í., Martin, M. C., Casacuberta‐Serra, S., & Soucek, L. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1738440 · Cited by 10
A comprehensive review of mechanisms underlying resistance to immune checkpoint inhibitors
Bertucci, A., -, D. T. K., Billon, E., Fernez, T., & Rochigneux, P. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1735741 · Cited by 11
Striking the right balance with type I interferon signalling in cancer
Chadwick, T. B., So, J., Hertzog, P. J., Haynes, N. M., & Parker, B. S. (2026) · Nature reviews. Cancer · doi:10.1038/s41568-026-00915-1 · Cited by 14
“Recombinant IFNα2b remains approved for melanoma, renal cell carcinoma and certain haematological malignancies, yet its use is largely historical 250,251 .”
Vredevoogd, D. W., Apriamashvili, G., & Peeper, D. S. (2021) · Immuno-Oncology Technology · doi:10.1016/j.iotech.2021.100043 · Cited by 7
“Aside from the intertumor heterogeneity in NK ligand expression that may determine whether IFN-g pathway mutant tumors are able to recruit and activate NK cells,(3,68-71) mutational analyses of patient tumors show a diverse range of mutations in downstream components of the IFN-g pathway that may (subtly) affect signa…”
BackgroundCediranib enhances the transcription of MHC-I by upregulating IRF-1
Zhang, J., Guo, H., Wang, L., Zheng, M., Kong, S., Wu, H., Zhao, L., Zhao, Q., Yang, X., He, Q., et al. (2024) · Biochemical Pharmacology · doi:10.1016/j.bcp.2024.116036 · Cited by 8
Self-citationYang, Y., Bo, S., Liang, L., Deng, K., Bai, L.-Y., Wang, T., Wang, Y.-S., Liu, K.-B., & Lu, C.-W. (2024) · ACS Nano · doi:10.1021/acsnano.3c10972 · Cited by 13
Future of Immune Checkpoint Inhibitors
Maawy, A. A., & Ito, F. (2018) · Elsevier eBooks · doi:10.1016/b978-0-323-54948-6.00012-3 · Cited by 8
The Era of Checkpoint Inhibition: Lessons Learned from Melanoma
Paschen, A., & Schadendorf, D. (2019) · Recent results in cancer research/Recent Results in Cancer Research · doi:10.1007/978-3-030-23765-3_6 · Cited by 9
Zhang, Q., Chen, Y., Bai, X., & Liang, T. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.590058 · Cited by 8
“Similarly, genetic alterations down-regulating the interferon signaling such as IFNGR1, IFNGR2, and IRF1, and amplification of genes that inhibit interferon-gamma such as SOCS1 and PIAS4 can weaken the efficacy of ICIs (33).”
BackgroundAPLNR Regulates IFN-γ signaling via β-arrestin 1 mediated JAK-STAT1 pathway in melanoma cells
Liu, Y., Ma, X., Yang, H., Li, X., Ma, Y., Ason, B., Liu, S., & Hu, L. A. (2022) · Biochemical Journal · doi:10.1042/bcj20210813 · Cited by 8
Hafstrand, I., Doorduijn, E. M., Sun, R., Talyzina, A. A., Sluijter, M., Pellegrino, S., Sandalova, T., Duru, A. D., van Hall, T., & Achour, A. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1700228 · Cited by 8
Lei, X., Zhao, G., Xie, Y., & Cui, N. (2024) · Mediators of Inflammation · doi:10.1155/2024/4233439 · Cited by 7
Omri, L., Naigeon, M., Flippot, R., Gavira, J., Poveda-Ferriols, J. M., Nguyen, D. J. M., Abdi, C., Arroyo-Salgado, A., Chaput, N., de Velasco, G., et al. (2024) · Exploration of Targeted Anti-tumor Therapy · doi:10.37349/etat.2024.00271 · Cited by 8
Gfi1 controls the formation of effector-like CD8+ T cells during chronic infection and cancer
Ojo, O. A., Shen, H., Ingram, J. T., Bonner, J. A., Welner, R. S., Lacaud, G., Zajac, A. J., & Shi, L. Z. (2025) · Nature Communications · doi:10.1038/s41467-025-59784-1 · Cited by 9
Self-citationPersistent IFN-γ signaling in acquired resistance to PD-(L)1 blockade in NSCLC
Karri, V., & Dalia, S. M. (2025) · Journal of Translational Genetics and Genomics · doi:10.20517/jtgg.2025.90 · Cited by 8
Mucosal Melanoma: Mechanisms of Its Etiology, Progression, Resistance and Therapy
Hassan, S.-Y., Flanagan, T. W., Hassan, S.-L., Facca, S., Haïkel, Y., & Hassan, M. (2025) · Cells · doi:10.3390/cells14231884 · Cited by 7
“While disruption of the IFN signaling pathway in melanoma negatively affects tumor response to anti-CTLA-4 therapy [255,256], extensive IFN-γ exposure of melanoma cells increased their resistance to radiotherapy and anti-CTLA-4 treatment [27,257].”
Stochasticity in cancer immunotherapy stems from rare but functionally critical Spark T cells
Salazar-Cavazos, E., Jia, D., Missolo-Koussou, Y., Kenet, A. L., Achar, S. R., Dada, H., Kondo, T., Krishnan, A. Y., Taylor, N. N., Klemen, N. D., et al. (2026) · Cell · doi:10.1016/j.cell.2025.12.026 · Cited by 8
Hu, M., Liu, D.-A., Wortzel, I., Collier, P., Nelson, T. M., Foox, J., Zhong, G., Tobias, G. C., Asao, T., Bojmar, L., et al. (2026) · Cancer Cell · doi:10.1016/j.ccell.2026.03.023 · Cited by 7
“15,16 20 Therefore, identifying alternative mechanisms to enhance tumor antigen presentation could lead to more effective anti-tumor immune responses.”
Targeting the immune microenvironment during immunotherapy for solid tumors
Sabaawy, A., & Zeeshan, S. (2021) · Molecular & Cellular Oncology · doi:10.1080/23723556.2021.1994327 · Cited by 7
Sauerer, T., Lischer, C., Weich, A., Berking, C., Vera, J., & Dörrie, J. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.785662 · Cited by 7
Sham, N. F. R., Hasani, N. A. H., Hasan, N., Karim, M. K. A., Fuad, S. B. S. A., Hasbullah, H. H., & Ibahim, M. J. (2023) · Scientific Reports · doi:10.1038/s41598-023-29925-x · Cited by 7
Overcoming melanoma resistance to immune checkpoint blockade therapy using nano-strategies
Ding, Y., Liu, C., Wu, Y., & Fu, F. (2023) · Biomedical Technology · doi:10.1016/j.bmt.2023.03.003 · Cited by 7
Zhang, L., Cao, L., Li, S., Wang, L., Song, Y., Huang, Y., Xu, Z., He, J., Wang, M., & Li, K. (2023) · Journal of Immunotherapy · doi:10.1097/cji.0000000000000475 · Cited by 7
“We also found that the results were closer using mutations or CNVs data alone, but the result was poorer without transfer-learning and pre-training, obtaining only AUROC of 0.486 (Supplementary Table S3, Supplemental Digital Content 6, http://links.lww. com/JIT/A753).”
BackgroundInfluentialMafosfamide Boosts GMI-HBVac against HBV via Treg Depletion in HBV-Infected Mice
Lin, Q., Zhong, Y., & Wang, B. (2023) · Vaccines · doi:10.3390/vaccines11061026 · Cited by 6
Unraveling the Complexities of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma
Han, X., Sun, Q., Xu, M., Zhu, G., Gao, R., Ni, B., & Li, J. (2023) · Seminars in Liver Disease · doi:10.1055/s-0043-1776127 · Cited by 7
Hazra, R., Chattopadhyay, S., Mallick, A., Gayen, S., & Roy, S. (2024) · Medical Oncology · doi:10.1007/s12032-024-02416-3 · Cited by 8
“The absence of IFN-gamma signaling has been associated with resistance to anti-CTLA-4 therapy [140].”
Wang, Y., Ding, L., Lin, Z., Li, B., Hu, D., Zhang, S., Zhou, S., Ning, Y., Xin, F., Ying, Y., et al. (2025) · Chemical Engineering Journal · doi:10.1016/j.cej.2025.160294 · Cited by 8
Guia, S., Fenis, A., de Chanville, C. B., Galluso, J., Khlifi, H. M., Escalière, B., Modelska, A., Vienne, M., Lopes, N., Pouchin, A., et al. (2025) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2024-010699 · Cited by 7
“46 Patients with melanoma who do not respond to anti- CTLA-4 (ipilimumab) 46 or those with metastatic melanoma experiencing relapses after anti-programmed cell death 1 (PD-1) therapy (pembrolizumab) 47 have tumors with genomic defects in IFN-γ pathway genes.”
Identification of DDX60 as a Regulator of MHC-I Class Molecules in Colorectal Cancer
Geng, N., Hu, T., & He, C. (2022) · Biomedicines · doi:10.3390/biomedicines10123092 · Cited by 7
Targeting Features of Curaxin CBL0137 on Hematological Malignancies In Vitro and In Vivo
Fetisov, T. I., Анатольевна, Б. А., Antipova, A. S., Antoshina, E. E., Trukhanova, L. S., Gorkova, T., Zuevskaya, S. N., Maslov, A. A., Gurova, K. V., Gudkov, A. V., et al. (2023) · Biomedicines · doi:10.3390/biomedicines11010230 · Cited by 7
“9 * * * IFNG The target gene that positively regulates the immune response [57] −4.”
BackgroundIvanović, T., Božić, D., Benzon, B., Čapkun, V., Vukojević, K., & Durdov, M. G. (2023) · Biomedicines · doi:10.3390/biomedicines11030709 · Cited by 7
“Contradictorily, in clinical practice, patients who do not respond to CTLA-4 immunotherapy are those with genomic defects of IFN-γ pathway genes [35].”
BackgroundA benzoxazole derivative PO‐296 inhibits T lymphocyte proliferation by the JAK3/STAT5 signal pathway
Luo, X., Zhou, H., Wang, S., Xiong, J., Mo, C., Guo, H., Wang, Y., Yang, S., Li, L., Zou, Q., et al. (2018) · Journal of Cellular Biochemistry · doi:10.1002/jcb.28195 · Cited by 7
neoepiscope improves neoepitope prediction with multi-variant phasingPreprint
Wood, M. A., Nguyen, A., Struck, A. J., Ellrott, K., Nellore, A., & Thompson, R. F. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/418129 · Cited by 7
Hu, Y., Zhao, F., Graff, J. N., Chen, C., Zhao, X., THOMAS, G. V., Wu, H., Kardosh, A., Mills, G. B., Alumkal, J. J., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.08.593181 · Cited by 8
“Existing evidence has suggested that tumors with a higher expression of genes associated with IFN-γ signaling have a better response to ICB, such as anti-CTLA4 and anti-PD1/PD-L1 30, 56, 57, 58 .”
BackgroundInhibition of anti-tumor immunity by melanoma cell-derived Activin-A depends on STING
Pinjušić, K., Ambrosini, G., Lourenço, J., Fournier, N., Iseli, C., Guex, N., Egorova, O., Nassiri, S., & Constam, D. B. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1335207 · Cited by 6
Ataherian, M. R., Hafezi, N., Ferdosi-Shahandashti, E., & Abdinia, F. S. (2025) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2024.0259 · Cited by 6
“Another noteworthy fi nding pertains to the certain onco-lytic viruses, particularly the herpes simplex virus (HSV), which has been shown to induce high levels of IFN-c secretion within the TME.”
InfluentialThe MLL3/GRHL2 complex regulates malignant transformation and anti-tumor immunity in squamous cancer
Nam, C., Huang, G., Zheng, Y., Zhao, H., Pan, Y., Hu, B., Wenger, T. A., Van, H. T., Xu, L., Li, E., et al. (2025) · The Journal of Experimental Medicine · doi:10.1084/jem.20240758 · Cited by 7
“Notably, the efficacy of ICB therapy depends crucially on tumor-infiltrating T cells (Litchfield et al., 2021; Gao et al., 2016; Zaretsky et al., 2016; Tumeh et al., 2014; Hellmann et al., 2018).”
Self-citationCytokine-mediated regulation of immune cell metabolic pathways in the tumor microenvironment
Mamalo, A. S., Pashaei, M. R., Valilo, M., & Ojarudi, M. (2025) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-025-04133-8 · Cited by 6
“Also, mice lacking expression of the IFN-γ receptor gene treated with anti-CTLA-4 had significantly higher tumor growth rates than mice with intact expression of the IFN-γ receptor gene (Gao et al. 2016).”
Clinical Utility of IFIT Proteins in Human Malignancies
Parsyan, A. E., Kochiyanil, A., Bonvissuto, A. C., Bhat, V., & Allan, A. L. (2025) · Biomedicines · doi:10.3390/biomedicines13061435 · Cited by 6
“Genomic defects in IFN pathway genes, including IFIT2, have been commonly observed in patients with poor responses to immunotherapy [22], suggesting that IFIT2 can be used to predict responses to immunotherapy [49] and targeted therapy.”
InfluentialPD-1 regulates tumor-infiltrating CD8+ T cells in both a cell-intrinsic and a cell-extrinsic fashion
Pauken, K. E., Markson, S. C., Conway, T. S., Juneja, V. R., Shahid, O., Burke, K. P., Rowe, J. H., Nguyen, T. H., Collier, J. L., Walsh, J. M. L., et al. (2025) · The Journal of Experimental Medicine · doi:10.1084/jem.20230542 · Cited by 6
Jessel, M.-D., McGreevy, O., McReynolds, L., Dahal, L. N., Gilbert, T. M., Malik, H., Goldring, C. E., & Randle, L. E. (2025) · Clinical & Translational Immunology · doi:10.1002/cti2.70057 · Cited by 6
“99 Tumor cells may also secrete exosomal PD-L1 to peripheral blood to inhibit T cell function systemically 100 and exhibit oncogenic mutations (e.g. mitogen-activated protein kinase and epidermal growth factor receptor pathway alterations), 98 which contribute to immunosuppression.”
Mikulak, J., Supino, D., Marzano, P., Terzoli, S., Carriero, R., Cazzetta, V., Piazza, R., Bruni, E., Kunderfranco, P., Donato, A., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci190778 · Cited by 6
ST6GAL1-mediated sialylation inhibits the antitumor immune response in colorectal cancer
Shi, Y., Peng, Z., Pan, Z., Duan, J., Wang, Z., Guan, Q., Fang, Y., & Tang, B. (2025) · Cellular Oncology · doi:10.1007/s13402-025-01118-w · Cited by 6
“IFN signaling is required to trigger antitumorigenic immunity [34].”
Mechanisms of Resistance to Chimeric Antigen Receptor T Cell Therapy
Johnson, G. A., & Locke, F. L. (2023) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2023.07.003 · Cited by 6
Song, L., Yang, Y., & Tian, X. (2024) · Cancer Drug Resistance · doi:10.20517/cdr.2023.150 · Cited by 5
Genomics-based immuno-oncology: bridging the gap between immunology and tumor biology
DiNatale, R. G., Hakimi, A. A., & Chan, T. A.-T. (2020) · Human Molecular Genetics · doi:10.1093/hmg/ddaa203 · Cited by 6
Kim, Y., Kim, K., Seo, S. Y., Yu, J., Kim, I. H., Kim, H. J., Park, C., Lee, K. H., Choi, J., Song, M. S., et al. (2021) · Animal Cells and Systems · doi:10.1080/19768354.2021.1954550 · Cited by 6
“Also, several studies reported that the loss of interferon-γ and antigen-presenting pathway genes in cancer cells causes resistance to PD-1 and anti-CTLA-4 therapies (Gao et al. 2016; Zaretsky et al. 2016).”
BackgroundMejía-Hernández, J. O., Keam, S. P., Saleh, R., Muntz, F., Fox, S. B., Byrne, D. J., Kogan, A., Pang, L., Huynh, J., Litchfield, C., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05211-y · Cited by 7
Wan, Q., Deng, Y., Wei, R., Ma, K., Tang, J., & Deng, Y. (2024) · Aging · doi:10.18632/aging.205606 · Cited by 6
Kim, Y., Gil, J., Plá, I., Sánchez, A., Betancourt, L. H., Lee, B., Appelqvist, R., Ingvar, C., Lundgren, L., Olsson, H. L., et al. (2020) · Cancers · doi:10.3390/cancers12030767 · Cited by 6
PREDICTIVE RESPONSE MARKERS FOR IMMUNE RESPONSE BLOCKS
Janus, G. A., Iyevleva, A. G., Suspitsyn, E. N., Tiurin, V. I., Валерьевич, Б. И., Gorustovich, O. A., Imyanitov, E., Kholmatov, M. M., Laidus, T. A., Chuynyshena, S., et al. (2020) · Siberian Journal of Oncology · doi:10.21294/1814-4861-2020-19-4-123-131 · Cited by 7
Sinha, D., Smith, C., & Khanna, R. (2020) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2020.09.005 · Cited by 6
Future Strategies Involving Immune Checkpoint Inhibitors in Advanced Urothelial Carcinoma
Grisay, G., Pierrard, J., Confente, C., & Seront, E. (2020) · Current Treatment Options in Oncology · doi:10.1007/s11864-020-00799-9 · Cited by 7
Schmitt, M., Sinnberg, T. W., Niessner, H., Forschner, A., Garbe, C., Maček, B., & Nalpas, N. (2021) · Cancers · doi:10.3390/cancers13215411 · Cited by 6
“Besides the mutation in β2-microtubulin, the loss of the JAK-STAT pathway results in an acquired resistance due to the down-regulation of MHC-1 [18,19].”
BackgroundTrono, P., Sistigu, A., Palermo, B., Ciliberto, G., & Nisticò, P. (2017) · Emerging Topics in Life Sciences · doi:10.1042/etls20170068 · Cited by 6
Chen, P., Liu, Y., Zhao, J., Pang, X., Zhang, P., Hou, X., Chen, P., He, C., Wang, Z., & Chen, Z.-Y. (2018) · Biomaterials Science · doi:10.1039/c7bm01143a · Cited by 6
Self-citationKim, H. K., Joung, J., Choi, Y., Lee, S., Park, B. J., Choi, Y. S., Ryu, D., Nam, J., Lee, M.-S., Park, W., et al. (2020) · iScience · doi:10.1016/j.isci.2020.101386 · Cited by 6
“…(Hsu et al., 2018), (2) any alteration in the IFNg signalingpathway including expression of IFNg receptor or its post-translationalmodification (Gao et al., 2016; Garcia-Diaz et al., 2017), (3) IFNg-stimulated chemokine CXCL9 secretion from tumor cells throughM1macrophage-activatedNKcells in…”
BackgroundMemon, D., Rizvi, H. A., Fromm, G. J., Lihm, J., Schoenfeld, A. J., Sauter, J. L., Luo, J., Chow, A. T., Bhanot, U. K., McCarthy, C. G., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.07.21.452854 · Cited by 6
Li, C.-F., Bai, L., Wei, Y., Lee, H., Yang, R., Yao, J., Wang, H., Wang, Y., Chang, W., Shen, Y.-C., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.10.20.619300 · Cited by 6
Darawshy, F., Tsay, J.-C. J., Segal, L. N., & Pass, H. I. (2025) · Cancer Biomarkers · doi:10.1177/18758592251322045 · Cited by 5
Bhattacharya, P., Linnenbach, A. J., South, A. P., Martinez‐Outschoorn, U., Curry, J., Johnson, J. M., Harshyne, L. A., Mahoney, M. G., Luginbuhl, A., & Vadigepalli, R. (2025) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1013127 · Cited by 5
Tassinari, V., Kaciulis, M., Petrai, S., Stabile, H., Pernazza, A., Leopizzi, M., Maio, V. D., Belleudi, F., Ranieri, D., Mancini, V., et al. (2025) · JCI Insight · doi:10.1172/jci.insight.190244 · Cited by 5
IFN γ and the IFN γ Signaling Pathways in Merkel Cell Carcinoma
Song, L., Guan, J., Zhou, Q., Liu, W., Becker, J. C., & Deng, D. (2025) · Cancers · doi:10.3390/cancers17152547 · Cited by 5
“Resistance to anti-PD1 and anti-CTLA-4 therapies has recently been linked to IFN γ resistance, which protects tumors from cytokine-induced apoptosis, cell cycle arrest, and sustained IFN γ signaling that upregulates ligands for inhibitory T-cell receptors [74–76].”
Bauer, M., Vaxevanis, C., Jaekel, N., Hackl, H., Wilfer, A., Zoellig, C., Hämmerle, M., Müller‐Tidow, C., Al‐Ali, H. K., Seliger, B., et al. (2025) · Leukemia · doi:10.1038/s41375-025-02706-3 · Cited by 5
“Vice versa, the inhibition of the IFN-γ signaling resulted in phenotypically less exhausted tumor-in fi ltrating lymphocytes (TILs), but an impaired immune checkpoint (ICP) inhibition [12, 13].”
Hu, Y., Zhao, F., Graff, J. N., Chen, C., Zhang, Y., Stommel, J. M., Lee, J., Zangirolani, G. M., Rose, J., THOMAS, G. V., et al. (2025) · Cancer Research Communications · doi:10.1158/2767-9764.crc-25-0409 · Cited by 5
CRISPR screens define unified hallmarks of cancer cell-autonomous immune evasion
Huber, A., Djajawi, T. M., Rivera, S., Vervoort, S. J., & Kearney, C. J. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116738 · Cited by 5
Ning, Y., Lei, K. J., Gao, X., Kong, Y., Shan, Y., Tian, T., Cui, Z., & Ren, H. (2026) · Clinical and Translational Medicine · doi:10.1002/ctm2.70582 · Cited by 6
Insights into RAS-driven melanoma and its therapeutic implications
Chatziioannou, E., Lallas, K., Sinnberg, T. W., Niessner, H., Stratigos, A., Flatz, L., & Amaral, T. (2026) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2026.103090 · Cited by 5
Dendritic cell redundancy enables priming of anti-tumor CD4+ T cells in pancreatic cancer
Kureshi, C. T. S., Walsh, M. J., Kureshi, R., Cardot‐Ruffino, V., Agardy, D. A., Ali, L. R., Dougan, J. M., Li, Q., Shen, J., Zuo, C., et al. (2026) · Cancer Cell · doi:10.1016/j.ccell.2026.04.005 · Cited by 8
A Prognostic Model Using Immune-Related Genes for Colorectal Cancer
Feng, W., Zhang, Y., Liu, W., Wang, X., Lei, T., Yuan, Y., Chen, Z., & Wu, S. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.813043 · Cited by 5
“However, the objective response rate to ICIs is not ideal for many patients who experience drug resistance with time and who even become what is termed as “hyperprogressors” (Gao et al., 2016; Zaretsky et al., 2016; Kato et al., 2017).”
BackgroundIFN-γ Signaling Sensitizes Melanoma Cells to BH3 Mimetics
Ming, Z., Lim, S. Y., Stewart, A., Pedersen, B., Shklovskaya, E., Menzies, A. M., Carlino, M. S., Kefford, R. F., Lee, J., Scolyer, R. A., et al. (2023) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2023.01.017 · Cited by 5
Kefas, J., & Flynn, M. (2024) · Cancer Drug Resistance · doi:10.20517/cdr.2024.67 · Cited by 6
Zhao, Z., Xu, K., Hu, B., Jiang, Y., Xu, X., & Liu, Y. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1519498 · Cited by 5
HIV status alters immune cell infiltration and activation profile in women with breast cancer
Bauer, M., Santos, P. S. C., Wilfer, A., van den Berg, E. J., Zietsman, A., Vetter, M., Kaufhold, S., Wickenhauser, C., dos‐Santos‐Silva, I., Chen, W. C., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-59408-8 · Cited by 5
Chung, Y. M., Tsai, W.-B., Khan, P. P., Ma, J., Berek, J. S., Larrick, J. W., & Hu, M. C. ‐. (2022) · PubMed Central · Cited by 5
Liu, J., Zhang, X., Ren, Q., Song, C., Yu, J., Cai, Y., & Chen, D. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1484802 · Cited by 5
Safir, W., Malik, A., Saadia, H., Zahid, A., & Li, J. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1546062 · Cited by 5
Kalbasi, A. K., & Rengan, R. (2007) · Translational Lung Cancer Research · doi:10.21037/tlcr.2017.03.03 · Cited by 5
Yamaguchi, H., Hiroi, M., & Ohmori, Y. (2018) · Cytokine · doi:10.1016/j.cyto.2018.06.029 · Cited by 5
Singh, P., SOUZA, P. D., Scott, K. F., Hall, B. M., Verma, N. D., Becker, T. M., Toh, J. W. T., Sajinovic, M., & Spring, K. J. (2019) · Translational Medicine Communications · doi:10.1186/s41231-019-0032-9 · Cited by 5
“found that the melanoma tumors that were resistant to ipilimumab therapy had defects in IFN-γ pathway genes [46].”
BackgroundGenetic Screening for Novel Regulators of Immune Checkpoint Molecules
Arens, R., & Scheeren, F. A. (2020) · Trends in Immunology · doi:10.1016/j.it.2020.06.005 · Cited by 6
Expression of T helper 1-associated lncRNAs in breast cancer
Sattari, A., Hussen, B. M., Ghafouri‐Fard, S., Alihashemi, A., Omrani, M. D., Zekri, A., & Taheri, M. N. (2021) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2021.104619 · Cited by 5
Landscape of Immunotherapy in Genitourinary Malignancies
Ravindranathan, D., Alhalabi, O., Rafei, H., Shah, A. Y., & Bilen, M. A. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-79308-1_5 · Cited by 6
Cerqueira, O. L. D., Antunes, F., de Assis, N. G., Cardoso, E. C., Clavijo-Salomon, M. A., Domingues, A. C. M., Tessarollo, N. G., & Strauss, B. E. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.777775 · Cited by 5
“Analysis of the TCGA dataset and studies in vitro and in vivo showed that nearly 30% of melanoma samples present mutations in the interferon signaling pathway, which is associated with shorter overall survival (Gao et al., 2016).”
BackgroundIMMUNE REGULATORY FUNCTION OF INTERFERON-GAMMA IN ACUTE LEUKEMIA
Choudhary, A. (2021) · Indian Journal Of Applied Research · doi:10.36106/ijar/1502576 · Cited by 5
Reva, B. A., Omelchenko, T., Calinawan, A. P., Nair, S. S., Schadt, E. E., & Tewari, A. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.10.19.345629 · Cited by 5
Yan, D., Yi, W., Wu, T., Hu, S., Ding, Y., Qian, X., Zhao, Z., Wang, D., Xu, H., Cai, Y., et al. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.114324 · Cited by 5
Cheng, X., Luo, K., Gao, Y., Wang, R., Liu, S., Li, Q., Zhou, S., Yang, H., Chen, B., Liu, Q., et al. (2025) · Annals of Medicine · doi:10.1080/07853890.2025.2576639 · Cited by 4
“Its role in shaping the tumour microenvironment can be improved by the therapeutic efficacy of immunotherapy by modulating immune cell responses [43].”
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
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
