Beyond suppression: the paradox of JAK inhibitors as amplifiers of cancer immunotherapy

Beyond suppression: the paradox of JAK inhibitors as amplifiers of cancer immunotherapy

  • Mumm, J. B. et al. IL-10 elicits IFNγ-dependent tumor immune surveillance. Cancer Cell 20, 781–796 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Qiao, J. et al. Targeting tumors with IL-10 prevents dendritic cell-mediated CD8+ T cell apoptosis. Cancer Cell 35, 901–915.e4 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Teijaro, J. R. et al. Persistent LCMV infection is controlled by blockade of type I interferon signaling. Science 340, 207 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wilson, E. B. et al. Blockade of chronic type I interferon signaling to control persistent LCMV infection. Science 340, 202–207 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Perez-Ruiz, E. et al. Prophylactic TNF blockade uncouples efficacy and toxicity in dual CTLA-4 and PD-1 immunotherapy. Nature 569, 428–432 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bertrand, F. et al. Blocking tumor necrosis factor α enhances CD8 T-cell-dependent immunity in experimental melanoma. Cancer Res. 75, 2619–2628 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Benci, J. L. et al. Tumor interferon signaling regulates a multigenic resistance program to immune checkpoint blockade. Cell 167, 1540–1554.e12 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lu, C., Talukder, A., Savage, N. M., Singh, N. & Liu, K. JAK–STAT-mediated chronic inflammation impairs cytotoxic T lymphocyte activation to decrease anti-PD-1 immunotherapy efficacy in pancreatic cancer. Oncoimmunology 6, e1291106 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Du, W.-Y. et al. Janus kinase inhibitor overcomes resistance to immune checkpoint inhibitor treatment in peritoneal dissemination of gastric cancer in C57BL/6 J mice. Gastric Cancer 27, 971–985 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zak, J. et al. JAK inhibition enhances checkpoint blockade immunotherapy in patients with Hodgkin lymphoma. Science 384, eade8520 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mathew, D. et al. Combined JAK inhibition and PD-1 immunotherapy for non-small cell lung cancer patients. Science 384, eadf1329 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Debureaux, P. E., Arrondeau, J., Bouscary, D. & Goldwasser, F. Nivolumab combined with ruxolitinib: antagonism or synergy? Ann. Oncol. 29, 1334–1335 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Nijland, M. et al. Combined PD-1 and JAK1/2 inhibition in refractory primary mediastinal B-cell lymphoma. Ann. Hematol. 97, 905–907 (2018).

    CAS 
    PubMed 

    Google Scholar
     

  • Tolu, S. S. et al. Combination JAK inhibition and immune checkpoint blockade for the treatment of 9p amplified Lymphomas. Blood 144, 336 (2024).

    Article 

    Google Scholar
     

  • Elli, E. M., Baratè, C., Mendicino, F., Palandri, F. & Palumbo, G. A. Mechanisms underlying the anti-inflammatory and immunosuppressive activity of ruxolitinib. Front. Oncol. 9, 1186 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Patel, M. R. et al. JAK/STAT inhibition with ruxolitinib enhances oncolytic virotherapy in non-small cell lung cancer models. Cancer Gene Ther. 26, 411–418 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wang, S.-W. et al. AZD1480, a JAK inhibitor, inhibits cell growth and survival of colorectal cancer via modulating the JAK2/STAT3 signaling pathway. Oncol. Rep. 32, 1991–1998 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lee, S. et al. Ruxolitinib significantly enhances in vitro apoptosis in Hodgkin lymphoma and primary mediastinal B-cell lymphoma and survival in a lymphoma xenograft murine model. Oncotarget 9, 9776–9788 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Moskowitz, A. J. et al. A phase 2 biomarker-driven study of ruxolitinib demonstrates effectiveness of JAK/STAT targeting in T-cell lymphomas. Blood 138, 2828–2837 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Govaerts, I., Jacobs, K., Vandepoel, R. & Cools, J. JAK/STAT pathway mutations in T-ALL, including the STAT5B N642H mutation, are aensitive to JAK1/JAK3 inhibitors. HemaSphere 3, e313 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Datta, J. et al. Combined MEK and STAT3 inhibition uncovers stromal plasticity by enriching for cancer-associated fibroblasts with mesenchymal stem cell-like features to overcome immunotherapy resistance in pancreatic cancer. Gastroenterology 163, 1593–1612 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Qureshy, Z. et al. STAT3 activation as a predictive biomarker for ruxolitinib response in head and neck cancer. Clin. Cancer Res. 28, 4737–4746 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tavallai, M., Booth, L., Roberts, J. L., Poklepovic, A. & Dent, P. Rationally repurposing ruxolitinib (Jakafi®) as a solid tumor therapeutic. Front. Oncol. 6, 142 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wei, X.-H. & Liu, Y.-Y. Potential applications of JAK inhibitors, clinically approved drugs against autoimmune diseases, in cancer therapy. Front. Pharmacol. 14, 1326281 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Van Den Neste, E. et al. A phase II study of the oral JAK1/JAK2 inhibitor ruxolitinib in advanced relapsed/refractory Hodgkin lymphoma. Haematologica 103, 840–848 (2018).

    Article 
    PubMed 

    Google Scholar
     

  • Gillessen, S. et al. JAK inhibition with ruxolitinib in relapsed or refractory classical Hodgkin lymphoma: final results of a phase II, open label, multicentre clinical trial (JeRiCHO). Eur. J. Haematol. 109, 728–735 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kim, S. J. et al. Ruxolitinib shows activity against Hodgkin lymphoma but not primary mediastinal large B-cell lymphoma. BMC Cancer 19, 1080 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jardim, D. L., Goodman, A., de Melo Gagliato, D. & Kurzrock, R. The challenges of tumor mutational burden as an immunotherapy biomarker. Cancer Cell 39, 154–173 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chan, T. A. et al. Development of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic. Ann. Oncol. 30, 44–56 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Schreiber, R. D., Old, L. J. & Smyth, M. J. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science 331, 1565–1570 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zaretsky, J. M. et al. Mutations associated with acquired resistance to PD-1 blockade in melanoma. N. Engl. J. Med. 375, 819–829 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Weichselbaum, R. R. et al. An interferon-related gene signature for DNA damage resistance is a predictive marker for chemotherapy and radiation for breast cancer. Proc. Natl. Acad. Sci. USA 105, 18490–18495 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Benci, J. L. et al. Opposing functions of interferon coordinate adaptive and innate immune responses to cancer immune checkpoint blockade. Cell 178, 933–948.e14 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shen, H. et al. Selective suppression of melanoma lacking IFN-γ pathway by JAK inhibition depends on T cells and host TNF signaling. Nat. Commun. 13, 5013 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lee, H.-J. et al. Drug resistance via feedback activation of Stat3 in oncogene-addicted cancer cells. Cancer Cell 26, 207–221 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Karjalainen, R. et al. JAK1/2 and BCL2 inhibitors synergize to counteract bone marrow stromal cell-induced protection of AML. Blood 130, 789–802 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Han, E. S. et al. Ruxolitinib synergistically enhances the anti-tumor activity of paclitaxel in human ovarian cancer. Oncotarget 9, 24304–24319 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Reeves, P. M. et al. Ruxolitinib sensitizes ovarian cancer to reduced dose Taxol, limits tumor growth and improves survival in immune competent mice. Oncotarget 8, 94040–94053 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Stevens, L. E. et al. JAK–STAT signaling in inflammatory breast cancer enables chemotherapy-resistant cell states. Cancer Res. 83, 264–284 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hu, Y. et al. Inhibition of the JAK/STAT pathway with ruxolitinib overcomes cisplatin resistance in non-small-cell lung cancer NSCLC. Apoptosis 19, 1627–1636 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Landen, C. N. et al. Phase I and randomized phase II study of ruxolitinib with frontline neoadjuvant therapy in advanced ovarian cancer: an NRG oncology group study. J. Clin. Oncol. 42, 2537–2545 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hurwitz, H. et al. Ruxolitinib + capecitabine in advanced/metastatic pancreatic cancer after disease progression/intolerance to first-line therapy: JANUS 1 and 2 randomized phase III studies. Invest. New Drugs 36, 683–695 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Escobar-Zarate, D., Liu, Y. P., Suksanpaisan, L., Russell, S. J. & Peng, K. W. Overcoming cancer cell resistance to VSV oncolysis with JAK1/2 inhibitors. Cancer Gene Ther. 20, 582–589 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ghonime, M. G. & Cassady, K. A. Combination therapy using ruxolitinib and oncolytic HSV renders resistant MPNSTs susceptible to virotherapy. Cancer Immunol. Res. 6, 1499–1510 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Xu, L. et al. Inhibition of IL-6-JAK/Stat3 signaling in castration-resistant prostate cancer cells enhances the NK cell-mediated cytotoxicity via alteration of PD-L1/NKG2D ligand levels. Mol. Oncol. 12, 269–286 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shen, M. et al. Inhibition of ATM reverses EMT and decreases metastatic potential of cisplatin-resistant lung cancer cells through JAK/STAT3/PD-L1 pathway. J. Exp. Clin. Cancer Res. 38, 149 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chen, H. et al. Ruxolitinib reverses checkpoint inhibition by reducing programmed cell death ligand-1 (PD-L1) expression and increases anti-tumour effects of T cells in multiple myeloma. Br. J. Haematol. 192, 568–576 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cao, Y. et al. Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): a multicenter, single-blind, randomized controlled trial. J. Allergy Clin. Immunol. 146, 137–146.e3 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kumar, A., Taghi Khani, A., Sanchez Ortiz, A. & Swaminathan, S. GM-CSF: a double-edged sword in cancer immunotherapy. Front. Immunol. 13, 901277 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bayne, L. J. et al. Tumor-derived granulocyte–macrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer. Cancer Cell 21, 822–835 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pylayeva-Gupta, Y., Lee, K. E., Hajdu, C. H., Miller, G. & Bar-Sagi, D. Oncogenic Kras-induced GM-CSF production promotes the development of pancreatic neoplasia. Cancer Cell 21, 836–847 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huseni, M. A. et al. CD8+ T cell-intrinsic IL-6 signaling promotes resistance to anti-PD-L1 immunotherapy. Cell Rep. Med. 4, 100878 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Adlung, L. et al. Protein abundance of AKT and ERK pathway components governs cell type-specific regulation of proliferation. Mol. Syst. Biol. 13, 904 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ebisuya, M., Kondoh, K. & Nishida, E. The duration, magnitude and compartmentalization of ERK MAP kinase activity: mechanisms for providing signaling specificity. J. Cell Sci. 118, 2997–3002 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mostafavi, S. et al. Parsing the interferon transcriptional network and its disease associations. Cell 164, 564–578 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Baker, B. J., Akhtar, L. N. & Benveniste, E. N. SOCS1 and SOCS3 in the control of CNS immunity. Trends Immunol. 30, 392–400 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cheemalavagu, N. et al. Predicting gene-level sensitivity to JAK–STAT signaling perturbation using a mechanistic-to-machine learning framework. Cell Syst. 15, 37–48.e4 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Vian, L. et al. JAK inhibition differentially affects NK cell and ILC1 homeostasis. Front. Immunol. 10, 2972 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hoang, T. N. et al. Baricitinib treatment resolves lower-airway macrophage inflammation and neutrophil recruitment in SARS-CoV-2-infected rhesus macaques. Cell 184, 460–475.e21 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bronte, V. et al. Baricitinib restrains the immune dysregulation in patients with severe COVID-19. J. Clin. Invest. 130, 6409–6416 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Choi, J. et al. Pharmacologic blockade of JAK1/JAK2 reduces GvHD and preserves the graft-versus-leukemia effect. PLoS One 9, e109799 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Carniti, C. et al. Pharmacologic inhibition of JAK1/JAK2 signaling reduces experimental murine acute GVHD while preserving GVT effects. Clin. Cancer Res. 21, 3740–3749 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kenderian, S. S. et al. Ruxolitinib prevents cytokine release syndrome after CART cell therapy without impairing the anti-tumor effect in a xenograft model. Blood 128, 652 (2016).

    Article 

    Google Scholar
     

  • Mestre-Durán, C. et al. Ruxolitinib does not completely abrogate the functional capabilities of TLR4/9 ligand-activated NK cells. Front. Immunol. 13, 1045316 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • He, K. et al. G-CSF/GM-CSF-induced hematopoietic dysregulation in the progression of solid tumors. FEBS Open. Bio 12, 1268–1285 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wlassits, R., Müller, M., Fenzl, K. H., Lamprecht, T. & Erlacher, L. JAK-inhibitors—a story of success and adverse events. Open. Access. Rheumatol.: Res. Rev. 16, 43–53 (2024).

    Article 
    CAS 

    Google Scholar
     

  • Ytterberg, S. R. et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N. Engl. J. Med. 386, 316–326 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cohen, S. B. et al. Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELECT phase III clinical programme. Ann. Rheum. Dis. 80, 304 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bukali, L. et al. Transient JAK/STAT inhibition by ruxolitinib modulates malaria-specific CD4+ T cell responses and enhances recall immunity in volunteers experimentally infected with Plasmodium falciparum. Preprint at medRxiv https://doi.org/10.1101/2025.04.09.25325416 (2025).

  • Pai, C.-C. S. et al. Clonal deletion of tumor-specific T cells by interferon-γ confers therapeutic resistance to combination immune checkpoint blockade. Immunity 50, 477–492.e8 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Arias-Badia, M. et al. Sequential JAK inhibition enhances antitumor immunity after combined anti-PD-1 and anti-CTLA4. JCI Insight 10, e187921 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shimabukuro-Vornhagen, A. et al. Cytokine release syndrome. J. Immunother. Cancer 6, 56 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Le, R. Q. et al. FDA approval summary: tocilizumab for treatment of chimeric antigen receptor T cell-induced severe or life-threatening cytokine release syndrome. Oncologist 23, 943–947 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zi, F. M., Ye, L. L., Zheng, J. F., Cheng, J. & Wang, Q. M. Using JAK inhibitor to treat cytokine release syndrome developed after chimeric antigen receptor T cell therapy for patients with refractory acute lymphoblastic leukemia: a case report. Medicine 100, e25786 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pan, B. et al. PD-1 antibody and ruxolitinib enhances graft-versus-lymphoma effect without increasing acute graft-versus-host disease in mice. Am. J. Transplant. 21, 503–514 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Xu, N. et al. Ruxolitinib reduces severe CRS response by suspending CAR-T cell function instead of damaging CAR-T cells. Biochem. Biophys. Res. Commun. 595, 54–61 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Leclercq, G. et al. Novel strategies for the mitigation of cytokine release syndrome induced by T cell engaging therapies with a focus on the use of kinase inhibitors. Oncoimmunology 11, 2083479 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Masucci, C. et al. Case report: avelumab and ruxolitinib to manage polycythemia vera and secondary metastatic Merkel cell carcinoma: a possible successful combination. Front. Oncol. 13, 1212638 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dougan, M., Luoma, A. M., Dougan, S. K. & Wucherpfennig, K. W. Understanding and treating the inflammatory adverse events of cancer immunotherapy. Cell 184, 1575–1588 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huang, Z. et al. IFNAR1 signaling in NK cells promotes persistent virus infection. Sci. Adv. 7, eabb8087 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cheng, L. et al. Type I interferons suppress viral replication but contribute to T cell depletion and dysfunction during chronic HIV-1 infection. JCI Insight 2, e94366 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhen, A. et al. Targeting type I interferon-mediated activation restores immune function in chronic HIV infection. J. Clin. Invest. 127, 260–268 (2017).

    Article 
    PubMed 

    Google Scholar
     

  • Wu, T. et al. The TCF1–Bcl6 axis counteracts type I interferon to repress exhaustion and maintain T cell stemness. Sci. Immunol. 1, eaai8593 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cunningham, C. R. et al. Type I and type II interferon coordinately regulate suppressive dendritic cell fate and function during viral persistence. PLoS Pathog. 12, e1005356 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huang, Z. et al. IL-27 promotes the expansion of self-renewing CD8 T cells in persistent viral infection. J. Exp. Med. 216, 1791–1808 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lukhele, S. et al. The transcription factor IRF2 drives interferon-mediated CD8+ T cell exhaustion to restrict anti-tumor immunity. Immunity 55, 2369–2385.e10 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Moseman, E. A., Wu, T., de la Torre, J. C., Schwartzberg, P. L. & McGavern, D. B. Type I interferon suppresses virus-specific B cell responses by modulating CD8+ T cell differentiation. Sci. Immunol. 1, eaah3565 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ng, C. T. et al. Blockade of interferon β, but not interferon α, signaling controls persistent viral infection. Cell Host Microbe 17, 653–661 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fallet, B. et al. Interferon-driven deletion of antiviral B cells at the onset of chronic infection. Sci. Immunol. 1, eaah6817 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sammicheli, S. et al. Inflammatory monocytes hinder antiviral B cell responses. Sci. Immunol. 1, eaah6789 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Boukhaled, G. M. et al. Pre-encoded responsiveness to type I interferon in the peripheral immune system defines outcome of PD1 blockade therapy. Nat. Immunol. 23, 1273–1283 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Minn, A. J. & Wherry, E. J. Combination cancer therapies with immune checkpoint blockade: convergence on interferon signaling. Cell 165, 272–275 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Qiu, J. et al. Cancer cells resistant to immune checkpoint blockade acquire interferon-associated epigenetic memory to sustain T cell dysfunction. Nat. Cancer 4, 43–61 (2023).

    CAS 
    PubMed 

    Google Scholar
     

  • Jacquelot, N. et al. Sustained type I interferon signaling as a mechanism of resistance to PD-1 blockade. Cell Res. 29, 846–861 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhu, C. et al. Development and validation of an interferon signature predicting prognosis and treatment response for glioblastoma. Oncoimmunology 8, e1621677 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Silginer, M. et al. Autocrine activation of the IFN signaling pathway may promote immune escape in glioblastoma. Neuro Oncol. 19, 1338–1349 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Duarte, C. W. et al. Expression signature of IFN/STAT1 signaling genes predicts poor survival outcome in glioblastoma multiforme in a subtype-specific manner. PLoS One 7, e29653 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Memon, D. et al. Clinical and molecular features of acquired resistance to immunotherapy in non-small cell lung cancer. Cancer Cell 42, 209–224.e9 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shi, Y. et al. Acquired resistance to PD-L1 inhibition enhances a type I IFN-regulated secretory program in tumors. EMBO Rep. 26, 521–559 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zemek, R. M. et al. Temporally restricted activation of IFNβ signaling underlies response to immune checkpoint therapy in mice. Nat. Commun. 13, 4895 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Srivastava, S., Koch, M. A., Pepper, M. & Campbell, D. J. Type I interferons directly inhibit regulatory T cells to allow optimal antiviral T cell responses during acute LCMV infection. J. Exp. Med. 211, 961–974 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Osokine, I. et al. Type I interferon suppresses de novo virus-specific CD4 TH1 immunity during an established persistent viral infection. Proc. Natl Acad. Sci. USA 111, 7409 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dai, Y. et al. Humoral determinants of checkpoint immunotherapy. Nature 644, 527–536 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar