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Emerging resistance vs. losing response to immune check point inhibitors in renal cell carcinoma: two differing phenomena

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Cancer Drug Resistance 2023年第3期6卷 642-655页

作者： Arya Mariam Roy Saby George Division of Hematology and Oncology Department of Internal MedicineRoswell Park Comprehensive Cancer CenterBuffaloNY 14203USA

The introduction of immune checkpoint inhibitor (ICI) has revolutionized the treatment of metastatic renal cell carcinoma (mRCC) and has dramatically improved the outcomes of patients. The use of monotherapy or combinations of ICIs targeting PD-1/PD-L1 and CTLA-4, as well as the addition of ICIs with tyrosine kinase inhibitors, has significantly enhanced the overall survival of mRCC patients. Despite these promising results, there remains a subset of patients who either do not respond to treatment (primary resistance) or develop resistance to therapy over time (acquired resistance). Understanding the mechanisms underlying the development of resistance to ICI treatment is crucial in the management of mRCC, as they can be used to identify new targets for innovative therapeutic strategies. Currently, there is an unmet need to develop new predictive and prognostic biomarkers that can aid in the development of personalized treatment options for mRCC patients. In this review, we summarize several mechanisms of ICI resistance in RCC, including alterations in tumor microenvironment, upregulation of alternative immune checkpoint pathways, and genetic and epigenetic changes. Additionally, we highlight potential strategies that can be used to overcome resistance, such as combination therapy, targeted therapy, and immune modulation.

关键词： Renal cell carcinoma immunotherapy immune checkpoint inhibitors primary resistance acquired resistance immune exhaustion markers immunosuppressive tumor microenvironment

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