Immunological features of clear-cell renal-cell carcinoma and resistance to immune checkpoint inhibitors



Summary

Clear-cell renal cell carcinoma (ccRCC) is characterized by immune infiltration, but often exhibits resistance to immune checkpoint inhibitors (ICIs). Several factors contribute to this paradox. While ccRCC displays high levels of PD-L1 expression and tumor-infiltrating lymphocytes, these lymphocytes can be dysfunctional due to factors like T-cell exhaustion and the presence of immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs). Furthermore, genomic alterations in ccRCC, such as VHL mutations, lead to HIF activation, which promotes angiogenesis and inhibits T-cell function. Understanding these complex immunological features is crucial for developing more effective immunotherapeutic strategies for ccRCC.

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