Several clinicopathological features of clear cell renal cell carcinomas (ccRCC) contribute to make an "atypical" cancer, including resistance to chemotherapy, sensitivity to anti-angiogenesis therapy and ICIs despite a low mutational burden, and CD8+ T cell infiltration being the predictor for poor prognosis-normally CD8+ T cell infiltration is a good prognostic factor in cancer patients. These "atypical" features have brought researchers to investigate the molecular and immunological mechanisms that lead to the increased T cell infiltrates despite relatively low molecular burdens, as well as to decipher the immune landscape that leads to better response to ICIs. In the present study, we summarize the past and ongoing pivotal clinical trials of immunotherapies for ccRCC, emphasizing the potential molecular and cellular mechanisms that lead to the success or failure of ICI therapy. Single-cell analysis of ccRCC has provided a more thorough and detailed understanding of the tumor immune microenvironment and has facilitated the discovery of molecular biomarkers from the tumor-infiltrating immune cells. We herein will focus on the discussion of some major immune cells, including T cells and tumor-associated macrophages (TAM) in ccRCC. We will further provide some perspectives of using molecular and cellular biomarkers derived from these immune cell types to potentially improve the response rate to ICIs in ccRCC patients.
Cancers. 2021 Nov 22*** epublish ***
Myung-Chul Kim, Zeng Jin, Ryan Kolb, Nicholas Borcherding, Jonathan Alexander Chatzkel, Sara Moscovita Falzarano, Weizhou Zhang
Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA., Department of Pathology and Immunology, Washington University, St. Louis, MO 63110, USA., Department of Medicine Hematology and Oncology Division, University of Florida, Gainesville, FL 32610, USA.