Immunotherapeutic therapies such as immune checkpoint inhibitors have been used in patients with renal cell carcinoma (RCC). To overcome therapeutic resistance or identify predictive markers, a comprehensive understanding of the immunologic condition in the tumor microenvironment is important. We reviewed the latest scientific findings on the comprehensive immunologic condition within the tumor microenvironment in patients with RCC and its clinical significance. The immunologic condition evaluated by 3 different methods (flow cytometry, mass cytometry, and next-generation sequencing) in 4 different cohorts of patients with RCC could commonly divide the immunologic condition into 2 or 3 groups, all of which were significantly correlated with tumor aggressiveness and patient prognosis. In particular, patients with high T-cell infiltration and immunosuppressive cells including regulatory T cells had the worst prognosis in each cohort. This classification correlated with angiogenesis and metabolism and glycolysis, and it suggested that distinct biology exists in each immunologic classification. Moreover, around 20% to 30% of the RCC patients had intratumor immunologic diversity within each individual; this might help in understanding the presence of radiologic heterogeneity for immunotherapies. In conclusion, a comprehensive understanding of the immune condition is needed for the upcoming era of novel cancer immunotherapy using not only genetic but also phenotypic and functional classifications.
Keywords: Exhausted T cells; Heterogeneity; Immunotherapy; Macrophage; Regulatory T cells.
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