Data from Tumor-Infiltrating and Peripheral Blood T-cell Immunophenotypes Predict Early Relapse in Localized Clear Cell Renal Cell Carcinoma

作者：Nicolás A. Giraldo, Étienne Becht, Yann Vano, Florent Petitprez, Laetitia Lacroix, Pierre Validire, Rafael Sanchez‐Salas, Alexandre Ingels, Stéphane Oudard, Audrey Moatti, Bénédicte Buttard, Sarah Bourass, Claire Germain, Xavier Cathelineau, Wolf H. Fridman, Catherine Sautès‐Fridman · 年份：2023 · DOI：10.1158/1078-0432.c.6526922.v1 · 被引用次数：1 · 研究领域：Cancer Immunotherapy and Biomarkers、Renal cell carcinoma treatment、Cancer Genomics and Diagnostics

<div>AbstractPurpose: The efficacy of PD-1 checkpoint blockade as adjuvant therapy in localized clear cell renal cell carcinoma (ccRCC) is currently unknown. The identification of tumor microenvironment (TME) prognostic biomarkers in this setting may help define which patients could benefit from checkpoint blockade and uncover new therapeutic targets.Experimental Design: We performed multiparametric flow cytometric immunophenotypic analysis of T cells isolated from tumor tissue [tumor-infiltrating lymphocytes (TIL)], adjacent non-malignant renal tissue [renal-infiltrating lymphocytes (RIL)], and peripheral blood lymphocytes (PBL), in a cohort of patients (n = 40) with localized ccRCC. Immunophenotypic data were integrated with prognostic and histopathologic variables, T-cell receptor (TCR) repertoire analysis of sorted CD8+PD-1+ TILs, tumor mRNA expression, and digital quantitative immunohistochemistry.Results: On the basis of TIL phenotypic characterization, we identified three dominant immune profiles in localized ccRCC: (i) immune-regulated, characterized by polyclonal/poorly cytotoxic CD8+PD-1+Tim-3+Lag-3+ TILs and CD4+ICOS+ cells with a Treg phenotype (CD25<sup...