Distinct leukocyte populations and cytokine secretion profiles define tumoral and peritumoral areas in renal cell carcinoma
Transl Oncol. 2024 Feb 3;42:101891. doi: 10.1016/j.tranon.2024.101891. Online ahead of print.ABSTRACTRenal cell carcinoma (RCC) is a common malignancy frequently diagnosed at the metastatic stage. We performed a comprehensive analysis of the tumor immune microenvironment (TIME) in RCC patients, including the peritumoral tissue microenvironment, to characterize the phenotypic patterns and functional characteristics of infiltrating immune cells. T cells from various compartments (peripheral blood, tumor, peritumoral area, and adjacent healthy renal tissue) were assessed using flow cytometry and Luminex analyses, both before and after T cell-specific stimulation, to evaluate activation status and migratory potential. Our findings demonstrated that tumor-infiltrating lymphocytes (TILs) exhibited heightened cytokine production compared to peritumoral T cells (pTILs), acting as the primary source of cytotoxic markers (IFN-γ, granzyme B, and FasL). CD8+ T cells primarily employed Fas Ligand for cytotoxicity, while CD4+ T cells relied on CD107a. In addition, a statistically significant negative correlation between patient mortality and the presence of CD4+CD107+ pTILs was demonstrated. The engagement with the PD-1/PD-L1 pathway was also more evident in CD4+ and CD8+ pTILs as opposed to TILs. PD-L1 expression in the non-leukocyte fraction of the tumor tissue was relatively lower than in their leukocytic counterparts and upon stimulation, peripheral blood T cells displayed much strong...
Source: Translational Oncology - Category: Cancer & Oncology Authors: Martina Borcinova Robin Bartolini Lily Koumbas Foley Vojtech Novak Pavla Taborska Dmitry Stakheev Michal Rataj Daniel Smrz Martina Fialova Jaromir Hacek Martin Komarc Stepan Vesely Marek Babjuk Ilja Striz Jirina Bartunkova Tomas Buchler Zuzana Ozaniak Str Source Type: research