Distinct leukocyte populations and cytokine secretion profiles define tumoral and peritumoral areas in renal cell carcinoma.

Details

Serval ID
serval:BIB_B55655674776
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Distinct leukocyte populations and cytokine secretion profiles define tumoral and peritumoral areas in renal cell carcinoma.
Journal
Translational oncology
Author(s)
Borcinova M., Bartolini R., Foley L.K., Novak V., Taborska P., Stakheev D., Rataj M., Smrz D., Fialova M., Hacek J., Komarc M., Vesely S., Babjuk M., Striz I., Bartunkova J., Buchler T., Ozaniak Strizova Z.
ISSN
1936-5233 (Print)
ISSN-L
1936-5233
Publication state
Published
Issued date
04/2024
Peer-reviewed
Oui
Volume
42
Pages
101891
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Renal 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 <sup>+</sup> T cells primarily employed Fas Ligand for cytotoxicity, while CD4 <sup>+</sup> T cells relied on CD107a. In addition, a statistically significant negative correlation between patient mortality and the presence of CD4 <sup>+</sup> CD107 <sup>+</sup> pTILs was demonstrated. The engagement with the PD-1/PD-L1 pathway was also more evident in CD4 <sup>+</sup> and CD8 <sup>+</sup> 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 stronger responses to stimulation than TILs and pTILs. Our results suggest that tumor and peritumoral T cells exhibit limited responsiveness to additional activation signals, while peripheral T cells retain their capacity to respond to stimulatory signals.
Keywords
CAFs, CD8 T cells, Kidney cancer, Pecam-1, Rcc tme, Renal carcinoma immunotherapy, Tumor immune microenvironment, Tumor-infiltrating lymphocytes, cytotoxicity, kidney cancer cytokines, peritumoral tissue, PECAM-1, RCC TME
Pubmed
Web of science
Open Access
Yes
Create date
09/02/2024 11:49
Last modification date
06/04/2024 7:24
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