Distinct leukocyte populations and cytokine secretion profiles define tumoral and peritumoral areas in renal cell carcinoma.
Details
Download: 38310685_BIB_B55655674776.pdf (3481.27 [Ko])
State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
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
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
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 10:49
Last modification date
09/08/2024 15:04