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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11510%2F24%3A10475558" target="_blank" >RIV/00216208:11510/24:10475558 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/24:10475558 RIV/00216208:11130/24:10475558 RIV/00064203:_____/24:10475558 RIV/00064165:_____/24:10475558

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=bXh2DvJQHa" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=bXh2DvJQHa</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.tranon.2024.101891" target="_blank" >10.1016/j.tranon.2024.101891</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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(+) 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 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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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(+) 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 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Translational Oncology

ISSN

1936-5233

e-ISSN

—

Svazek periodika

42

Číslo periodika v rámci svazku

April

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

101891

Kód UT WoS článku

001180356900001

EID výsledku v databázi Scopus

2-s2.0-85183991440