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

M. Borcinova, R. Bartolini, LK. Foley, V. Novak, P. Taborska, D. Stakheev, M. Rataj, D. Smrz, M. Fialova, J. Hacek, M. Komarc, S. Vesely, M. Babjuk, I. Striz, J. Bartunkova, T. Buchler, Z. Ozaniak Strizova

. 2024 ; 42 (-) : 101891. [pub] 20240203

Status neindexováno Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc24005524

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.

Citace poskytuje Crossref.org

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$a Renal cell carcinoma (RCC) is a common malignancy frequently diagnosed at the metastatic stage. We performed a comprehensive analysis of the tumor immune microenvironment (TIME) in RCC patients, including the peritumoral tissue microenvironment, to characterize the phenotypic patterns and functional characteristics of infiltrating immune cells. T cells from various compartments (peripheral blood, tumor, peritumoral area, and adjacent healthy renal tissue) were assessed using flow cytometry and Luminex analyses, both before and after T cell-specific stimulation, to evaluate activation status and migratory potential. Our findings demonstrated that tumor-infiltrating lymphocytes (TILs) exhibited heightened cytokine production compared to peritumoral T cells (pTILs), acting as the primary source of cytotoxic markers (IFN-γ, granzyme B, and FasL). CD8+ T cells primarily employed Fas Ligand for cytotoxicity, while CD4+ T cells relied on CD107a. In addition, a statistically significant negative correlation between patient mortality and the presence of CD4+CD107+ pTILs was demonstrated. The engagement with the PD-1/PD-L1 pathway was also more evident in CD4+ and CD8+ pTILs as opposed to TILs. PD-L1 expression in the non-leukocyte fraction of the tumor tissue was relatively lower than in their leukocytic counterparts and upon stimulation, peripheral blood T cells displayed much stronger responses to stimulation than TILs and pTILs. Our results suggest that tumor and peritumoral T cells exhibit limited responsiveness to additional activation signals, while peripheral T cells retain their capacity to respond to stimulatory signals.
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$a Foley, Lily Koumbas $u Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TT, UK
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$a Novak, Vojtech $u Department of Urology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
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$a Taborska, Pavla $u Department of Immunology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
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$a Stakheev, Dmitry $u Department of Immunology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
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$a Rataj, Michal $u Department of Immunology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
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$a Smrz, Daniel $u Department of Immunology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
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$a Fialova, Martina $u Department of Immunology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
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$a Hacek, Jaromir $u Department of Pathology and Molecular Medicine, Second Faculty of Medicine, Charles University, Prague, Czech Republic
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$a Komarc, Martin $u Department of Methodology, Faculty of Physical Education and Sport, Charles University, Prague, Czech Republic
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$a Vesely, Stepan $u Department of Urology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
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$a Babjuk, Marek $u Department of Urology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
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$a Striz, Ilja $u Department of Immunology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
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$a Bartunkova, Jirina $u Department of Immunology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
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$a Buchler, Tomas $u Department of Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
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