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

Martina Borcinova ¹, Robin Bartolini ², Lily Koumbas Foley ³

¹Gynecologic Oncology Centre, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic.
²Lausanne Center for Immuno-oncology Toxicities (LCIT), Service of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
³Chemokine Research Group, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TT, UK.
⁴Department of Urology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
⁵Department of Immunology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
⁶Department of Immunology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
⁷Department of Pathology and Molecular Medicine, Second Faculty of Medicine, Charles University, Prague, Czech Republic.
⁸Department of Methodology, Faculty of Physical Education and Sport, Charles University, Prague, Czech Republic.
⁹Department of Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.

⁰Gynecologic Oncology Centre, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic.

Translational Oncology +

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February 4, 2024

View abstract on PubMed

Summary

Tumor-infiltrating lymphocytes in renal cell carcinoma (RCC) show high cytokine production but limited responsiveness. Peritumoral T cells correlate with better survival, suggesting distinct roles in the tumor immune microenvironment (TIME).

Area Of Science

Immunology
Oncology
Renal Cell Carcinoma Research

Background

Renal cell carcinoma (RCC) is often diagnosed at a metastatic stage.
Understanding the tumor immune microenvironment (TIME) is crucial for RCC treatment.
Immune cell function within the tumor and surrounding tissues requires detailed characterization.

Purpose Of The Study

To comprehensively analyze the tumor immune microenvironment (TIME) in RCC patients.
To characterize phenotypic and functional patterns of immune cells, particularly T cells.
To evaluate T cell activation status and migratory potential in different tissue compartments.

Main Methods

Flow cytometry and Luminex analyses were used to assess T cells.
T cells were analyzed from peripheral blood, tumor, peritumoral, and healthy renal tissues.
Analyses were performed before and after T cell-specific stimulation.

Main Results

Tumor-infiltrating lymphocytes (TILs) produced more cytokines (IFN-γ, granzyme B, FasL) than peritumoral T cells (pTILs).
CD8+ T cells used Fas Ligand, while CD4+ T cells used CD107a for cytotoxicity.
Higher CD4+CD107+ pTILs correlated with decreased patient mortality; PD-1/PD-L1 engagement was higher in pTILs than TILs.
Peripheral blood T cells showed stronger responses to stimulation than TILs and pTILs, indicating limited responsiveness of tumor-associated T cells.

Conclusions

TILs and pTILs have heightened cytokine production but limited responsiveness to further activation.
CD4+CD107+ pTILs are associated with improved patient survival in RCC.
Peripheral T cells retain greater activation capacity compared to T cells within the tumor microenvironment.

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