Dados do Resumo

Título

Modulation of T Cell Function by Cancer Therapy VEGFR Tyrosine Kinase Inhibitors

Introdução

Tyrosine kinase inhibitors (TKIs) are widely used in the treatment of various cancers by targeting and disrupting specific signaling pathways in tumor cells. More recently, immune checkpoint blockade (ICB) immunotherapy has been introduced, aiming to restore T cell activation and enhance the anti-cancer immune response. While the literature indicates that VEGFR pathways are also present in immune cells, the effects of TKIs on these cells remain poorly understood.

Objetivo

Our aim was to investigate the role of TKIs in T cells and their impact on immune checkpoint receptors.

Métodos

We isolated T cells from 17 healthy volunteers. Gene expression was analyzed via qPCR, signaling pathways were assessed using Western Blotting, and T cell proliferation was evaluated through CFSE/FACS. Additionally, in silico analysis was performed using TCGA data from lung cancer patients.

Resultados

Activated lymphocytes expressed VEGFR. Public data analysis revealed the expression of receptor tyrosine kinases (RTKs) in leukocytes, including T cell subtypes in tumors and lymph nodes. Treatment with TKIs modulated the signaling pathways in lymphocytes, particularly at higher inhibitor concentrations. Both CD4+ and CD8+ T cells exhibited reduced proliferation, with notable changes in their proliferative patterns post-TKI treatment. Additionally, TKI treatment slightly affected immune checkpoint regulation.

Conclusões

Our findings show that RTKs are expressed in lymphocytes, with their signaling pathways being altered by TKI treatment. TKIs negatively regulated the proliferation of CD4+ and CD8+ T lymphocytes, particularly at high concentrations. This study highlights the potential for TKIs to impact immune cells and suggests that these effects may be concentration-dependent, emphasizing the need for careful consideration in combined cancer therapies.

Palavras Chave

T Lymphocytes; Renal Cancer; targeted therapy