Modulation of the expression of programmed cell death ligand 1 (PD-L1) inhibitors by toll-like receptors and cytokines associated with BCG vaccination.

• Grant number: 23/15470-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2024
• End date: December 31, 2024
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Leonardo Oliveira Reis
• Grantee: Maria Carolina Ximenes de Godoy
• Host Institution: Escola de Ciências da Vida (ECV). Pontifícia Universidade Católica de Campinas (PUC-CAMP). Campinas , SP, Brazil

Abstract

Immune checkpoint inhibitors have revolutionized cancer therapy. With this development, programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have been important in understanding how cancer cells evade the immune system. Bacillus Calmette-Guérin (BCG) is currently used as the gold standard adjuvant treatment for non-muscle-invasive bladder cancer. BCG stimulates Toll-like receptors (TLR) and TLRs have immunotherapeutic potential by stimulating the immune response. However, BCG appears to increase PD-L1 expression and greater efficacy was obtained when it was co-administered with an anti-PD-L1 antibody in an experimental mouse cancer model. Other TLR ligands could also modify the expression of PD-L1 on tumor cells, and cytokines secreted by T cells can alter the production of PD-L1. In mice, vaccination with BCG increased the production of IFN-g, considered the main cytokine in the positive modulation of PDL1. In healthy human volunteers, vaccination increased the production of cytokines such as interleukin (IL)-1 ² and tumor necrosis factor (TNF)-±. Thus, the objective of this work is to study the response induced by BCG and other TLR ligands on the expression of PD-L1, as well as a possible modulating activity of this expression by the cytokines produced by BCG vaccination in humans through MCF- cell culture. 7 and MDA-MB-231, cells that produce large amounts of PD-L1 as an in vitro model.