Contribution of cells with suppressor function in the susceptibility to lung cancer promoted by previous gastrointestinal infection

• Grant number: 25/13199-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2025
• End date: August 31, 2026
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Denise Morais da Fonseca
• Grantee: Marcos Paulo Santos Coelho
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 21/06881-5 - Gut-lung axis: understanding the immune dialogue between barrier tissues in the development of disease, AP.JP2

Abstract

Gastrointestinal pathogens represent one of the most common types of infections worldwide. Numerous studies have been conducted to understand the impact of these infections on intestinal mucosal homeostasis and their long-term consequences for the host. The Mucosal Immunology Laboratory has described that even after the resolution of certain acute infectious episodes, such as in the case of the bacterium Yersinia pseudotuberculosis (YP), there is a change in immune tone and lymphatic remodeling in the intestine and mesentery, resulting in chronic inflammation and preventing the development of canonical intestinal responses. This change in immune tone is not restricted to the intestinal mucosa and also impacts the pulmonary mucosa. Preliminary results indicate that this inflammatory environment is associated with failure of regulatory T cells (Tregs) and a consequent increase in susceptibility to inflammatory bowel disease (IBD). However, the increase in immunovigilance resulting from Treg failure led to protection against the development of tumors in the intestinal mucosa, which then established themselves in the pulmonary mucosa of the animals. These animals also show more tumor development when it is primarily induced in the lungs, suggesting a change in the pulmonary microenvironment mediated by the gut-lung axis. This axis is one of immunological communication between organs, occurring via inflammatory mediators, cell trafficking, or components/metabolites of the commensal microbiota. We hypothesize that functional changes in the gut-lung axis after infection could exclude the establishment of cells with regulatory/suppressive function in the intestinal mucosa and divert them to the lung, differentially influencing the establishment of intestinal and lung cancer after infection. In this project, we will evaluate the suppressive capacity of lymphoid and myeloid cells isolated from the lung parenchyma after control of YP infection and their contribution to increased susceptibility to the development of neoplasms in the lung mucosa. The results obtained in this project will allow us to understand the mechanisms involved in differential susceptibility to the development of post-infection lung and intestinal cancer, as well as the overall immunological relationship between the two organs, contributing to a better understanding of the gut-lung axis.