NEUROIMMUNE INTERACTIONS IN COLORECTAL CANCER: INSIGHTS FROM SINGLE-CELL RNA SEQUENCING ANALYSIS

• Grant number: 25/02768-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2025
• End date: January 31, 2026
• Field of knowledge: Interdisciplinary Subjects
• Principal Investigator: Otávio Cabral Marques
• Grantee: Débora Gomes de Albuquerque Freitas
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/18886-9 - Systemic and integrative analysis of the immune response to Zika and Dengue viral infections, AP.JP

Abstract

Colorectal cancer (CRC) is one of the leading causes of morbidity and mortality worldwide, influenced by genetic, environmental, and immunological factors. Tumor progression is associated with changes in the tumor microenvironment, including extracellular matrix remodeling, immune dysfunction, and alterations in cellular signaling. Additionally, growing evidence suggests that the nervous system can modulate tumor biology by influencing immune responses and promoting a microenvironment favorable to cancer progression. However, the mechanisms underlying this interaction remain incompletely understood.In this study, we performed an integrated single-cell RNA sequencing (scRNA-seq) analysis of multiple CRC datasets to investigate how immune cells express neurotransmitter receptors and how this signaling may be involved in tumor progression. After data curation and integration, we identified distinct cell types within the tumor microenvironment, including myeloid cells, lymphocytes, and endothelial cells. Using differential expression and cell-cell communication analyses, we explored the presence of neuronal receptors in these cell populations and their potential association with inflammatory and immunosuppressive pathways. Furthermore, we examined the relationship between neuropsychiatric disorders, such as chronic stress and depression, and alterations in immune responses in the context of CRC by analyzing transcriptomic data from both brain and tumor tissues. The findings of this study provide new insights into neuroimmune interactions within the tumor microenvironment and may contribute to the development of novel therapeutic approaches aimed at modulating this cellular communication.Keywords: colorectal cancer, tumor microenvironment, neuroimmune interaction, single-cell RNA-seq, neurotransmitters.