ROLE OF ADRENERGIC SIGNALING IN INNATE LYMPHOID CELLS OF CANCER PATIENTS

• Grant number: 24/08864-9
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: February 01, 2025
• End date: January 31, 2026
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: Patricia Chakur Brum
• Grantee: Janaina da Silva Vieira
• Supervisor: Jandus Camilla
• Host Institution: Escola de Educação Física e Esporte (EEFE). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Université de Genève, Switzerland
• Associated to the scholarship: 21/11800-4 - Dysautonomia and immunosuppression in Cancer: effect of aerobic exercise training, BP.DR

Abstract

Recent advances in cancer immunotherapy have highlighted the crucial role of the immune system in fighting tumors, with T cell-targeted therapies showing significant success. However, only a subset of patients benefits from these therapies, indicating the need to understand other immune components within the tumor microenvironment. Innate lymphoid cells (ILCs), can play key roles in immune surveillance and tissue homeostasis, have emerged as important regulators in cancer. ILCs can exert both pro- and anti-tumor effects depending on their context, thereby influencing tumor dynamics. This project explores the roles of ILCs, with focus on natural killer (NK) cells, particularly their interaction with the sympathetic nervous system (SNS) and adrenergic signaling pathways. The SNS, through adrenergic signaling, has been implicated in cancer progression, partially mediated by immunosuppression. Beta-adrenergic receptors (²-ARs), especially the ²2 subtype, are highly expressed in immune cells and play critical roles in cellular responses. Canonical and non-canonical pathways can lead to different and sometimes opposite cell functions. These pathways impact immune cell function and gene transcription, and might be involved in cancer progression. The role of adrenergic signaling in NK cells, remains underexplored. This proposal aims to elucidate whether adrenergic signaling pathways affects ILC functions in the tumor microenvironment, focusing on NK cells. By investigating alterations in these pathways in cancer patients, we aim to determine their impact on antitumor responses and contribute to the development of therapeutic strategies to modulate adrenergic signaling for enhanced NK cell-mediated antitumor immunity.