Identification of infiltrating subsets of T regulatory cells in head and neck squamous cell carcinomas (HNSCC): crosstalk with macrophages and GALR2

• Grant number: 24/13134-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: February 28, 2025
• End date: February 27, 2026
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Carlos Rossa Junior
• Grantee: Milena Moraes de Carvalho
• Supervisor: Kjetil Tasken
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Institution abroad: University of Oslo (UiO), Norway
• Associated to the scholarship: 22/01484-0 - Influence of Tregs on the phenotype of monocytes/macrophages in the tumor microenvironment and on response of Oral Squamous Cell Carcinoma to cytotoxic chemotherapy, BP.DR

Abstract

The interaction between the immune system and cancer is complex, as the immune response may be construed either as pro- or anti-tumoral, depending on the type and stage of the neoplasia. Comprehension of the immune response's role in the tumorigenesis and progression of head and neck squamous cell carcinomas (HNSCC) is still incomplete; nevertheless, activation and/or rescuing of the immune response have been actively investigated as a therapeutic approach based on the concept that an immunosuppressive tumor microenvironment in this cancer is conducive to tumor growth and loco-regional dissemination. T regulatory cells (Tregs) are generally considered the prototypical negative regulators of the immune response and thus may have a central role in the tumor immunosuppressive landscape; however, there is controversial information on the association between Treg infiltration in HNSCC and prognosis/outcome. Distinct subsets of Tregs have been identified in some types of cancer, but there is no information on the prevalence of these Treg subsets in HNSCC or on their association with tumor aggressiveness and outcome. We hypothesize that macrophages, as the most abundant immune cell type in the tumor microenvironment and strongly associated with prognosis/outcome of HNSCC/OSCC, have reciprocal interactions with Tregs that are spatially-restricted. Increased GALR2 expression is described as a significant characteristic in the immunosuppressive gene signature in HNSCC and we have shown the suppressive effects of Galanin/GALR2 axis in immune cells in vitro. The proposed experiments will investigate the crosstalk among GALR2, macrophages and different Treg subsets in HNSCC patient-derived samples. Using in vivo samples, we will study the influence of Tregs on early and late OSCC progression, as well as on macrophage phenotype and CD8+ T cell activation. Imaging mass cytometry is the proposed approach because it allows for multiplexed analyses of target proteins while still retaining information about spatial distribution in the tumor microenvironment. The results of the proposed experiments will complement and expand the findings of the research projects (PhD stipend and research grant awards) associated with this application.