Association between GALR2 and efferocytosis markers with presence of Tertiary Lymphoid Structures (TLS) and immune response profile in OSCC patients: interaction between immunosuppressive biological aspects and tumor aggressiveness

• Grant number: 22/11191-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): September 01, 2022
• Effective date (End): August 31, 2025
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Eny Maria Goloni Bertollo
• Grantee: Vitória Scavacini Possebon
• Host Institution: Faculdade de Medicina de São José do Rio Preto (FAMERP). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São José do Rio Preto , SP, Brazil
• Associated research grant: 20/00394-2 - Head and neck squamous cell carcinoma (HNSCC) invasion and distant metastasis: relevance and crosstalk between GALR2 and efferocytosis in the tumor microenvironment and hematogenic dissemination, AP.TEM

Abstract

Among the reported cases of head and neck cancer, Head and Neck Squamous Cell Carcinoma (HNSCC) is responsible for approximately 90%, being a disease with a high mortality rate and poor prognosis. Oral Squamous Cell Carcinoma (OSCC), usually diagnosed at an advanced stage, has a high frequency of recurrence and metastasis and a 5-year survival rate of about 50%. Morbidity and mortality associated with these tumors is related to the extent of locoregional invasion and the occurrence of nodal and distant metastasis. In the last 2 decades, the co-option/reactivation of the antitumor immune response has been intensively investigated as a therapeutic approach with significant impacts on the survival of OSCC patients, but these positive effects of these new therapies are limited to a small proportion of the cases. Thus, more recently, several studies have focused on understanding the immune response in the tumor microenvironment, seeking to identify characteristics or biomarkers that indicate the potential for response to immunotherapies. In this sense, the thematic project (2020/00394-2) to which this project is linked investigates the influence of two biological aspects, I) GALR2 expression/activity and II) efferocytosis activity, which due to their immunosuppressive nature may represent obstacles to the reactivation/cooptation of the antitumor immune response. More than the simple presence of different leukocytes in the stroma and in the tumor mass itself, the spatial organization of these cells in the Tumor Microenvironment (TME) in Tertiary Lymphoid Structures (TLS), including B, dendritic and follicular T cells in structures with different levels of structural maturation (follicular zone, germinal center) and similar to secondary lymphoid structures has been described as an important aspect in the antitumor immune response and effectiveness of immunotherapies in several types of solid tumors, including HNSCC. The presence of these TLS, their level of structural maturation and the phenotypic subtype of the leukocytes present is considered relevant in the pattern of response to immunotherapies and may be an important biomarker in the prognosis and therapeutic management in HNSCC. The possible influence/interaction of immunosuppressive biological aspects focused on by the thematic process (GALR2 expression/activity, efferocytosis activity) with the presence of TLS in the primary tumor and the pattern of systemic immune response of patients with OSCC is not known and may provide prognostic biomarkers of antitumor response and responsiveness to immunotherapy. (AU)