Evaluation of the Role of the TK1 Gene in Malignancy and Immune Evasion of Adrenocortical Tumors in vitro and in vivo model

• Grant number: 23/11490-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2025
• Status: Discontinued
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Carlos Alberto Scrideli
• Grantee: Alcides Euzebio Tavares Xavier
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 25/14697-0 - Immune evasion and resistance to immunotherapy in TK1-High Adrenocortical Tumors: evaluation in novel in vivo and in vitro models., BE.EP.DR

Abstract

Adrenocortical tumor (ACT) is a rare neoplasm with a poor prognosis in advanced cases. These tumors exhibit high heterogeneity, and the anatomopathological parameters used, especially in pediatric cases, are considered imprecise. So far, it has not been possible to establish a well-defined prognostic correlation, which results in difficulties in determining disease progression and guiding treatment. Complete surgical resection is the only therapeutic option with curative potential. Due to the scarcity of information about the biology of ACTs and study models that mimic this tumor, especially in pediatric cases, understanding the molecular and immunological mechanisms of initiation/development and progression of these tumors remains a challenge. Our preliminary results, in collaboration with a researcher from Harvard Medical School, using public data from adult patients (TCGA), pediatric patients (GSE76019), and tumors from a transgenic adrenocortical carcinoma model (data provided by a collaborator, not publicly available), show that the TK1 gene is upregulated in ACT cases with worse prognosis, as well as in murine tumors. Moreover, TK1 expression is correlated with the gene expression of Cyclin B1 and Cyclin B2, known cell cycle markers. The activity of the protein transcribed by TK1 is intrinsically linked to the process of DNA synthesis and repair, peaking in the S phase. Additionally, TK1 expression correlates with the infiltration of immune cells such as CD4+ T cells, CD4+ Th2 T cells, and MDSCs in ACT. Thus, this project aims to evaluate the TK1 gene as a biomarker and its functional relevance in both in vitro and in vivo models, in order to characterize and explore its molecular and immunological implications in tumor progression mechanisms. We hope to provide new insights for the prognosis, diagnosis, and clinical management of this disease.