Comparative analysis of molecular and cellular mechanisms related to tumour evasion in the triple negative Hs578T breast cancer cell lineage via the PD-1/PDL-1 axis.

• Grant number: 24/01156-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2024
• End date: June 30, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Mari Cleide Sogayar
• Grantee: Maysa Coelho Vieira da Costa
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 16/05311-2 - Regenerative medicine aiming at therapy for chronic degenerative diseases (cancer and diabetes), AP.TEM

Abstract

Breast cancer has a high incidence and lethality in women in Brazil and around the world. More than 73 thousand new cases were estimated for the three-year period 2023 - 2025 in Brazil, placing it as the most common type of cancer in women, regardless of age (excluding non-melanoma skin tumors).The high heterogeneity of breast tumors makes their prediction, diagnosis and prognosis difficult, especially due to the existence of several molecular subtypes and the high complexity of the tumor microenvironment of each subtype.Triple negative breast tumor (TNBC) is the most aggressive subtype of breast cancer, presenting high rates of recurrence and mortality. Due to its molecular profile of low expression of the three main therapeutic targets currently used in the clinic (estrogen and progesterone receptors and HER2), its treatment is highly challenging. The complexity of the interaction between TNBC and its tumor microenvironment is also a clinical challenge, especially considering the ease of establishing tumor evasion mechanisms, via CTLA4 and the PD-1/PDL-1 axis.Recently, research has pointed to non-coding RNAs as excellent targets for studying tumors, considering their relationship with the modulation of processes linked to tumor progression. The long non-coding RNA LINC01133 has great potential in the study of triple-negative breast cancer, and it is important to understand its functioning in non-tumorigenic and tumoral breast tissues, through the search for genes regulated directly or indirectly by this lncRNA and its mechanisms of performance.Thus, the main objective of this project is to investigate, through phenotypic and molecular assays, the possible correlations between LINC01133 and mechanisms of tumor evasion, through comparative analyzes between parental cell lines of triple negative breast tumor (Hs578T) and genetically modified (Hs578T ko lncRNA 01133) under normal conditions and in response to anti-PD-1 and anti-PDL-1 immunotherapeutics via co-culture with the SUP-T1 lymphoblastic cell line.