Evaluation of soluble PD-L1 in combination with its protein expression in circulating tumor cells and other soluble factors as serum markers of treatment response in patients with Non-Metastatic Triple Negative Breast Cancer

• Grant number: 22/15151-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2023
• End date: June 30, 2027
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Ludmilla Thomé Domingos Chinen
• Grantee: Jacqueline Aparecida Torres
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Immunotherapy has provided beneficial results for cancer patients. Recently, the ANVISA, based on the KEYNOTE-355 study, approved the use of the immune checkpoint inhibitor (ICI) pembrolizumab plus chemotherapy for patients with unresectable locally recurrent or metastatic triple-negative breast cancer, with PD-L1 expression e 10. Although the results are encouraging, evidence suggests that only a fraction of patients benefit from treatment and may have serious immune-related adverse events. To minimize reactions to ICIs, it is importante to establish predictive biomarkes of response, and blood biomarkes are na option due to non-invasive nature. Laboratory values such a neutrophils-lymphocytes ratio (NLR), the presence of soluble PD-L1 (sPD-L1), of secreted cytokines (TGF-², IL-8) and PD-L1 expression in circulating tumor cells are potential predictive biomarkers. Objective: To verify if the sequential analysis of sPD-L1, PD-L1 expressed in CTCs, soluble TGF-² and IL-8 and NLR can be predictive factors for patients with TNBC stages I-III; to verify if there is a relationship between sPD-L1, PD-L1 expressed in CTCs, soluble TGF-² and IL-8 and NLR and invasive disease-free survival in stage I-III patients. Methodology: we will collect blood samples at 2 times (T1: before treatment at the clinician's choice) (T2: 6 months after treatment) 10mL peripheral blood in EDTA tubes to CTCs enrichment using the ISET methodology and 2mL blood for analysis of sérum biomarkers (sPD-L1, TGF-² e IL-8) by ELISA assay. We will calculate the NLR based on medical record data and we will do immunocytochemical assay for PD-L1 on CTCs. In this way, we hope to contribute to the personalization of the treatment of patients with TNBC in early stages. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CHINEN, LUDMILLA THOME DOMINGOS; TORRES, JACQUELINE APARECIDA; CALSAVARA, VINICIUS FERNANDO; BRITO, ANGELO BORSARELLI CARVALHO; SILVA, VIRGILIO SOUSA E; NOVELLO, ROBERTO GABRIEL SANTIAGO; FERNANDES, THAISSA CARVALHO; DECINA, ALESSANDRA; DACHEZ, ROGER; PATERLINI-BRECHOT, PATRIZIA. Circulating Polyploid Giant Cancer Cells, a Potential Prognostic Marker in Patients with Carcinoma. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 25, n. 18, p. 15-pg., 2024-09-01. (22/15151-3)