Analysis of the tumor-antigen specific T cell repertoire in healthy donors using T cell libraries

• Grant number: 16/01137-8
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: September 01, 2016
• End date: November 30, 2016
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Jose Alexandre Marzagão Barbuto
• Grantee: Mariana Pereira Pinho
• Supervisor: Federica Sallusto
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Università della Svizzera italiana, Switzerland
• Associated to the scholarship: 14/25988-1 - Analysis of the T cell repertoire in cancer patients: unveiling the antitumor immune response in humans, BP.DR

Abstract

It is well known that, sometimes, the adaptive immune response is able to specifically recognize and eliminate tumor cells, a characteristic that has been exploited in the development of immunotherapeutic protocols. This is only possible because, during the tumorigenesis, transformed cells accumulate changes in protein sequence (mutations) and expression pattern, generating tumor-associated antigens (TAAs) that can be recognized and, thus, induce adaptive immune responses. However, TAAs, due to their similarity and even identity to self-antigens, should have caused the elimination, by central tolerance mechanisms, of T cells bearing high affinity receptors to them. Nevertheless, TAA-specific T cells can be detected in cancer patients and also in healthy individuals, but their broad specificity patterns and frequency are unknown. This happens because, usually, this kind of analysis is performed by evaluating the presence of T cells specific for one epitope of one TAA. Yet, the improvement of active immunotherapy protocols for cancer depends on the determination of the real potential for recognition of TAAs by the immune system. Therefore, this project aims to study in deep the repertoire of TAAs-specific T lymphocytes in healthy donors. For this, the TAA-specific T lymphocyte repertoire will be assessed by a novel methodology that permits a broad evaluation of the antigen-specific T cell repertoire: the screening of T cell libraries. These libraries will be constructed by unspecific expansion of blood T cells from each of the known T cell subpopulations (naïve/central memory/effector memory or Th1/Th2/Th17/Th22) and will be screened with different TAAs. With this methodology, we hope to better understand the real potential of the human immune system to respond to tumor antigens.

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)

PATENTE, THIAGO A.; PINHO, MARIANA P.; OLIVEIRA, ALINE A.; EVANGELISTA, GABRIELA C. M.; BERGAMI-SANTOS, PATRICIA C.; BARBUTO, JOSE A. M.. Human Dendritic Cells: Their Heterogeneity and Clinical Application Potential in Cancer Immunotherapy. FRONTIERS IN IMMUNOLOGY, v. 9, JAN 21 2019. (14/25988-1, 16/01137-8, 14/26437-9)

PINHO, MARIANA PEREIRA; PATENTE, THIAGO ANDRADE; FLATOW, ELIZABETH ALEXANDRA; SALLUSTO, FEDERICA; MARZAGAO BARBUTO, JOSE ALEXANDRE. Frequency determination of breast tumor-reactive CD4 and CD8 T cells in humans: unveiling the antitumor immune response. ONCOIMMUNOLOGY, v. 8, n. 8, MAY 2019. (14/25988-1, 16/01137-8)

PINHO, MARIANA P.; LEPSKI, GUILHERME A.; REHDER, ROBERTA; CHAUCA-TORRES, NADIA E.; EVANGELISTA, GABRIELA C. M.; TEIXEIRA, SARAH F.; FLATOW, ELIZABETH A.; DE OLIVEIRA, JAQUELINE V.; FOGOLIN, CARLA S.; PERES, NATALY; et al. Near-Complete Remission of Glioblastoma in a Patient Treated with an Allogenic Dendritic Cell-Based Vaccine: The Role of Tumor-Specific CD4+T-Cell Cytokine Secretion Pattern in Predicting Response and Recurrence. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 10, p. 10-pg., 2022-05-01. (14/25988-1, 16/01137-8)