Cellular Immune Responses in Triple-negative Breast Cancer - High Throughput Immunogenetic Studies

Triple Negative Breast Cancer

T cells, Tumor-infiltrating lymphocytes, Next-generation sequencing, T cell receptor, Spatial transcriptomics, Neoepitopes, TR beta chain, TRb clonotypes, TRb gene repertoire, Cellular immunity

This project introduces a novel methodology for the in-depth immunogenetic characterization of the TR gene repertoire in solid tumors, holding the promise to offer unprecedented insights into the TR anti-tumor specificity and the prognostic/predictive value of TR gene repertoire signatures.

The goal of this observational study is to address the role of T cells in the tumor microenvironment of TNBC. In detail, this study aims to: (i) explore the immunogenetic characteristics of the TR gene repertoire as informative prognostic/predictive biomarkers in TNBC (ii) identify immunogenic neoepitopes arising from common tumor-specific non-synonymous gene mutations, as well as the corresponding neoepitope-specific T cells (iii) describe, in single-cell resolution, the spatial organization of the intricate crosstalk between tumor cells and neoepitope specific-T cells, and (iv) delineate the functional properties of T cells within the TME. All the experimental results, regarding the TR repertoire features and the spatial organization of the TME, will be correlated with clinical outcome measurements (e.g. overall survival, progression time), which are available from the detailed patients medical record.

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