Molecular Features of T Lymphocytes in the Immune Response Against Breast Cancer

Losurdo, Agnese (2021). Molecular Features of T Lymphocytes in the Immune Response Against Breast Cancer. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.00012511

Abstract

Luminal-like breast cancer (BC) constitutes the majority of BC subtypes, but, differently from highly aggressive triple negative breast cancer (TNBC), is poorly infiltrated by the immune system. The quality of the immune infiltrate in luminal-like BCs has been poorly studied, thus a biological basis for the further investigation of immunotherapeutic strategies is missing. In this thesis, we used high-dimensional single-cell technologies to characterize the T cell populations infiltrating luminal-like tumors, and we identified heterogeneous behavior within the tissue-resident memory CD8+ T (Trm) cells. We defined that a subset of CD127-CD39hi Trm cells is preferentially present in the tumor compared to the adjacent normal breast tissue or peripheral blood, displayed enhanced effector functions compared to the CD127+ CD39lo Trm counterpart, and was specifically associated with positive prognosis. Nevertheless, the prognostic benefit was lost in the presence of highly-suppressive CCR8hi ICOShi IRF4+ effector Tregs. Our results suggest that combinatorial strategies aiming at boosting Trm function while relieving from Treg-mediated immunosuppression are needed to achieve proper tumor control in luminal-like BCs.

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