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The role of T follicular helper cells in the immune response to breast cancer

par Langouo Fontsa, Mireille
Président du jury Corazza, Francis
Promoteur Goriely, Stanislas
Publication Non publié, 2022-11-08

Thèse de doctorat

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• Statistiques

Résumé :

In breast cancer (BC), tumor-infiltrating lymphocytes (TIL) can organize in tertiary lymphoid structures (TLS) in the stroma. We show that CXCL13, a B-cell chemoattractant produced principally by both chronically differentiated CXCR5-PD-1hiICOSint CD4+ and CD8+ TIL, is involved in TLS formation and associated with favorable clinical outcomes. The present study investigated how TLS functionally contributes to immune responses in BC. CXCR5, the CXCL13 receptor, is expressed on infiltrating B-cells, CD4+ T-cells [follicular helper (Tfh) or regulatory (Tfr) T cells], and interestingly a CD8+ T-cell subpopulation. All of the CXCR5+ TIL co-localize in TLS where the balance between functional PD-1hiICOSint Tfh TIL and functional GARP+ Tfr TIL dictate B cells differentiation and cytotoxic immune response with respectively Ig production in germinal center and cytotoxic cells revitalization with granzyme B production and PD-1 decrease. TLS is an essential key for anti-tumoral immune response and may be considered as a new target for immunotherapy.