Characterization of Vδ2+ γδ T cell populations in breast cancers

The rationale for therapeutic targeting of Vδ2+ γδ T cells in breast cancer is strongly supported by in vitro and murine preclinical investigations, characterizing them as potent breast tumor cell killers and source of Th1-related cytokines, backing cytotoxic αβ T cells. Nonetheless, insights regarding Vδ2+ T cell phenotypic alterations in human breast cancers are still lacking. This paucity of information is partly due to challenging scarcity of these cells in surgical specimens. αβ T cell phenotypic alterations occurring in the tumor bed are detectable in periphery and correlate with adverse clinical outcome. Thus, we sought to determine whether Vδ2+ T cells phenotypic changes can be detected within breast cancer patients’ peripheral blood, along with association with tumor progression. By using mass cytometry, we quantified 130 immune variables from untreated breast cancer patients’ peripheral blood. Supervised analyses and dimensionality reduction algorithms evidenced circulating Vδ2+ T cell phenotypic alterations already established at diagnosis. Foremost, terminally differentiated Vδ2+ T cells displaying phenotypes of exhausted senescent T cell associated with lymph node involvement. Thereby, our results support Vδ2+ T cells implication in breast cancer pathogenesis and progression, besides shedding light on liquid biopsies to monitor surrogate markers of tumor-infiltrating Vδ2+ T cell anti-tumor activity.