Human CD26<sup>high</sup> T cells elicit tumor immunity against multiple malignancies via enhanced migration and persistence.

Bailey, Stefanie R; Nelson, Michelle H; Majchrzak, Kinga; Bowers, Jacob S; Wyatt, Megan M; Smith, Aubrey S; Neal, Lillian R; Shirai, Keisuke et al. · Nat Commun · 2017

basic_science · Level V

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Abstract

CD8+ T lymphocytes mediate potent immune responses against tumor, but the role of human CD4+ T cell subsets in cancer immunotherapy remains ill-defined. Herein, we exhibit that CD26 identifies three T helper subsets with distinct immunological properties in both healthy individuals and cancer patients. Although CD26neg T cells possess a regulatory phenotype, CD26int T cells are mainly naive and CD26high T cells appear terminally differentiated and exhausted. Paradoxically, CD26high T cells persist in and regress multiple solid tumors following adoptive cell transfer. Further analysis revealed that CD26high cells have a rich chemokine receptor profile (including CCR2 and CCR5), profound cytotoxicity (Granzyme B and CD107A), resistance to apoptosis (c-KIT and Bcl2), and enhanced stemness (β-catenin and Lef1). These properties license CD26high T cells with a natural capacity to traffic to, regress and survive in solid tumors. Collectively, these findings identify CD4+ T cell subsets with properties critical for improving cancer immunotherapy.

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