Research ArticleCANCER IMMUNOLOGY

KIR3DL3-HHLA2 is a human immunosuppressive pathway and a therapeutic target

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Science Immunology  09 Jul 2021:
Vol. 6, Issue 61, eabf9792
DOI: 10.1126/sciimmunol.abf9792

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KIR3DL3-HHLA2 interactions protect tumors

HHLA2 (a B7 family member) has both immune inhibitory and activating abilities and is expressed in many human cancers. These differing functions rely on the receptor to which it binds, yet many of these receptors are uncharacterized. Here, Wei et al. found that KIR3DL3 bound to HHLA2 and was expressed on effector memory CD8+ T cells and CD56dim NK cells. Interactions of KIR3DL3 with tumoral HHLA2 inhibited the function and killing capacity of both CD8+ T cells and NK cells. KIR3DL3+ immune cells infiltrated various types of HHLA2+ tumors from patients with cancer, and blockade of KIR3DL3 inhibited the growth of tumors in various mouse models. Thus, KIR3DL3-HHLA2 inhibits immune-mediated clearance of tumor cells and presents a possible immunotherapeutic target for cancer.

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