CD47 Blockade Triggers T Cell-mediated Destruction of Immunogenic Tumors

Overview

Journal Nat Med

Specialties General Medicine
Molecular Biology

Date 2015 Sep 1

PMID 26322579

Citations 389

Authors

Xiaojuan Liu

Yang Pu

Kyle Cron

Liufu Deng

Justin Kline

William A Frazier

Hairong Xu

Hua Peng

Yang-Xin Fu

Meng Michelle Xu

Affiliations

Soon will be listed here.

Abstract

Macrophage phagocytosis of tumor cells mediated by CD47-specific blocking antibodies has been proposed to be the major effector mechanism in xenograft models. Here, using syngeneic immunocompetent mouse tumor models, we reveal that the therapeutic effects of CD47 blockade depend on dendritic cell but not macrophage cross-priming of T cell responses. The therapeutic effects of anti-CD47 antibody therapy were abrogated in T cell-deficient mice. In addition, the antitumor effects of CD47 blockade required expression of the cytosolic DNA sensor STING, but neither MyD88 nor TRIF, in CD11c+ cells, suggesting that cytosolic sensing of DNA from tumor cells is enhanced by anti-CD47 treatment, further bridging the innate and adaptive responses. Notably, the timing of administration of standard chemotherapy markedly impacted the induction of antitumor T cell responses by CD47 blockade. Together, our findings indicate that CD47 blockade drives T cell-mediated elimination of immunogenic tumors.

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