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Chimeric antigen receptor‐modified macrophages trigger systemic anti‐tumour immunity
Author(s) -
Niu Zhiyuan,
Chen Guanxu,
Chang Wei,
Sun Pengyang,
Luo Zhixia,
Zhang Huiyong,
Zhi Lingtong,
Guo Changjiang,
Chen Han,
Yin Meichen,
Zhu Wuling
Publication year - 2021
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.5585
Subject(s) - biology , immune system , spleen , immunology , cancer research , population , cd19 , medicine , environmental health
Preliminary results and emerging data have shown that lipid droplet high (LD hi ) immunosuppressive cells accumulate in tumour tissues. By tracking and phenotypic profiling of LD hi cells, we find that LD hi CD19 + , LD hi CD11b + , and LD hi Ly6G + immune cell populations appear in the spleen, thymus, and tumour tissues in a syngeneic tumour model. Using a contact‐dependent reporter system, we discover a LD hi CCR7 hi immunosuppressive cell population that migrates from tumour tissues to the spleen and thymus. Hence, we engineered a family of chimeric antigen receptor‐modified macrophages (CAR‐Ms) that direct macrophages to CCR7‐positive cells and show that the cytosolic domain from Mer receptor tyrosine kinase (MerTK) triggers tumour cell cytotoxicity by the CAR‐Ms. In vivo , CCR7‐targeted CAR‐Ms suppressed tumour growth and prolonged survival by preventing metastasis and by inducing systemic anti‐tumour immunity through retarding the migration of LD hi CCR7 hi immunosuppressive cells from tumour tissues to distal immune organs, indicating an important role for CCR7 in tumour cell‐induced immune tolerance. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.