SynNotch-iNOS CAR-macrophages remodel the tumor immune microenvironment and exhibit antitumor efficacy via a CD4+ T cell-dependent mechanism

Yuling Hong

doi:10.1016/j.trsl.2026.06.017

SynNotch-iNOS CAR-macrophages remodel the tumor immune microenvironment and exhibit antitumor efficacy via a CD4+ T cell-dependent mechanism

2026-06-24

0

PRE

AI

Y

Yuling Hong

Z

Zhenqiong Zhou

C

Cixin Liang

L

Linying Li

Q

Qingxiang Gao

J

JZ Jie Zhang

S

Shih‐Chin Cheng *

DOI：10.1016/j.trsl.2026.06.017

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• Engineered synNotch-iNOS CAR-M enables antigen-triggered nitric oxide release. • CAR iNOS-M remodels the tumor immune microenvironment to inhibit solid tumors. • Antitumor efficacy is strictly dependent on CD4+ T cells but independent of CD8+ T cells. • CAR iNOS-M treatment reduces lung interstitial macrophages and PF4 levels. • Disruption of PF4 signaling inhibits Th1-Treg polarization and T-cell exhaustion.

SynNotch-iNOS CAR-macrophages remodel the tumor immune microenvironment and exhibit antitumor efficacy via a CD4+ T cell-dependent mechanism

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