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IL-36γ Armored CAR T Cells Reprogram Neutrophils to Induce Endogenous Antitumor Immunity

GSE306905 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2025/12/31 Platform GPL24247
Summary
Chimeric antigen receptor (CAR) T cells are ineffective against solid tumors due to obstacles of antigen heterogeneity and the immunosuppressive tumor microenvironment (TME). Previous efforts focused on enhancing cytotoxicity and persistence of CAR T cells, while the feasibility of improving their therapeutic efficacy by leveraging the modulatory effects of CAR T cells on host anti-tumor immunity remains unclear. Here, we report that IL-36γ armored CAR T cells eradicated primary solid tumors and enabled rejection of rechallenged antigen-negative tumors. IL-36γ armored CAR T cells favorably modulated the TME and reprogrammed unique neutrophil subsets with tumoricidal ability and antigen-(cross)presenting functions, resulting in the induction of endogenous T cells recognizing tumor antigens beyond CAR-targeted antigens. Our study demonstrates that neutrophil engagement by CAR T cells is a critical step in the establishment of the cancer-immunity cycle and introduces a broadly applicable method to overcome key barriers to adoptive cell therapies for solid tumors.
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Direct links to NCBI, no account and no request form: the whole study as GSE306905_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 6 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1313888 and SRA study SRP616610. Searching any of these in the dataset finder brings you back here.

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