CV1-secreting sCAR-T cells potentiate the abscopal effect of microwave ablation in heterogeneous tumors
Microwave ablation (MWA) triggers a weak systemic immune response that leads to the abscopal regression of distant metastases while killing local tumors, known as the abscopal effect. Combining MWA with chimeric antigen receptor (CAR)-T cells demonstrates promise in enhancing the abscopal effect in antigen-homogeneous tumors. However, the loss of the antigen recognized by CAR or intrinsic antigenic heterogeneity in solid tumors poses a major obstacle. SIRPα variant (CV1)-secreting CAR-T (sCAR-T) cells elicit an abscopal effect on distant tumors with antigen heterogeneity in mice receiving local MWA. Mechanistically, sCAR-T cells can locally eliminate antigen-positive tumors and secrete CV1, whereas the secreted CV1 can activate macrophages that migrate to non-ablated tumor sites in response to post-MWA chemokines, eliciting a macrophage-dependent abscopal effect that enables phagocytosis of antigen-heterogeneous cancer cells. This macrophage-dependent abscopal effect instigated by MWA and sCAR-T cells offers a clinically translatable strategy in metastatic solid tumors with antigen heterogeneity.
Authors
- Bihui Cao (ORCID: https://orcid.org/0000-0003-1161-7463)
- Zecong Xiao (ORCID: https://orcid.org/0000-0002-7923-5309)
- Yehuda G. Assaraf (ORCID: https://orcid.org/0000-0001-6692-8221)
- Yubo Zhou
- Xinkun Huang
- Dongliang Leng (ORCID: https://orcid.org/0000-0002-2763-6661)
- Qi Zhao (ORCID: https://orcid.org/0000-0002-5969-6407)
- Manting Liu (ORCID: https://orcid.org/0009-0004-7163-186X)
- Kangshun Zhu (ORCID: https://orcid.org/0000-0001-5142-010X)
- Lu Wang (ORCID: https://orcid.org/0000-0002-6288-8880)
- Zhenfeng Zhang (ORCID: https://orcid.org/0000-0001-5621-9755)
- Qianqian Ni (ORCID: https://orcid.org/0000-0003-4230-5059)
- Wei Cheng (ORCID: https://orcid.org/0009-0003-1225-9140)
- Jia Shen
Institutions
- Indiana University Health (US)
- Sun Yat-sen University (CN)
- National University of Singapore (SG)
- Technion – Israel Institute of Technology (IL)
- University of Macau (MO)
- Second Affiliated Hospital of Guangzhou Medical University (CN)
- Indiana University Bloomington (US)
- Guangdong Academy of Medical Sciences (CN)
- Third Affiliated Hospital of Sun Yat-sen University (CN)
- Indiana University – Purdue University Indianapolis (US)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2025-02-01
- DOI
- https://doi.org/10.1016/j.xcrm.2025.101965
- Citations
- 1
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 1.05
Funders
- United Mitochondrial Disease Foundation
- National Natural Science Foundation of China
- Chinese Academy of Sciences
- Natural Science Foundation of Guangdong Province
- Universidade de Macau
- Fundo para o Desenvolvimento das Ciências e da Tecnologia
- University of Chinese Academy of Sciences
- Guangzhou Municipal Science and Technology Project
- Basic and Applied Basic Research Foundation of Guangdong Province