| First Author | Bian Z | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 3229 |
| PubMed ID | 34050181 | Mgi Jnum | J:331120 |
| Mgi Id | MGI:6713991 | Doi | 10.1038/s41467-021-23442-z |
| Citation | Bian Z, et al. (2021) Intratumoral SIRPalpha-deficient macrophages activate tumor antigen-specific cytotoxic T cells under radiotherapy. Nat Commun 12(1):3229 |
| abstractText | Radiotherapy (RT)-induced tumoricidal immunity is severely limited when tumors are well-established. Here, we report that depleting SIRPalpha on intratumoral macrophages augments efficacy of RT to eliminate otherwise large, treatment-resistant colorectal (MC38) and pancreatic (Pan02 and KPC) tumors, inducing complete abscopal remission and long-lasting humoral and cellular immunity that prevent recurrence. SIRPalpha(-deficient) macrophages activated by irradiated tumor-released DAMPs exhibit robust efficacy and orchestrate an anti-tumor response that controls late-stage tumors. Upon RT-mediated activation, intratumoral SIRPalpha(-deficient) macrophages acquire potent proinflammatory features and conduct immunogenic antigen presentation that confer a tumoricidal microenvironment highly infiltrated by tumor-specific cytotoxic T cells, NK cells and inflammatory neutrophils, but with limited immunosuppressive regulatory T cells, myeloid derived suppressor cells and post-radiation wound-healing. The results demonstrate that SIRPalpha is a master regulator underlying tumor resistance to RT and provide proof-of-principle for SIRPalpha(-deficient) macrophage-based therapies to treat a broad spectrum of cancers, including those at advanced stages with low immunogenicity and metastases. |
