| First Author | Huang C | Year | 2024 |
| Journal | Nat Cancer | Volume | 5 |
| Issue | 3 | Pages | 500-516 |
| PubMed ID | 38200243 | Mgi Jnum | J:346647 |
| Mgi Id | MGI:7618382 | Doi | 10.1038/s43018-023-00691-z |
| Citation | Huang C, et al. (2024) Sirpalpha on tumor-associated myeloid cells restrains antitumor immunity in colorectal cancer independent of its interaction with CD47. Nat Cancer 5(3):500-516 |
| abstractText | Immunosuppressive myeloid cells hinder immunotherapeutic efficacy in tumors, but the precise mechanisms remain undefined. Here, by performing single-cell RNA sequencing in colorectal cancer tissues, we found tumor-associated macrophages and granulocytic myeloid-derived suppressor cells increased most compared to their counterparts in normal tissue and displayed the highest immune-inhibitory signatures among all immunocytes. These cells exhibited significantly increased expression of immunoreceptor tyrosine-based inhibitory motif-bearing receptors, including SIRPA. Notably, Sirpa(-/-) mice were more resistant to tumor progression than wild-type mice. Moreover, Sirpalpha deficiency reprogramed the tumor microenvironment through expansion of TAM_Ccl8(hi) and gMDSC_H2-Q10(hi) subsets showing strong antitumor activity. Sirpa(-/-) macrophages presented strong phagocytosis and antigen presentation to enhance T cell activation and proliferation. Furthermore, Sirpa(-/-) macrophages facilitated T cell recruitment via Syk/Btk-dependent Ccl8 secretion. Therefore, Sirpalpha deficiency enhances innate and adaptive immune activation independent of expression of CD47 and Sirpalpha blockade could be a promising strategy to improve cancer immunotherapy efficacy. |
