| First Author | Shi H | Year | 2024 |
| Journal | J Exp Med | Volume | 221 |
| Issue | 12 | PubMed ID | 39470607 |
| Mgi Jnum | J:359872 | Mgi Id | MGI:7766081 |
| Doi | 10.1084/jem.20240797 | Citation | Shi H, et al. (2024) Suppression of melanoma by mice lacking MHC-II: Mechanisms and implications for cancer immunotherapy. J Exp Med 221(12) |
| abstractText | Immune checkpoint inhibitors interfere with T cell exhaustion but often fail to cure or control cancer long-term in patients. Using a genetic screen in C57BL/6J mice, we discovered a mutation in host H2-Aa that caused strong immune-mediated resistance to mouse melanomas. H2-Aa encodes an MHC class II alpha chain, and its absence in C57BL/6J mice eliminates all MHC-II expression. H2-Aa deficiency, specifically in dendritic cells (DC), led to a quantitative increase in type 2 conventional DC (cDC2) and a decrease in cDC1. H2-Aa-deficient cDC2, but not cDC1, were essential for melanoma suppression and effectively cross-primed and recruited CD8 T cells into tumors. Lack of T regulatory cells, also observed in H2-Aa deficiency, contributed to melanoma suppression. Acute disruption of H2-Aa was therapeutic in melanoma-bearing mice, particularly when combined with checkpoint inhibition, which had no therapeutic effect by itself. Our findings suggest that inhibiting MHC-II may be an effective immunotherapeutic approach to enhance immune responses to cancer. |
