| First Author | Moreno Ayala MA | Year | 2023 |
| Journal | Immunity | Volume | 56 |
| Issue | 7 | Pages | 1613-1630.e5 |
| PubMed ID | 37392735 | Mgi Jnum | J:338374 |
| Mgi Id | MGI:7511349 | Doi | 10.1016/j.immuni.2023.06.003 |
| Citation | Moreno Ayala MA, et al. (2023) CXCR3 expression in regulatory T cells drives interactions with type I dendritic cells in tumors to restrict CD8(+) T cell antitumor immunity. Immunity 56(7):1613-1630.e5 |
| abstractText | Infiltration of regulatory T (Treg) cells, an immunosuppressive population of CD4(+) T cells, into solid cancers represents a barrier to cancer immunotherapy. Chemokine receptors are critical for Treg cell recruitment and cell-cell interactions in inflamed tissues, including cancer, and thus are an ideal therapeutic target. Here, we show in multiple cancer models that CXCR3(+) Treg cells were increased in tumors compared with lymphoid tissues, exhibited an activated phenotype, and interacted preferentially with CXCL9-producing BATF3(+) dendritic cells (DCs). Genetic ablation of CXCR3 in Treg cells disrupted DC1-Treg cell interactions and concomitantly increased DC-CD8(+) T cell interactions. Mechanistically, CXCR3 ablation in Treg cells increased tumor antigen-specific cross-presentation by DC1s, increasing CD8(+) T cell priming and reactivation in tumors. This ultimately impaired tumor progression, especially in combination with anti-PD-1 checkpoint blockade immunotherapy. Overall, CXCR3 is shown to be a critical chemokine receptor for Treg cell accumulation and immune suppression in tumors. |
