| First Author | Zagorulya M | Year | 2023 |
| Journal | Immunity | Volume | 56 |
| Issue | 2 | Pages | 386-405.e10 |
| PubMed ID | 36736322 | Mgi Jnum | J:339206 |
| Mgi Id | MGI:7437263 | Doi | 10.1016/j.immuni.2023.01.010 |
| Citation | Zagorulya M, et al. (2023) Tissue-specific abundance of interferon-gamma drives regulatory T cells to restrain DC1-mediated priming of cytotoxic T cells against lung cancer. Immunity 56(2):386-405.e10 |
| abstractText | Local environmental factors influence CD8(+) T cell priming in lymph nodes (LNs). Here, we sought to understand how factors unique to the tumor-draining mediastinal LN (mLN) impact CD8(+) T cell responses toward lung cancer. Type 1 conventional dendritic cells (DC1s) showed a mLN-specific failure to induce robust cytotoxic T cells responses. Using regulatory T (Treg) cell depletion strategies, we found that Treg cells suppressed DC1s in a spatially coordinated manner within tissue-specific microniches within the mLN. Treg cell suppression required MHC II-dependent contact between DC1s and Treg cells. Elevated levels of IFN-gamma drove differentiation Treg cells into Th1-like effector Treg cells in the mLN. In patients with cancer, Treg cell Th1 polarization, but not CD8(+)/Treg cell ratios, correlated with poor responses to checkpoint blockade immunotherapy. Thus, IFN-gamma in the mLN skews Treg cells to be Th1-like effector Treg cells, driving their close interaction with DC1s and subsequent suppression of cytotoxic T cell responses. |
