論文 - 詳細
| RRC ID | 86816 |
|---|---|
| 著者 | Zagorulya M, Yim L, Morgan DM, Edwards A, Torres-Mejia E, Momin N, McCreery CV, Zamora IL, Horton BL, Fox JG, Wittrup KD, Love JC, Spranger S. |
| タイトル | Tissue-specific abundance of interferon-gamma drives regulatory T cells to restrain DC1-mediated priming of cytotoxic T cells against lung cancer. |
| ジャーナル | Immunity |
| Abstract |
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-γ 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-γ 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. |
| 巻・号 | 56(2) |
| ページ | 386-405.e10 |
| 公開日 | 2023-2-14 |
| DOI | 10.1016/j.immuni.2023.01.010 |
| PII | S1074-7613(23)00020-1 |
| PMID | 36736322 |
| PMC | PMC10880816 |
| MeSH | CD8-Positive T-Lymphocytes Humans Interferon-gamma Lung Neoplasms* T-Lymphocytes, Cytotoxic T-Lymphocytes, Regulatory* |
| IF | 22.553 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 197 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| 実験動物マウス | RBRC09485 |