| 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
|
| リソース情報 |
| 実験動物マウス |
RBRC09485 |
