論文 - 詳細
| RRC ID | 86981 |
|---|---|
| 著者 | Steele MM, Jaiswal A, Delclaux I, Dryg ID, Murugan D, Femel J, Son S, du Bois H, Hill C, Leachman SA, Chang YH, Coussens LM, Anandasabapathy N, Lund AW. |
| タイトル | T cell egress via lymphatic vessels is tuned by antigen encounter and limits tumor control. |
| ジャーナル | Nat Immunol |
| Abstract |
Antigen-specific CD8+ T cell accumulation in tumors is a prerequisite for effective immunotherapy, and yet the mechanisms of lymphocyte transit are not well defined. Here we show that tumor-associated lymphatic vessels control T cell exit from tumors via the chemokine CXCL12, and intratumoral antigen encounter tunes CXCR4 expression by effector CD8+ T cells. Only high-affinity antigen downregulates CXCR4 and upregulates the CXCL12 decoy receptor, ACKR3, thereby reducing CXCL12 sensitivity and promoting T cell retention. A diverse repertoire of functional tumor-specific CD8+ T cells, therefore, exit the tumor, which limits the pool of CD8+ T cells available to exert tumor control. CXCR4 inhibition or loss of lymphatic-specific CXCL12 boosts T cell retention and enhances tumor control. These data indicate that strategies to limit T cell egress might be an approach to boost the quantity and quality of intratumoral T cells and thereby response to immunotherapy. |
| 巻・号 | 24(4) |
| ページ | 664-675 |
| 公開日 | 2023-4-1 |
| DOI | 10.1038/s41590-023-01443-y |
| PII | 10.1038/s41590-023-01443-y |
| PMID | 36849745 |
| PMC | PMC10998279 |
| MeSH | CD8-Positive T-Lymphocytes Humans Immunotherapy Lymphatic Vessels* / metabolism Neoplasms* / pathology Neoplasms* / therapy Receptors, CXCR4 / metabolism |
| IF | 20.479 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 195 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC05737 |