論文 - 詳細
| RRC ID | 11812 |
|---|---|
| 著者 | Ding ZC, Blazar BR, Mellor AL, Munn DH, Zhou G. |
| タイトル | Chemotherapy rescues tumor-driven aberrant CD4+ T-cell differentiation and restores an activated polyfunctional helper phenotype. |
| ジャーナル | Blood |
| Abstract |
The functional development of tumor-specific CD4(+) T cells has a critical impact on the outcome of antitumor immune responses. Adoptive immunotherapy involving tumor-specific CD4(+) T cells has shown encouraging clinical benefits in some cancer patients. To mount an effective antitumor immunity, it is desirable to elicit activated type 1 T helper cells. Here, we report that type 1 T helper cell-like effector cells that arose in tumor-bearing hosts progressively expressed programmed death 1 during tumor growth. The programmed death 1(hi) effector cells displayed a dysfunctional phenotype, characterized by selective down-regulation of interleukin-7 receptor, heightened apoptosis, and poor antitumor efficacy. This tumor-driven aberrant T-cell response could be prevented by a single dose of the widely used chemotherapy agent cyclophosphamide. We show that chemotherapy conditioned the host environment, creating a transient window for optimal effector differentiation for adoptively transferred CD4(+) T cells. This robust effector differentiation, which was antigen-driven and mechanistically dependent on an intact host response to type I interferon, gave rise to activated polyfunctional T helper cells with high interleukin-7 receptor, rapid clonal expansion, and potent antitumor activity against established B-cell lymphomas. We hypothesize that prevention of tumor-induced effector cell dysfunction is a major mechanism contributing to the efficacy of combined chemoimmunotherapy. |
| 巻・号 | 115(12) |
| ページ | 2397-406 |
| 公開日 | 2010-3-25 |
| DOI | 10.1182/blood-2009-11-253336 |
| PII | S0006-4971(20)56590-7 |
| PMID | 20118405 |
| PMC | PMC2845898 |
| MeSH | Animals Antigens, Differentiation / metabolism Antineoplastic Agents, Alkylating / pharmacology* Apoptosis / drug effects Apoptosis / immunology Cell Differentiation / drug effects Cell Differentiation / immunology Combined Modality Therapy Cyclophosphamide / pharmacology* Female Forkhead Transcription Factors / metabolism Immunotherapy, Adoptive* Interferon Type I / metabolism Lymphoma, B-Cell / drug therapy Lymphoma, B-Cell / immunology Lymphoma, B-Cell / pathology Male Mice Mice, Inbred BALB C Mice, Transgenic Phenotype Programmed Cell Death 1 Receptor Receptors, Interleukin-7 / metabolism Recurrence Th1 Cells* / cytology Th1 Cells* / drug effects Th1 Cells* / transplantation Transplantation Conditioning / methods |
| IF | 17.794 |
| 引用数 | 48 |
| WOS 分野 | HEMATOLOGY |
| 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 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 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 | RBRC00904 |