論文 - 詳細
| RRC ID | 86506 |
|---|---|
| 著者 | Yokomura M, Nagano S, Kawamoto H, Hirohashi Y, Torigoe T, Asakage T, Katayama R. |
| タイトル | Afatinib exerts an inhibitory effect on T cell-mediated cytotoxicity. |
| ジャーナル | Cancer Immunol Immunother |
| Abstract |
Adoptive T cell therapy has shown significant efficacy in cancer treatment, especially in hematologic malignancies, and is increasingly being explored for solid cancers. Combining T cell therapy with conventional treatments holds promise for enhancing therapeutic effects. In this study, we conducted an in vitro inhibitor screening to evaluate the effects of various inhibitors on T cell-mediated cytotoxic activity against cancer cells. Among the candidates, we identified afatinib as an immunosuppressive agent that attenuates T cell cytotoxic activity by reducing interferon-γ (IFN-γ) secretion and suppressing T cell activation. Notably, this IFN-γ reduction was independent of T cell proliferation. RNA-seq analysis revealed that afatinib downregulated the T cell receptor (TCR) pathway signature. RT-qPCR demonstrated a dose-dependent suppression of IFNG mRNA expression in afatinib-treated T cells. Furthermore, afatinib impaired tumor rejection in an immunological memory mouse model that had been previously cured by anti-PD-L1 therapy, suggesting that afatinib may inhibit the function of effector memory T cells. Collectively, our findings highlight afatinib's potential to impair T cell effector functions, indicating that strategic consideration is essential when combining epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), including afatinib, with adoptive T cell therapies. |
| 巻・号 | 75(1) |
| ページ | 33 |
| 公開日 | 2026-1-3 |
| DOI | 10.1007/s00262-025-04279-7 |
| PII | 10.1007/s00262-025-04279-7 |
| PMID | 41484217 |
| PMC | PMC12764737 |
| MeSH | Afatinib* / pharmacology Animals Cell Line, Tumor Cytotoxicity, Immunologic* / drug effects Humans Immunotherapy, Adoptive* / methods Interferon-gamma / metabolism Lymphocyte Activation / drug effects Mice Receptors, Antigen, T-Cell T-Lymphocytes* / drug effects T-Lymphocytes* / immunology T-Lymphocytes, Cytotoxic* / drug effects T-Lymphocytes, Cytotoxic* / immunology |
| IF | 5.442 |
| 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 | Bluesky |
| 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 | |
| ヒト・動物細胞 | NB9(RCB0477) |