| 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
|
| リソース情報 |
| ヒト・動物細胞 |
NB9(RCB0477) |
