Takaku Shun, Shimizu Masumi, Morita Rimpei
Department of Microbiology and Immunology, Nippon Medical School, Tokyo 113-8602, Japan.
Center for Medical Education, Nippon Medical School, Tokyo 113-8602, Japan.
Evid Based Complement Alternat Med. 2023 Apr 28;2023:9630816. doi: 10.1155/2023/9630816. eCollection 2023.
Although Kampo-a traditional Japanese herbal medicine-contributes in the control of tumor growth in experimental animals, most of the antitumor effects are prophylactic and not therapeutic. In this study, we determined whether oral administration of an herbal mixture containing (WTMCGEP; , , , , , , and ), anecdotally used in Japan for the palliative care of patients with cancer, exhibits a therapeutic effect on tumor growth in a hypodermic murine CT26 colorectal tumor model. An tumor assay revealed that WTMCGEP extract has some direct influence over suppression of tumor growth. In wild-type BALB/c mice, WTMCGEP did not show any antitumor effect . However, in BALB-CD1d mice with partly mitigated immunosuppression by reason of them being devoid of both antitumoral type I and immunosuppressive type II natural killer T (NKT) cells, WTMCGEP therapeutically suppressed tumor growth. CD8 T cell depletion significantly accelerated tumor growth in WTMCGEP mice; therefore, its antitumor activity was primarily in a CD8 T cell-dependent manner. Regarding immunosuppressive cells in tumor-bearing CD1d mice, WTMCGEP did not influence the abundance of tumor-infiltrating CD4 and Forkhead box protein 3 regulatory T cells. However, it reduced both intratumoral and splenic Ly6G Ly6C polymorphonuclear myeloid-derived suppressor cells, which were most likely involved in tumor growth inhibition related to higher frequency of intratumoral CD107a CD8 T cells in these mice. Overall, these data illustrate that the deficiency of NKT cells urges WTMCGEP to exert a therapeutic antitumor effect mainly through CD8 T cells. Our efforts are the first to scientifically demonstrate the WTMCGEP's contribution to tumor immunity.
尽管日本传统草药汉方药在实验动物中有助于控制肿瘤生长，但大多数抗肿瘤作用是预防性的而非治疗性的。在本研究中，我们确定口服一种在日本用于癌症患者姑息治疗的草药混合物（WTMCGEP；含有 、 、 、 、 、 和 ）在皮下小鼠CT26结直肠癌肿瘤模型中是否对肿瘤生长具有治疗作用。一项肿瘤实验表明，WTMCGEP提取物对抑制肿瘤生长有一定的直接影响。在野生型BALB/c小鼠中，WTMCGEP未显示出任何抗肿瘤作用。然而，在因缺乏抗肿瘤I型和免疫抑制II型自然杀伤T（NKT）细胞而部分减轻免疫抑制的BALB-CD1d小鼠中，WTMCGEP在治疗上抑制了肿瘤生长。CD8 T细胞耗竭显著加速了WTMCGEP小鼠的肿瘤生长；因此，其抗肿瘤活性主要是以CD8 T细胞依赖的方式。关于荷瘤CD1d小鼠中的免疫抑制细胞，WTMCGEP不影响肿瘤浸润性CD4和叉头盒蛋白3调节性T细胞的丰度。然而，它减少了肿瘤内和脾脏中的Ly6G Ly6C多形核髓源性抑制细胞，这些细胞很可能与这些小鼠肿瘤内CD107a CD8 T细胞较高频率相关的肿瘤生长抑制有关。总体而言，这些数据表明NKT细胞的缺乏促使WTMCGEP主要通过CD8 T细胞发挥治疗性抗肿瘤作用。我们的研究首次科学地证明了WTMCGEP对肿瘤免疫的贡献。
