Chun Jaemoo, Park Sang-Min, Yi Jin-Mu, Ha In Jin, Kang Han Na, Jeong Mi-Kyung
KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon, South Korea.
KM Data Division, Korea Institute of Oriental Medicine, Daejeon, South Korea.
Front Pharmacol. 2022 Jul 6;13:901563. doi: 10.3389/fphar.2022.901563. eCollection 2022.
Immune checkpoint blockage targeting PD-L1 has led to breakthroughs in cancer treatment. Although anti-PD-L1-based immunotherapy has been approved as standard therapy in various cancer types, its therapeutic efficacy in most colorectal cancers (CRC) is still limited due to the low response to immunotherapy. Therefore, combining treatment with herbal medicines could be an alternative approach for treating CRC to overcome this limitation. Bojungikki-Tang (BJIKT), a herbal formula used in traditional Chinese medicine, clinically improves the quality of life for cancer patients and has been associated with antitumor and immune-modulating activities. However, the regulatory effect of BJIKT on the immune response in the tumor microenvironment remains largely uninvestigated. In this study, we verified the inhibitory effect of BJIKT on tumor growth and investigated the regulatory effect of combination therapy with BJIKT and anti-PD-L1 on antitumor immune responses in an MC38 CRC-bearing C57BL/6 mouse model. Immune profiling analysis by flow cytometry was used to characterize the exact cell types contributing to anticancer activities. Combination treatment with BJIKT and anti-PD-L1 therapy significantly suppressed tumor growth in MC38-bearing mice and increased the proportion of cytotoxic T lymphocytes and natural killer cells in tumor tissues. Furthermore, BJIKT suppressed the population of myeloid-derived suppressor cells, suggesting that this combination treatment effectively regulates the immunological function of T-cells by improving the tumor microenvironment. The herbal formula BJIKT can be a novel therapeutic option for improving anti-PD-L1-based immunotherapy in patients with CRC.
靶向程序性死亡配体1（PD-L1）的免疫检查点阻断已在癌症治疗领域取得突破。尽管基于抗PD-L1的免疫疗法已被批准作为多种癌症类型的标准疗法，但由于对免疫疗法的低反应性，其在大多数结直肠癌（CRC）中的治疗效果仍然有限。因此，联合使用草药治疗可能是克服这一局限性、治疗CRC的一种替代方法。补中益气汤（BJIKT）是一种传统中药方剂，临床上可改善癌症患者的生活质量，并与抗肿瘤和免疫调节活性相关。然而，BJIKT对肿瘤微环境中免疫反应的调节作用在很大程度上仍未得到研究。在本研究中，我们验证了BJIKT对肿瘤生长的抑制作用，并研究了BJIKT与抗PD-L1联合治疗对MC38荷瘤C57BL/6小鼠模型抗肿瘤免疫反应的调节作用。通过流式细胞术进行免疫谱分析，以确定对抗癌活性有贡献的确切细胞类型。BJIKT与抗PD-L1联合治疗显著抑制了荷MC38小鼠的肿瘤生长，并增加了肿瘤组织中细胞毒性T淋巴细胞和自然杀伤细胞的比例。此外，BJIKT抑制了髓源性抑制细胞的数量，表明这种联合治疗通过改善肿瘤微环境有效地调节了T细胞的免疫功能。中药方剂BJIKT可能是改善CRC患者基于抗PD-L1免疫疗法的一种新的治疗选择。
