Chun Jaemoo, Park Sang-Min, Lee Minsung, Ha In Jin, Jeong Mi-Kyung
KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea.
College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea.
Cancers (Basel). 2023 Jan 20;15(3):653. doi: 10.3390/cancers15030653.
Treatment strategies combining immune checkpoint inhibitors with sesquiterpene lactones have attracted much attention as a promising approach for cancer treatment. We systemically analyzed gene expression profiles of cells in response to two major sesquiterpene lactones, alantolactone and isoalantolactone, and determined whether the sesquiterpene lactone-rich fraction of L. (SFIH) enhances the antitumor effect of anti-PD-1 antibody in MC38 colorectal cancer-bearing mice. Gene expression and pathway analysis using RNA sequencing data were used to identify the SFIH-driven combined activity with anti-PD-1 antibody. The results showed that SFIH significantly enhanced the antitumor effect of anti-PD-1 antibody by reducing tumor growth and increasing the survival time of mice. Specifically, SFIH exhibited antitumor activity when combined with anti-PD-1 antibody, and the effects were further enhanced compared with monotherapy. An analysis of immune cells indicated that combination treatment with SFIH and anti-PD-1 antibody significantly increased the proportion of CD8 T cells. Moreover, combination treatment enhanced antitumor immunity by decreasing the population of myeloid-derived suppressor cells and increasing the number of M1-like macrophages. Pathway enrichment analysis revealed that combination therapy activated immune-related pathways to a greater extent than monotherapy. In conclusion, our integrative analysis demonstrates that SFIH enhances the response of murine tumors to anti-PD-1 antibody. These findings provide insight into developing integrative therapeutics and molecular data for the use of natural products as an adjunct treatment for colorectal cancer.
将免疫检查点抑制剂与倍半萜内酯相结合的治疗策略作为一种有前景的癌症治疗方法备受关注。我们系统分析了细胞对两种主要倍半萜内酯（土木香内酯和异土木香内酯）的基因表达谱，并确定了地锦草富含倍半萜内酯的组分（SFIH）是否能增强抗PD-1抗体对携带MC38结直肠癌小鼠的抗肿瘤作用。利用RNA测序数据进行基因表达和通路分析，以确定SFIH与抗PD-1抗体联合作用的活性。结果表明，SFIH通过抑制肿瘤生长和延长小鼠存活时间，显著增强了抗PD-1抗体的抗肿瘤作用。具体而言，SFIH与抗PD-1抗体联合使用时具有抗肿瘤活性，与单一疗法相比效果进一步增强。对免疫细胞的分析表明，SFIH与抗PD-1抗体联合治疗显著增加了CD8 T细胞的比例。此外，联合治疗通过减少髓源性抑制细胞的数量和增加M1样巨噬细胞的数量来增强抗肿瘤免疫力。通路富集分析显示，联合治疗比单一疗法更能激活免疫相关通路。总之，我们的综合分析表明，SFIH增强了小鼠肿瘤对抗PD-1抗体的反应。这些发现为开发综合疗法以及将天然产物用作结直肠癌辅助治疗的分子数据提供了见解。
