CDK4/6i enhances the antitumor effect of PD1 antibody by promoting TLS formation in ovarian cancer

• Published in: Heliyon 2023-09, Vol.9 (9), p.e19760-e19760, Article e19760
• Main Authors: Feng, Wangyou, Jiang, Dongbo, Xu, Ying, Li, Yuanfeng, Chen, Lin, Zhao, Minye, Shen, Yujie, Liao, Wenjing, Yang, Hong, Li, Jia
• Format: Article
• Language: English
• Subjects: And prognosis; CDK4/6i; Immunotherapy; PD1 antibody; TLS
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2023.e19760

Ovarian cancer is insensitive to immunotherapy and has a high mortality rate. CDK4/6 inhibitors (CDK4/6i) regulate the tumor microenvironment and play an antitumor role. Our previous research demonstrated that lymphocyte aggregation (tertiary lymphoid structures, TLSs) was observed after CDK4/6i treatment. This may explain the synergistic action of CDK4/6i with the anti-PD1 antibody. However, the key mechanism by which CDK4/6i promotes TLS formation has not been elucidated. We examine the link between TLS and prognosis. Animal models and high-throughput sequencing were used to explore the potential mechanism by which CDK4/6i promotes TLS formation. Our results showed the presence of TLSs was associated with a favorable prognosis for ovarian cancer. CDK4/6i promoted TLS formation and enhanced the immunotherapeutic effect of the anti-PD1 antibody. The potential mechanism of CDK4/6i affecting the formation of TLS may be through modulating SCD1 and its regulatory molecules ATF3 and CCL4. Our findings provide a theoretical basis for the application of CDK4/6i in ovarian cancer. •High TLS formation is associated with a better prognosis in ovarian cancer patients.•CDK4/6i promoted TLS formation by downregulating SCD1 expression and enhanced the immunotherapeutic effect of the anti-PD1 antibody.