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

  • Heliyon. 2023 Sep 14;9(9):e19760. doi: 10.1016/j.heliyon.2023.e19760.
Wangyou Feng  1 ,  Dongbo Jiang  2 ,  Ying Xu  1 ,  Yuanfeng Li  1 ,  Lin Chen  1 ,  Minye Zhao  1 ,  Yujie Shen  1 ,  Wenjing Liao  1 ,  Hong Yang  1 ,  Jia Li  1
Affiliations
  • 1. Department of Gynaecology and Obstetrics, Xijing Hospital, Air Force Medical University (the Fourth Military Medical University), 15 Changle Western Road, Xi'an, 710032, Shaanxi, China.
  • 2. Department of Immunology, School of Basic Medicine, Air Force Medical University (the Fourth Military Medical University), 169 Changle Western Road, Xi'an, 710032, Shaanxi, China.
PMID: 37809574 DOI: 10.1016/j.heliyon.2023.e19760
Abstract

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.

Keywords
And prognosis; CDK4/6i; Immunotherapy; PD1 antibody; TLS.
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