PD-1 monoclonal antibodies enhance the cryoablation-induced antitumor immune response: a breast cancer murine model research

Abstract

Background

It has been demonstrated that cryoablation (Cryo) causes specific T-cell immune responses in the body; however, it is not sufficient to prevent tumor recurrence and metastasis. In this report, we evaluated changes in the tumor immune microenvironment (TIME) in distant tumor tissues after Cryo and investigated the immunosuppressive mechanisms that limit the efficacy of Cryo.

Methods

Bilateral mammary tumor models were established in mice, and we first observed the dynamic changes in immune cells and cytokines at different time points after Cryo. Then, we confirmed that the upregulation of PD-1 and PD-L1 signaling in the contralateral tumor tissue was closely related to the immunosuppressive state in the TIME at the later stage after Cryo. Finally, we also evaluated the synergistic antitumor effects of Cryo combined with PD-1 monoclonal antibody (mAb) in the treatment of breast cancer (BC) mouse.

Results

We found that Cryo can stimulate the body’s immune response, but it also induces immunosuppression. The elevated PD-1/PD-L1 expression in distant tumor tissues at the later stage after Cryo was closely related to the immunosuppressive state in the TIME but also created the conditions for Cryo combined with PD-1 mAb for BC mouse treatment. Cryo + PD-1 mAb could improve the immunosuppressive state of tumors and enhance the Cryo-induced immune response, thus exerting a synergistic antitumor effect.

Conclusions

The PD-1/PD-L1 axis plays an important role in suppressing Cryo-induced antitumor immune responses. This study provides a theoretical basis for Cryo combined with PD-1 mAb therapy in clinical BC patients.

Keywords:

• PD-1 monoclonal antibodies
• cryoablation
• breast cancer
• immune response
• immunosuppression

Ethical approval

The study was approved by the ethics committee of The Affiliated Suzhou Hospital of Nanjing Medical University.

Author contributions

Substantial contributions to conception and design: Z.-P.Y., X.-W.S., Y.-P.H., J.G. and Y.J.; acquisition of data: Z.-P.Y., X.-W.S., Y.-P.H.; analysis and interpretation of data: Z.-P.Y., Y.-P.H., J.G. and Y.J.; drafting and revision of the article: Z.-P.Y. and Y.J. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Research data can be obtained from the corresponding authors upon reasonable request.

Additional information

Funding

This study was funded by the Suzhou Medical and health application technology innovation project (grant numbers SKJYD2021086), Suzhou Basic Research Application (grant numbers SYSD2020080), Maternal and child health scientific research project of Jiangsu Province (grant numbers FYX202019).