Optimal timing and sequence of combining stereotactic radiosurgery with immune checkpoint inhibitors in treating brain metastases: clinical evidence and mechanistic basis

Wentao Tian; Xianjing Chu; Guilong Tanzhu; Rongrong Zhou

doi:10.1186/s12967-023-04089-4

Optimal timing and sequence of combining stereotactic radiosurgery with immune checkpoint inhibitors in treating brain metastases: clinical evidence and mechanistic basis

J Transl Med. 2023 Apr 5;21(1):244. doi: 10.1186/s12967-023-04089-4.

Authors

Wentao Tian^#¹, Xianjing Chu^#¹, Guilong Tanzhu¹, Rongrong Zhou^{2

3

4}

Affiliations

¹ Department of Oncology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, 410008, China.
² Department of Oncology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, Changsha, 410008, China. zhourr@csu.edu.cn.
³ Xiangya Lung Cancer Center, Xiangya Hospital, Central South University, Changsha, 410008, China. zhourr@csu.edu.cn.
⁴ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China. zhourr@csu.edu.cn.

^# Contributed equally.

Abstract

Recent evidence has shown that immune checkpoint inhibitors (ICIs) are efficacious for treating brain metastases of various primary tumors. However, the immunosuppressive tumor microenvironment and the blood-brain barrier (BBB) or blood-tumor barrier (BTB) essentially restrict the efficacy of ICIs. Stereotactic radiosurgery (SRS) can be a powerful ally to ICIs due to its trait of disrupting the BBB/BTB and increasing the immunogenicity of brain metastases. The combination of SRS + ICI has shown synergy in brain metastases in several retrospective studies. Nevertheless, the optimal schedule for the combination of SRS and ICI in brain metastases is yet to be determined. In this review, we summarized the current clinical and preclinical evidence on the timing and sequence of SRS + ICI to provide insight into the current state of knowledge about this important area in patient care.

Keywords: Brain metastases; Cancer combination therapy; Immune checkpoint inhibitors; Stereotactic radiosurgery.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Brain Neoplasms* / pathology
Humans
Immune Checkpoint Inhibitors
Immunosuppressive Agents
Radiosurgery*
Retrospective Studies
Tumor Microenvironment

Substances

Immune Checkpoint Inhibitors
Immunosuppressive Agents