Theranostics 2021; 11(15):7175-7187. doi:10.7150/thno.59056 This issue Cite

Research Paper

CXCL10 potentiates immune checkpoint blockade therapy in homologous recombination-deficient tumors

Zhiwen Shi1,2, Jianfeng Shen3,4, Junjun Qiu1,2, Qingguo Zhao1, Keqin Hua1,2✉, Hongyan Wang1,2,5✉

1. Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regualtion, Shanghai Institute of Planned Parenthood Research, State Key Laboratory of Genetic Engineering at School of Life Sciences, Institute of Reproduction and Development, Fudan University, Shanghai 200032, China.
2. Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Institute of Metabolism and Integrative Biology, Institutes of Biomedical Sciences, Fudan University, Shanghai 200433, China.
3. Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200025, China.
4. Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, 200025, China.
5. Children's Hospital of Fudan University, Shanghai 201100, China.

Citation:
Shi Z, Shen J, Qiu J, Zhao Q, Hua K, Wang H. CXCL10 potentiates immune checkpoint blockade therapy in homologous recombination-deficient tumors. Theranostics 2021; 11(15):7175-7187. doi:10.7150/thno.59056. https://www.thno.org/v11p7175.htm
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Abstract

Graphic abstract

Background: Homologous recombination deficiency (HRD) is a common molecular characteristic of genomic instability, and has been proven to be a biomarker for target therapy. However, until now, no research has explored the changes in the transcriptomics landscape of HRD tumors.

Methods: The HRD score was established from SNP array data of breast cancer patients from the cancer genome atlas (TCGA) database. The transcriptome data of patients with different HRD scores were analyzed to identify biomarkers associated with HRD. The candidate biomarkers were validated in the gene expression omnibus (GEO) database and immunotherapy cohorts.

Results: Based on data from the gene expression profile and clinical characteristics from 1310 breast cancer patients, including TCGA database and GEO database, we found that downstream targets of the cGAS-STING pathway, such as CXCL10, were upregulated in HRD tumors and could be used as a predictor of survival outcome in triple-negative breast cancer (TNBC) patients. Further comprehensive analysis of the tumor immune microenvironment (TIME) revealed that the expression of CXCL10 was positively correlated with neoantigen load and infiltrating immune cells. Finally, in vivo experimental data and clinical trial data confirmed that the expression of CXCL10 could be used as a biomarker for anti-PD-1/PD-L1 therapy.

Conclusions: Together, our study not only revealed that CXCL10 is associated with HRD but also introduced a potential new perspective for identifying prognostic biomarkers of immunotherapy.

Keywords: HRD, cGAS-STING, TIME, CXCL10, immunotherapy


Citation styles

APA
Shi, Z., Shen, J., Qiu, J., Zhao, Q., Hua, K., Wang, H. (2021). CXCL10 potentiates immune checkpoint blockade therapy in homologous recombination-deficient tumors. Theranostics, 11(15), 7175-7187. https://doi.org/10.7150/thno.59056.

ACS
Shi, Z.; Shen, J.; Qiu, J.; Zhao, Q.; Hua, K.; Wang, H. CXCL10 potentiates immune checkpoint blockade therapy in homologous recombination-deficient tumors. Theranostics 2021, 11 (15), 7175-7187. DOI: 10.7150/thno.59056.

NLM
Shi Z, Shen J, Qiu J, Zhao Q, Hua K, Wang H. CXCL10 potentiates immune checkpoint blockade therapy in homologous recombination-deficient tumors. Theranostics 2021; 11(15):7175-7187. doi:10.7150/thno.59056. https://www.thno.org/v11p7175.htm

CSE
Shi Z, Shen J, Qiu J, Zhao Q, Hua K, Wang H. 2021. CXCL10 potentiates immune checkpoint blockade therapy in homologous recombination-deficient tumors. Theranostics. 11(15):7175-7187.

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