Antigen presentation and tumor immunogenicity in cancer immunotherapy response prediction

Author:

Wang Shixiang123ORCID,He Zaoke123,Wang Xuan123,Li Huimin123,Liu Xue-Song1ORCID

Affiliation:

1. School of Life Science and Technology, ShanghaiTech University, Shanghai, China

2. Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China

3. University of Chinese Academy of Sciences, Beijing, China

Abstract

Immunotherapy, represented by immune checkpoint inhibitors (ICI), is transforming the treatment of cancer. However, only a small percentage of patients show response to ICI, and there is an unmet need for biomarkers that will identify patients who are more likely to respond to immunotherapy. The fundamental basis for ICI response is the immunogenicity of a tumor, which is primarily determined by tumor antigenicity and antigen presentation efficiency. Here, we propose a method to measure tumor immunogenicity score (TIGS), which combines tumor mutational burden (TMB) and an expression signature of the antigen processing and presenting machinery (APM). In both correlation with pan-cancer ICI objective response rates (ORR) and ICI clinical response prediction for individual patients, TIGS consistently showed improved performance compared to TMB and other known prediction biomarkers for ICI response. This study suggests that TIGS is an effective tumor-inherent biomarker for ICI-response prediction.

Funder

National Natural Science Foundation of China

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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