Tumor Immunogenicity Score Impacts Immunotherapy Response

ON2019-11-28TAG: ShanghaiTech UniversityCATEGORY: School of Life Science and Technology

A tumor immunogenicity score (TIGS), a novel cancer immunotherapy biomarker, was proposed by a research team from the School of Life Science and Technology (SLST) led by Assistant Professor Liu Xuesong. The study describing TIGS was published online in the journal eLife on November 26th. 

This tumor immunogenicity-based biomarker could guide the treatment to transform some immunotherapy non-responsive tumors to immunotherapy responsive tumors. Stimulating antigen processing and presentation pathway could enhance tumor immunogenicity, and possibly cancer immunotherapy responsiveness.

Cancer Immunotherapy, represented by immune checkpoint inhibitors, is transforming cancer treatment. Immune checkpoint inhibitors, such as anti-PD1 antibody, anti-PD-L1 antibody and anti-CTLA-4 antibody, have successfully cured some late stage and originally thought to be incurable cancers, such as melanoma and lung cancer. However, less than 20% of patients show response to immune checkpoint inhibitors, and there is an unmet need for biomarkers that will identify patients more likely to respond to immunotherapy. 

In order to explore the fundamental factors determining the clinical response to tumor immunotherapy, Dr. Liu Xuesong and colleagues put forward a hypothesis: the immunogenicity of tumor cells is the key factor determining whether tumors respond to immunotherapy, and the immunogenicity of tumors can be decomposed into two independent factors: “tumor antigenicity” and “antigen presentation ability.” 

Evidence has been provided to show that TIGS is a robust pan-cancer applicable immunotherapy response prediction biomarker. TIGS show improved performance compared with currently known cancer immunotherapy response prediction biomarkers TMB, IFG, PD-L1, etc. (Figure 1). TIGS can also predict cancer immunotherapy objective response rate in various cancer types (Figure 2). 

Wang Shixiang, a 4th-year SLST graduate student, is the first author and Professor Liu Xuesong is the corresponding author. Graduate students He Zaoke, Wang Xuan and Li Huimin from the Liu group participated in the study. This work was supported by the National Natural Science Foundation of China and ShanghaiTech University.

Read more at: https://elifesciences.org/articles/49020

Figure 1. TIGS predicts ICI immunotherapy clinical response

Figure 2. TIGS and predicted pan-cancer response rates to PD-1 inhibition