Checkpoint blockade drugs have recently achieved remarkable success in treating late stage melanoma, non-small cell lung carcinomas and renal cell carcinomas. This breakthrough stimulated more than two hundred clinical trials involving anti-CTLA4 or anti-PD-1/PD-L1 drugs over 20 human cancers worldwide in the past few years. Although many patients have shown promising results in Phase I/II trials, a substantial fraction failed to respond. Efforts have been made to elucidate the functions of selected immune cells and provide prognostic predictors. However, the clinical impact of other immune cells in many cancers remains poorly understood. We integrated high-throughput molecular profiles combined with clinical data to systematically model six immune components in the tumor microenvironment in over 10,000 samples across 23 cancer types. We showed that lymphocyte infiltration generally associates with better outcome, while tumor associated myelocytes are negative prognostic predictors. We identified diverse associations between tumor-infiltrating immune cells and patient clinical features, including patient survival, disease recurrence, clinical stage, age, gender and viral infection status. We found immune cell infiltration to be correlated with somatic mutation load and microsatellite instability (MSI) status, suggesting the mechanism of immunosurveillance. We observed correlation between cancer/testis antigen MAGEA3 expression with CD8 T-cell infiltration in melanoma but not in non-small cell lung carcinomas (NSCLC), and implicated CTAGE1 and CALR3 as alternative candidates for cancer vaccines in NSCLC. Furthermore, we found PD-1 and CTLA4 expression to be associated with CD8 T-cell level in most cancers with exceptions in glioblastoma and ovarian cancer, suggesting cancer-specific usage of checkpoint blockade drugs. Our study indicates that systematic analysis of tumor immunity has the potential to inform effective cancer vaccines and checkpoint blockade therapies.
Citation Format: Bo Li, Jun Liu, X. Shirley Liu. Comprehensive analyses of tumor immunity with implications to cancer immunotherapies. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B162.
- ©2016 American Association for Cancer Research.