Abstract
Even with the great advances in immunotherapy in recent years, the response rate to immune checkpoint inhibitor therapy for non-small cell lung cancer is only about 20%. We aimed to identify new features that would better predict which patients can benefit from an immune checkpoint blocker. This study is based on the publicly available gene expression data from The Cancer Genome Atlas lung cancer samples and the newly released mutation annotation data. We performed a comprehensive analysis by correlating patient cytolytic activity index, mutational signatures, and other immune characteristics in four stratified patient groups. The results cytolytic activity index are highly correlated with immune infiltration scores, T cell infiltration scores and TCR clonality scores in lung cancer. In addition, we observed that the mutational event signatures might play a more important role in predicting immunotherapy response in squamous cell carcinoma and two subgroups of adenocarcinomas. Our analysis illustrates the utility of integrating both tumor immune and genomic landscape for a better understanding of immune response in lung cancer.
Highlights
Non-small cell lung cancer (NSCLC) accounts for more than 85% of incidences of lung cancers
Through correlating all the derived immune, genomic and clinical metrics, we address several questions: how cytolytic activity in lung cancer correlate with mutation load; do the patient stratification analyses based on cytolytic activity and tumor mutational signatures reflect different mechanisms of
Based on the initial analysis provided at COSMIC, there are seven major mutational signatures presented in Lung Adenocarcinoma (LUAD) samples and five major signatures in Lung Squamous Cell Carcinoma (LUSC), which are possibly associated with smoking, age, APOBEC, etc
Summary
Non-small cell lung cancer (NSCLC) accounts for more than 85% of incidences of lung cancers. Even with the great advances in immunotherapy in recent years, the response rate to immune checkpoint inhibitor therapy for NSCLC, such as anti-PD1/PDL1 therapy, is only about 20%. A key concept in cancer immunotherapy is that cancer malignant cells, which would normally be recognized by T cells, can develop mechanisms to evade the human immune system by disrupting checkpoint molecules. The goal of effective immunotherapy is to restore the ability of the immune system to detect and attack cancer cells. A better understanding of how tumor cells and immune cells interact and contribute to the tumor microenvironment is crucial in improving the efficacy of immunotherapy and in developing alternative treatments. Tumor cells express antigens that can be recognized by immune cells such as T cells and B cells. Cancer researchers are interested in whether there is sufficient amount of infiltrating lymphocytes in tumor tissues, their cell type distribution, and what proportion of these
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