Abstract
Background?PD-1 ablation or PD-L1 specific monoclonal antibody against PD-1 can recruit the accumulation of functional T cells, leading to tumor rejection in the microenvironment and significantly improving the prognosis of various cancers. Despite these unprecedented clinical successes, intervention remission rates remain low after treatment, rarely exceeding 40%. The observation of PD-1/L1 blocking in patients is undoubtedly multifactorial, but the infiltrating degree of CD8+T cell may be an important factor for immunotherapeutic resistance. Methods:We proposed two computational algorithms to reveal the immune cell infiltration (ICI) landscape of 1646 lung adenocarcinoma patients. Three immune cell infiltration patterns were defined and the relative ICI scoring depended on principal-component analysis. Results:A high ICI score was associated with the increased tumor mutation burden and cell proliferation-related signaling pathways. Different cellular signaling pathways were observed in low ICI score subtypes, indicating active cell proliferation, and may be associated with poor prognosis. Conclusion:Our research identified that the ICI scores worked as an effective immunotherapy index, which may provide promising therapeutic strategies on immune therapeutics for lung adenocarcinoma.
Highlights
Lung cancer is a leading cause of death, resulting in the deaths of around 1.6 million people per year (Bray et al, 2018)
5-years overall survival rate of NSCLS is only about 27% and most non-small cell lung cancer (NSCLC) is diagnosed at the advanced stage, which contributes to the poor survival rate (Luo et al, 2019)
Based on the important role of TMB in clinical diagnosis, we aimed to study the correlation between TMB and immune cell infiltration (ICI) score to clarify the genetic imprinting of each ICI subgroup
Summary
Lung cancer is a leading cause of death, resulting in the deaths of around 1.6 million people per year (Bray et al, 2018). The over-activated inflammatory pathways play a crucial role in the tumorigenesis, which evolve into various cancer-related oncogenic pathways (Hanahan and Weinberg, 2011) These heterogeneities of cancers lead to the failure of therapy, and it is suggested that individual immunotherapy strategies may be helpful to improve the overall survival of cancer patients. PD-1 ablation or PD-L1 specific monoclonal antibody against PD-1 can recruit the accumulation of functional T cells, leading to tumor rejection in the microenvironment and significantly improving the prognosis of various cancers Despite these unprecedented clinical successes, intervention remission rates remain low after treatment, rarely exceeding 40%. The observation of PD-1/L1 blocking in patients is undoubtedly multifactorial, but the infiltrating degree of CD8+T cell may be an important factor for immunotherapeutic resistance
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