P1.04-21 Cellular Landscape of Normal Adjacent to Tumor Microenvironment in Non-Small Cell Lung Cancer

Abstract

Cellular heterogeneity is the dominant ingredient in tumor microenvironment, which plays essential roles in cancer malignancy. Growing evidence have shed light on the important role of tumor-infiltrating immune and stromal cells in cancer progression. Here, we portrayed the cellular landscape of a total of 64 cell types in 313 normal lung tissues, 110 adjacent normal tissues and 992 non-small cell lung cancer (NSCLC) tissues using transcriptomic data by integrated bioinformatics analysis. In general, adjacent normal tissues presented an intermediate state between normal and tumor tissues, which was that the fraction of immune cells decreased while fraction of stromal cells increased from normal, adjacent to tumor tissues. Moreover, huge difference of tumor-infiltrating cells were detected between lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Interestingly, in LUAD, rather than in LUSC, subtypes of CD4+ and CD8+ T cells were significant higher in tumor tissues compared with adjacent and normal tissues. Stromal cells, such as fibroblast and endothelial cells, also showed great diversity among the normal, adjacent and tumor tissues. Moreover, immune inhibitory receptors (PD1, CTLA4, LAG3 and TIM3) were more commonly co-expressed on certain subtypes of T cells in both LUAD and LUSC compared with adjacent normal tissues. Besides, significant clinical relevance between tumor-infiltrating cells and tumor stages were more prevalence in LUAD, compared with LUSC. Lastly, there were 45 cell types and 27 cell types were significantly correlated with patients overall survival in LUAD and LUSC, respectively. Surprisingly, certain subtypes of T cells were adverse prognosis factors for NSCLC. Taken together, we built powerful prognosis predictors for LUAD and LUSC patient using tumor-infiltrating cells. In summary, our analysis provided extensive details of cellular landscape in normal adjacent to tumor tissues in NSCLC and how they were involved in tumor progression. Better understanding of the complex crosstalk between tumor cells and infiltrating cells might provide novel therapeutic targets and biomarker for NSCLC, especially in the immune therapies.