Research Paper Volume 14, Issue 11 pp 4786—4818

Figure 2. Immune landscape of LUAD and the TME characteristics. (A) Unsupervised clustering of LUAD patients from the TCGA cohort using ssGSEA scores from immune cell types. The “StromalScore” is the stromal signature that was designed to capture the presence of stroma in the tumor tissue. The “ImmuneScore” is the immune signature that aimed to represent the infiltration of immune cells in the tumor tissue. The “ESTIMATEScore” is the score combined by the stromal and immune scores. The “TumorPurity” is the tumor purity calculated by the nonlinear least squares method based on the ESTIMATEScore. The “Subtype” is the two clusters that were divided in the terms of the immune infiltration. The Immunity_H and Immunity_L subtypes showed the high and low immune infiltration, separately. (B) The ssGSEA scores in the differing TME immune phenotypes. The high immune infiltration group (Immunity_H) means the high StromalScore, ImmuneScore, ESTIMATEScore and low TumorPurity (all p<0.001). (C) Interaction of the TME immune cell types. The immune-related terms were clustered into 4 clusters according to the correlations among different immune-related terms. (D) The expressions of HLA genes in differing TME immune phenotypes. All HLA genes had significant differences in expression level between the high and low immune infiltration groups. (E) The expressions of CD274 gene in differing TME immune phenotypes. The expression of CD274 gene in the high immune infiltration group was significantly higher than that in the low immune infiltration group. (F) The fractions of the TME immune cells. The fractions of 8 immune cells had significant differences in two immune infiltration subgroups. (G) The associations of four immune cell types with overall survival. The high infiltration of aDCs, HLA, Mast_cells and T_cell_co.inhibition resulted in a higher OS of LUAD patients, respectively. (H) The relationships of immune infiltration status and survival status. The LUAD patients in the high immune infiltration group had a higher survival rate. (I) Responses of LUAD patients with differing TME immune phenotypes to immune therapy. The LUAD patients in the high immune infiltration group had significant response to anti-PD1-R. LUAD, lung adenocarcinoma; TME, tumor microenvironment; TCGA, the cancer genome atlas; ssGSEA, single-sample gene set enrichment analysis; OS, overall survival.