Comprehensive Analysis of the Tumor Microenvironment in Cutaneous Melanoma associated with Immune Infiltration

Accumulating evidence suggests that the malignant phenotypes of cancers are determined not only by the intrinsic properties of cancer cells but also by components in the tumor microenvironment (TME). In this study, we comprehensively characterized the TME of cutaneous melanoma (CM). As a result, tumor stage, tissue site, ulceration, thickness as well as patient age, sex were associated with immune infiltration. Patients of higher immune infiltration exhibited better survival outcomes, and antitumor effector cells, such as CD8 T cells and M1 macrophages, were found in significantly higher numbers in those tissues. Differential expression of mRNAs and long non-coding RNAs (lncRNAs) was analyzed and utilized to construct an immune-related competing endogenous RNA network, in which a lncRNA-associated subnetwork that could positively regulate the expression of IFN-gamma was highlighted. Functional analysis confirmed that this network was remarkably enriched in functional terms related to both immune response and tumor-intrinsic pathways. Finally, a total of 109 high-confidence prognostic genes were identified, and a gene module that contained several key immune checkpoint molecules or modulators (PD-1, PD-L1, PD-L2, and LCK) was screened, which confers survival benefit for CM patients as supported by both overall and relapse-free survival rates from different datasets.