The tumor immune microenvironmental analysis of 2,033 transcriptomes across 7 cancer types

Abstract

Understanding the tumor microenvironment is important to efficiently identify appropriate patients for immunotherapies in a variety of cancers. Here, we presented the tumor microenvironmental analysis of 2,033 cancer samples across 7 cancer types: colon adenocarcinoma, skin cutaneous melanoma, kidney renal papillary cell carcinoma, sarcoma, pancreatic adenocarcinoma, glioblastoma multiforme, and pheochromocytoma / paraganglioma from The Cancer Genome Atlas cohort. Unsupervised hierarchical clustering based on the gene expression profiles separated the cancer samples into two distinct clusters, and characterized those into immune-competent and immune-deficient subtypes using the estimated abundances of infiltrated immune and stromal cells. We demonstrated differential tumor microenvironmental characteristics of immune-competent subtypes across 7 cancer types, particularly immunosuppressive tumor microenvironment features in kidney renal papillary cell carcinoma with significant poorer survival rates and immune-supportive features in sarcoma and skin cutaneous melanoma. Additionally, differential genomic instability patterns between the subtypes were found across the cancer types, and discovered that immune-competent subtypes in most of cancer types had significantly higher immune checkpoint gene expressions. Overall, this study suggests that our subtyping approach based on transcriptomic data could contribute to precise prediction of immune checkpoint inhibitor responses in a wide range of cancer types.

Integrative Genomic and Transcriptomic Analyses of Tumor Suppressor Genes and Their Role on Tumor Microenvironment and Immunity in Lung Squamous Cell Carcinoma

“…The correlation between immune and stromal scores along with the TMB values among four TSG subgroups indicated that the stromal and immune cells were strongly correlated with the mutational burden regardless of subtype, which was consistent with previous results that the tumor cells with high TMB and the formation of neoantigens had a decisive effect on the defective immune system and TME including tumor immunogenicity ( 22 , 34 ).…”

“…The data preprocessing was performed by the previously reported pipeline ( 20 – 22 ). The number of raw reads (HTSeq count for Ensembl annotated gene) was transformed to variance transformed data (R package ‘DESeq2’) for transcriptomic sequencing analysis.…”

Identification of a Tumor Microenvironment‐Related Gene Signature Indicative of Disease Prognosis and Treatment Response in Colon Cancer

“…The tumor microenvironment (TME), defined as the tissue environment surrounding a tumor, plays an important role in the tumorigenesis and prognosis of colon cancer. The TME contains not only cancer cells but also noncancer cells, including components of the extracellular matrix, blood vessels, immune cells, neurons, and cells that perform other tissue functions; these cell types all contribute to the malignant phenotypes of cancer, including uncontrolled proliferation, resistance to apoptosis, and evasion of immune surveillance [ 5 , 6 ]. Thus, the composition and proportion of stromal and immune cells in the TME may significantly influence therapeutic responses and clinical outcomes in cancer patients [ 7 , 8 ].…”

Identification and Validation of a Tumor Microenvironment-Related Gene Signature for Prognostic Prediction in Advanced-Stage Non-Small-Cell Lung Cancer

“…An accurate pathological stage is an important basis for selecting lung cancer treatment. Nevertheless, the complexity and heterogeneity of tumor immunosuppressive microenvironment led to discrepant immunotherapy effects among patients at the same pathologic stages [ 9 ]. For particular individuals, the survival benefits of immunotherapy are minimal and with side effects.…”