Analysis of Tumor-Infiltrating T-Cell Transcriptomes Reveal a Unique Genetic Signature across Different Types of Cancer

Abstract

CD8+ and CD4+ T-cells play a key role in cellular immune responses against cancer by cytotoxic responses and effector lineages differentiation, respectively. These subsets have been found in different types of cancer; however, it is unclear whether tumor-infiltrating T-cell subsets exhibit similar transcriptome profiling across different types of cancer in comparison with healthy tissue-resident T-cells. Thus, we analyzed the single cell transcriptome of five tumor-infiltrating CD4-T, CD8-T and Treg cells obtained from different types of cancer to identify specific pathways for each subset in malignant environments. An in silico analysis was performed from single-cell RNA-sequencing data available in public repositories (Gene Expression Omnibus) including breast cancer, melanoma, colorectal cancer, lung cancer and head and neck cancer. After dimensionality reduction, clustering and selection of the different subpopulations from malignant and nonmalignant datasets, common genes across different types of cancer were identified and compared to nonmalignant genes for each T-cell subset to identify specific pathways. Exclusive pathways in CD4+ cells, CD8+ cells and Tregs, and common pathways for the tumor-infiltrating T-cell subsets were identified. Finally, the identified pathways were compared with RNAseq and proteomic data obtained from T-cell subsets cultured under malignant environments and we observed that cytokine signaling, especially Th2-type cytokine, was the top overrepresented pathway in Tregs from malignant samples.