Analysis of the gene regulatory program of tumor infiltrating lymphocytes

The adaptive immune responses are started by the activation of naïve T cells that, upon recognition of an antigen, proliferate, differentiate and generate functionally different cellular subsets. This process is accompanied by a progressive loss of plasticity determined by the context and the type of antigen stimulation received. Indeed, T cells maturation occurs after several cycles of proliferation and changes of the gene expression programs towards the effector, exhausted or memory phenotypes depending on the environment stimuli. However, all the mechanisms underlying these processes are not fully understood. In order to elucidate the function and heterogeneity of T cells during the immune response against cancer, we have analyzed the tumor infiltrating lymphocytes in a mouse model of colon cancer, by using single-cell RNA-seq analysis. Performing gene set enrichment analysis, we have identified distinct subsets of T lymphocytes, each of them characterized by a peculiar gene signatures. The study reveals a differential expression of different epigenetic factors among the T cell subsets. For the future, the aim is to focus our attention on the distinct clusters to directly evaluate the role of different epigenetic factors by CRISPR-Cas9 gene editing. To conclude, this work can be considered as the first step needed to identify the epigenetic factors and pathways involved in the differentiation of different T cell subsets in the context of cancer.