Description: The tumor immune microenvironment is a complex ecosystem formed by many distinct and interacting cell populations, and its composition may be closely related to cancer initiation, prognosis, and response to clinical treatment. Here, we performed single-cell RNA sequencing (scRNA-seq) on 5,345 multi-region immune cells isolated from 8 treatment naïve colorectal carcinoma (CRC) patients, in which distinct immune cell subsets, including T cells, B cells, myeloid cells, and mast cells were characterized. We observed extensive changes in the proportion and functional states of T cells and B cells in tumor tissues compared to those of paired normal tissues as well as of liver metastasis. In particular, we found that naïve T cells and lgA secreting plasma cells were reduced whereas cytotoxic T cells, CD4+ T cells, and lgG producing plasma cells were enriched in the CRC microenvironment. Interestingly, our results indicated that the gene for a cytolytic molecule, GZMA, was highly expressed in T cells derived from early CRC tumors and up-regulated GZMA in colon adenocarcinoma (from TCGA COAD) was associated with longer progression-free survival (PFS) (P = 0.036), indicating that impairment of the T cell meditated immune response and enrichment of mast cells could be a major factor for poor CRC prognosis. A subset of B cells with higher expression of IgA features was shown to be associated with poor prognosis, which may be functionally important in cancer immunity. Importantly, differential expression analysis indicated that B cells from early CRC tumor were characterized as pre-B like with anti-tumor capabilities, while B cells from advanced CRC tumors tended to be developed into plasma cells. By parsing the unique classes and subclasses, functions and interactions of immune cells within CRC tumors and adjacent non-tumor tissue; identifying the association of IgA+IGLC2+ plasma cells with poor CRC prognosis; and demonstrating a significant interaction between myeloid cells and cytotoxic T cells in advanced CRC tumors, our results provide a deeper insight into the immune infiltration within CRC and will aid in the rational design of immunotherapies against cancer.

Data type: Raw sequence reads; Transcriptome or Gene expression

Sample scope: Multiisolate

Relevance: Other

Release date: 2020-05-21

Last updated: 2020-02-21

Data size: 19.82TB