Abstract
Recent, large-scale expression–based subtyping has advanced our understanding of the genomic landscape of colorectal cancer (CRC) and resulted in a consensus molecular classification that enables the categorization of most CRC tumors into one of four consensus molecular subtypes (CMS). Currently, major progress in characterization of immune landscape of tumor-associated microenvironment has been made especially with respect to microsatellite status of CRCs. While these studies profoundly improved the understanding of molecular and immunological profile of CRCs heterogeneity less is known about repertoire of the tumor infiltrating immune cells of each CMS.In order to comprehensively characterize the immune landscape of CRC we re-analyzed a total of 15 CRC genome-wide expression data sets encompassing 1597 tumors and 125 normal adjacent colon tissues. After quality filtering, CRC clusters were discovered using a combination of multiple clustering algorithms and multiple validity metrics. CIBERSORT algorithm was used to compute relative proportions of 22 human leukocyte subpopulations across CRC clusters and normal colon tissue. Subsequently, differential expression specific to tumor epithelial cells was calculated to characterize mechanisms of tumor escape from immune surveillance occurring in particular CRC clusters.Our results not only characterize the common and cluster-specific influx of immune cells into CRCs but also identify several deregulated gene targets that may contribute to improvement of immunotherapeutic strategies in CRC.
Highlights
The Cancer Genome Atlas (TCGA) and other large-scale cancer molecular profiling efforts showed that colorectal cancer (CRC) is a heterogeneous disease, arising from a number of possible etiological pathways that are responsible for driving CRC development [1]
We placed the immune-tumor interface into a CRC consensus molecular subtype context. This led to the identification of common and cluster-specific properties of immune landscape as well as immune escape mechanisms
We observed a common decrease of plasma cells, macrophages M2 and CD8+ T lymphocytes (CTLs)
Summary
The Cancer Genome Atlas (TCGA) and other large-scale cancer molecular profiling efforts showed that colorectal cancer (CRC) is a heterogeneous disease, arising from a number of possible etiological pathways that are responsible for driving CRC development [1]. Recent integration of various CRC gene expressionbased subtypings resulted in a consensus molecular CRC classification that enables the segregation of most tumors into one of four consensus molecular subtypes (CMS) [2]. Each of CRC CMS has been marked by distinct driver mutations and genetic or epigenetic signatures that include microsatellite instability (MSI), CpG island methylator phenotype (CIMP), chromosomal instability (CIN) and diverse spectrum of pathway activation (for details see Dienstmann et al [3]). A gene-set enrichment analysis of gene expression data has provided initial insight into immune microenvironment CMS groups [3, 4]. It has been demonstrated that CMS1 tumors are characterized by high infiltration of immune cells associated with adaptive immunity. CMS4 displays so called “inflamed phenotype” associated with expansion of innate immunity cells and expression of immunosuppressive factors [3].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
