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Prognostic value of immune scores in the microenvironment of colorectal cancer.

ABSTRACT: Cancer immunotherapy has become an important means of cancer treatment; however, the complex composition and heterogeneity of the colorectal cancer (CRC) microenvironment pose a huge challenge to cancer immunotherapy. Using data downloaded from The Cancer Genome Atlas database, the differences in the microenvironment between cases with low and high immune scores were examined at the multiomics level using bioinformatics approaches. It was revealed that the samples with high immune scores had good cytolytic immune responses and relatively abundant stromal cells, as well as significant infiltration of 22 immune cell subsets and a high non-synonymous mutation burden and neoantigen burden. All of these characteristics contribute to a good prognosis. To better understand the impact of immune-related genes on prognosis, differentially expressed genes between the low and high immune score samples were identified and it was concluded that serpin family Emember 1 (SERPINE1) and ubiquitin C-terminal hydrolase L1 (UCHL1) may be potential therapeutic targets. The relationship between the immune score and the infiltration of 22 immune cells and the difference in SERPINE1 expression were verified by analyzing the GSE17536 and GSE21510 data sets downloaded from the Gene Expression Omnibus database. The present study analyzed the unique properties of immune cells in the CRC microenvironment, which are of great significance for understanding CRC immune mechanism and may also provide novel ideas for the targeted design of cancer immunotherapy.

SUBMITTER: Yuan W

PROVIDER: S-EPMC7509622 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Prognostic value of immune scores in the microenvironment of colorectal cancer.

Yuan Wenliang W Cai Wei W Huang Xiao X Peng Sihua S

Oncology letters 20200918 5

Cancer immunotherapy has become an important means of cancer treatment; however, the complex composition and heterogeneity of the colorectal cancer (CRC) microenvironment pose a huge challenge to cancer immunotherapy. Using data downloaded from The Cancer Genome Atlas database, the differences in the microenvironment between cases with low and high immune scores were examined at the multiomics level using bioinformatics approaches. It was revealed that the samples with high immune scores had goo ...[more]

PMID: 32994819

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Project description:IntroductionCancer progression is determined not only by the malignant behavior of tumors but also by the immune microenvironment. The tumor immune microenvironment also plays a pivotal role in determining the clinical response of non-small-cell lung cancer (NSCLC) to immunotherapies. To understand the possible mechanisms and explore new targets in lung cancer immunotherapy, we characterized the immune profiles in NSCLC patients.MethodsSeventy-one NSCLC patients who underwent radical resection were selected. The immune cell composition in paired tumor and adjacent normal lung tissues was tested by flow cytometry. The associations of tumor immune microenvironment characteristics with clinicopathological factors and overall survival were analyzed. Kaplan-Meier curves and Cox proportional hazards models were used to determine differences in survival.ResultsCompared with adjacent normal lung tissues, an increased proportion of CD45+ hematopoietic-derived cells, CD4+ T cell subtypes, Tregs and B cells was observed in tumor samples with a reduced frequency of myeloid cell populations. There was no significant increase in total CD8+ T cells, but both PD1+ and CD38+ CD8+ T cells were significantly enriched in tumor samples and statistically significantly associated with tumor size. In addition, positive CD38 expression was highly correlated with PD1 positivity. A high proportion of CD8+ T cells and a low percentage of PD1+ CD8+ T cells were statistically significantly associated with better survival in stage II and III patients, whereas a low frequency of CD38+ CD8+ T cells was statistically significantly associated with better survival in all patients and identified as an independent prognostic factor (p=0.049).ConclusionWe profiled the immune cells in the tumor tissues of NSCLC patients using flow cytometry. The results revealed significant enrichment of infiltrating immune cells. A strong correlation was identified between CD38 and PD-1 expression on CD8+ T cells in tumors. CD8+ T cells and their subtypes play a critical role in the prediction of prognosis.

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Project description:Colorectal cancer (CRC) ranks as the second leading cause of cancer-related mortality globally and is the third most prevalent cancer. The effective treatment of CRC is challenged by tumor drug resistance, underscoring the urgent need for novel therapeutic strategies. It is well recognized that epigenetic modifications, particularly DNA methylation, significantly contribute to the initiation and advancement of CRC. Tumors frequently exhibit hypermethylation of specific gene promoters alongside a general hypomethylation of genomic DNA. In normal tissues, gene promoters, particularly those of tumor suppressor genes, are typically unmethylated, whereas they are often hypermethylated in cancerous tissues. Previous studies have identified the methylation status of the CpG island within the SLC30A10 gene as a reliable biomarker for CRC. Notably, a hypermethylated phenotype is inversely correlated with SLC30A10 expression. However, the precise functional implications of SLC30A10 suppression in the context of CRC progression remain to be elucidated.). The investigation of molecular pathways involved in metal metabolism in CRC has not been conducted previously at the transcriptomic level. Furthermore, the relationship between the mutational characteristics of tumors—such as individual mutations, mutational burden, and microsatellite instability—and the activity of genes related to metal metabolic pathways has not been explored. This project aims to be the first to examine the antitumor potential of modulating the transport systems for manganese and zinc ions in CRC. The molecular function of SLC30A10 is to export zinc (Zn) and manganese (Mn) ions from the cell. Additionally, SLC30A10 plays a crucial role in mitigating Mn-induced cytotoxicity and facilitates Zn transport to early endosomes while promoting endosomal recirculation to avert Zn toxicity. Our findings indicate that overexpression of SLC30A10 is correlated with the knockout of its functional antagonist, SLC39A14 in the HuTu80 and HCT-15 cell lines.

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Prognostic value of immune scores in the microenvironment of colorectal cancer.

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Prognostic value of immune scores in the microenvironment of colorectal cancer.

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