scholarly journals Remodeling chondroitin-6-sulfate-mediated immune exclusion enhances anti-PD-1 response in colorectal cancer with microsatellite stability

2021 ◽  
pp. canimm.CIR-21-0124-A.2021
Author(s):  
Qijing Wu ◽  
Qiong Huang ◽  
Yu Jiang ◽  
Fei Sun ◽  
Bishan Liang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Stability ◽  
Immune Exclusion

scholarly journals Potential Mechanism of Immune Evasion Associated with the Master Regulator ASCL2 in Microsatellite Stability in Colorectal Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Qian Yang ◽  
Guowei Huang ◽  
Liyan Li ◽  
Enmin Li ◽  
Liyan Xu
Keyword(s):  
Colorectal Cancer ◽  
Immune Evasion ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Novel Treatments ◽  
T Cell Infiltration ◽  
Immune Resistance ◽  
Unbiased Gene ◽  
Ifn Γ ◽  
Microsatellite Stability

Colorectal cancer (CRC) has two major subtypes, microsatellite instability (MSI) and microsatellite stability (MSS) based on the genomic instability. In this study, using computational programs, we identified 9 master transcription factors (TFs) based on epigenomic profiling in MSS CRC samples. Notably, unbiased gene set enrichment analysis (GSEA) showed that several master TFs were strongly associated with immune-related functions in TCGA MSS CRC tissues, such as interferon gamma (IFN-γ) and interferon alpha (IFN-α) responses. Focusing to the top candidate, ASCL2, we found that CD8+ T cell infiltration was low in ASCL2 overexpressed MSS CRC samples. Compared with other gastrointestinal (GI) cancers (gastric cancer, MSI CRC, and esophageal cancer), ASCL2 is specifically upregulated in MSS CRC. Moreover, we identified 28 candidate genes in IFN-γ and IFN-α response pathways which were negatively correlated with ASCL2. Together, these results link transcriptional dysregulation with the immune evasion in MSS CRC, which may advance the understanding of immune resistance and contribute to developing novel treatments of MSS CRC.

scholarly journals Mismatch Repair Proteins and Microsatellite Instability in Colorectal Carcinoma (MLH1, MSH2, MSH6 and PMS2): Histopathological and Immunohistochemical Study

2017 ◽  
Vol 5 (1) ◽  
pp. 9-13 ◽  
Author(s):  
Nour El Hoda S. Ismael ◽  
Samar A. El Sheikh ◽  
Suzan M. Talaat ◽  
Eman M. Salem
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Immunohistochemical Study ◽  
Survival Rates ◽  
Immunohistochemical Expression ◽  
Egyptian Patients ◽  
Mismatch Repair Proteins ◽  
Microsatellite Stability ◽  
Colorectal Cancer Patients

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide. Microsatellite instability (MSI) is detected in about 15% of all colorectal cancers. CRC with MSI has particular characteristics such as improved survival rates and better prognosis. They also have a distinct sensitivity to the action of chemotherapy.AIM: The aim of the study was to detect microsatellite instability in a cohort of colorectal cancer Egyptian patients using the immunohistochemical expression of mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2).MATERIAL AND METHODS: Cases were divided into Microsatellite stable (MSS), Microsatellite unstable low (MSI-L) and Microsatellite unstable high (MSI-H). This Microsatellite stability status was correlated with different clinicopathological parameters.RESULTS: There was a statistically significant correlation between the age of cases, tumor site & grade and the microsatellite stability status. There was no statistically significant correlation between the gender of patients, tumor subtype, stage, mucoid change, necrosis, tumor borders, lymphocytic response, lymphovascular emboli and the microsatellite stability status.CONCLUSION: Testing for MSI should be done for all colorectal cancer patients, especially those younger than 50 years old, right sided and high-grade CRCs.

scholarly journals Superpixel image segmentation of VISTA expression in colorectal cancer and its relationship to the tumoral microenvironment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dongling Wu ◽  
Sean Hacking ◽  
Taisia Vitkovski ◽  
Mansoor Nasim
Keyword(s):  
Colorectal Cancer ◽  
Image Segmentation ◽  
T Cell Activation ◽  
Cell Activation ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
The United States ◽  
Mutational Status ◽  
Microsatellite Stability

AbstractColorectal cancer (CRC) is the third most common cause of cancer related death in the United States (Jasperson et al. in Gastroenterology 138:2044–2058, 10.1053/j.gastro.2010.01.054, 2010). Many studies have explored prognostic factors in CRC. Today, much focus has been placed on the tumor microenvironment, including different immune cells and the extracellular matrix (ECM). The present study aims to evaluate the role of V-domain immunoglobulin suppressor of T cell activation (VISTA). We utilized QuPath for whole slides image analysis, performing superpixel image segmentation (SIS) on a 226 patient-cohort. High VISTA expression correlated with better disease-free survival (DFS), high tumor infiltrative lymphocyte, microsatellite instability, BRAF mutational status as well as lower tumor stage. High VISTA expression was also associated with mature stromal differentiation (SD). When cohorts were separated based on SD and MMR, only patients with immature SD and microsatellite stability were found to correlate VISTA expression with DFS. Considering raised VISTA expression is associated with improved survival, TILs, mature SD, and MMR in CRC; careful, well-designed clinical trials should be pursued which incorporate the underlying tumoral microenvironment.

scholarly journals Prognostic significance of macrosatellite instability in patients under 50 years of age suffering from colorectal cancer

2009 ◽  
Vol 62 (5-6) ◽  
pp. 217-223
Author(s):  
Atila Fenjvesi
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Prognostic Significance ◽  
Young Patients ◽  
Dna Mismatch ◽  
Significant Difference ◽  
Sporadic Cases ◽  
Microsatellite Stability ◽  
Better Than

Introduction Colorectal cancer (CRC) can arise through two distinct mutational pathways: microsatellite instability or chromosomal instability. High-frequency microsatellite instability (MSI) occurs in approximately 15 percent of sporadic cases of CRCs. Many studies have well established that MSI, the hallmark of defective DNA mismatch repair, is associated with prolonged survival of CRC patients compared with tumors that are microsatellite stable. CRCs in patients under 50 years of age are rare and represent about 5% of the total number of tumors. The aim of this study was to analyze the prognostic significance of MSI in CRC patients younger than 50 at the time of diagnosis. Material and methods 31 patients with CRC under 50 years of age were tested for the presence of MSI, and compared with 35 patients aged 50 or more at the time of diagnosis. CRC-specific survival five-year- follow-up period was analyzed in relation to MSI status. Results The frequency of MSI among the young patients was 35.48%, which was significantly higher than the rate of 11.43% noted in older patients with CRCs (p<0.042). This study revealed no difference in survival in patients with CRCs aged less than 50 compared with those over 50 years of age. The five-years survival of young CRCs patients with MSI 81.82%, was better than that of the patients with cancers with microsatellite stability, 60%, but there was no significant difference in statistics. Discussion and conclusion In our study there was no statistically detectable significant difference between tumor microsatellite status and survival in young patients, although we confirmed the previous observations that MSI is associated with better prognosis. We found that the pathological stage of CRC was an independent and powerful predictor of the clinical outcome.

scholarly journals The Emerging Role of Checkpoint Inhibition in Microsatellite Stable Colorectal Cancer

2019 ◽  
Vol 9 (1) ◽  
pp. 5 ◽  
Author(s):  
David Hermel ◽  
Darren Sigal
Keyword(s):  
Colorectal Cancer ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Current Data ◽  
Inhibitor Therapy ◽  
Immunomodulatory Agents ◽  
Checkpoint Inhibitor Therapy ◽  
Microsatellite Stability

Checkpoint inhibitor therapy has introduced a revolution in contemporary anticancer therapy. It has led to dramatic improvements in patient outcomes and has spawned tremendous research into novel immunomodulatory agents and combination therapy that has changed the trajectory of cancer care. However, clinical benefit in patients with colorectal cancer has been generally limited to tumors with loss of mismatch repair function and those with specific germline mutations in the DNA polymerase gene. Unfortunately, tumors with these specific mutator phenotypes are in the minority. Recent pre-clinical and clinical studies have begun to reveal encouraging results suggesting that checkpoint inhibitor therapy can be expanded to an increasing number of colorectal tumors with microsatellite stability and the absence of traditional predictive biomarkers of checkpoint inhibitor response. These studies generally rely on combinations of checkpoint inhibitors with chemotherapy, molecular targeted therapy, radiation therapy, or other novel immunomodulatory agents. This article will review the most current data in microsatellite stable colorectal cancer.

scholarly journals Epithelial-Mesenchymal Transition and Somatic Alteration in Colorectal Cancer with and without Peritoneal Carcinomatosis

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Y. A. Shelygin ◽  
N. I. Pospekhova ◽  
V. P. Shubin ◽  
V. N. Kashnikov ◽  
S. A. Frolov ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Peritoneal Carcinomatosis ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Potential ◽  
Mesenchymal Transition ◽  
Low Degree ◽  
Epithelial Phenotype ◽  
Somatic Alterations ◽  
Microsatellite Stability ◽  
Degree Of Differentiation

Colorectal cancer is highly metastatic even when the tumors are small. To disseminate, cells use a complex and multistage process known as the epithelial-mesenchymal transition, in which epithelial phenotype is transformed into mesenchymal phenotype. The objective of this study is to describe the epithelial-mesenchymal transition in terms of gene expression profile and somatic alterations in samples of colorectal cancer with or without peritoneal carcinomatosis. We analyzed samples taken from 38 patients with colorectal cancer (stages II-IV) and samples from 20 patients with colorectal cancer complicated by peritoneal carcinomatosis. The expression ofZEB1, ZEB2, CDH1, VIM, andSNAI1was analyzed by real-time PCR.KRAS/BRAFmutations were mapped using sequencing. Microsatellite instability was evaluated by fragment analysis. Epithelial-mesenchymal transition was detected in 6 out of 38 samples of colorectal cancer (stages II-IV), 7 out of 20 tumors from patients with peritoneal carcinomatosis, and 19 out of 20 samples taken from carcinomatous nodules. Tumors of the mesenchymal subtype displayed high frequency of somatic mutations, microsatellite stability, and low degree of differentiation. The identification of epithelial-mesenchymal transition may be used as a marker of high metastatic potential, which is particularly relevant at early stages of tumor growth.

Sign in / Sign up

Export Citation Format

Share Document