Immune overdrive signature in colorectal tumor subset predicts poor clinical outcome

The prognostic value of immune cell infiltration within the tumor microenvironment (TME) has been extensively investigated via histological and genomic approaches. Based on the positive prognostic value of T cell infiltration, Immunoscore has been developed and validated for predicting risk of recurrence for colorectal cancer (CRC). Also, association between a consensus T helper 1 (Th-1) immune response and favorable clinical outcomes has been observed across multiple cancer types. Here, we reanalyzed public genomic data sets from The Cancer Genome Atlas (TCGA) and NCBI Gene Expression Omnibus (NCBI-GEO) and performed multispectral immunohistochemistry (IHC) on a cohort of colorectal tumors. We identified and characterized a risk group, representing approximately 10% of CRC patients, with high intratumoral CD8+ T cell infiltration, but poor prognosis. These tumors included both microsatellite instable (MSI) and stable (MSS) phenotypes and had a high density of tumor-associated macrophages (TAMs) that expressed CD274 (programmed death-ligand 1 [PD-L1]), TGF-β activation, and an immune overdrive signature characterized by the overexpression of immune response and checkpoint genes. Our findings illustrate that CRC patients may have poor prognosis despite high CD8+ T cell infiltration and provide CD274 as a simple biomarker for identifying these patients.
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research

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The sequence of events leading to the development of colorectal cancer, currently the third most common malignancy in Western countries, is effectively disrupted by the resection of its precursor lesions. Colonoscopy is the mainstay in lesion detection, and endoscopic polypectomy is the conventional therapeutic response for the overwhelming majority of identified polyps. Approximately 2% of lesions are larger (>20  mm) and are laterally spreading lesions (LSLs). EMR is considered the standard of care for the majority of these because it has been proved to be safer, less resource-intensive, and less expensive than surgery.
Source: Gastrointestinal Endoscopy - Category: Gastroenterology Authors: Tags: Original article Source Type: research
Authors: Zeng X, Liu Q, Yang Y, Jia W, Li S, He D, Ma R Abstract Placenta-specific protein 8 (PLAC8) is a conserved protein with a molecular weight of 12.5 kDa. The specific function of this protein has not been fully elucidated, however, PLAC8 has been found to play an important tumor regulatory role in certain types of cancer, including colon, pancreatic and liver cancer. PLAC8 also participates in the regulation of the cell cycle, autophagy, epithelial-mesenchymal transition and other cellular functions, indicating its potential as a molecular target worth further investigation. The present study investigated th...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Authors: Nomura M, Takahashi H, Fujii M, Miyoshi N, Haraguchi N, Hata T, Matsuda C, Yamamoto H, Mizushima T, Mori M, Doki Y Abstract The T3 subdivision has been reported to predict prognosis in rectal cancer. However, few studies describe a correlation between T3 subdivision and prognosis in colon cancer. The current study aimed validate the correlation between the invasion distance (ID) beyond the muscularis propria and prognosis in colorectal cancer. The present retrospective study included 148 consecutive patients with pathologically confirmed T3 colorectal cancer, who underwent resection between January 2008 an...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Authors: Wang Y, Zhang B, Gao G, Zhang Y, Xia Q Abstract Guanine nucleotide exchange factor T (GEFT), a member of the Rho guanine nucleotide exchange factor family, is expressed in a variety of tumors. In the present study, the expression and clinical significance of GEFT in malignant digestive tract tumors was assessed. Tumor and adjacent control samples from 180 patients were tested. Positive GEFT expression rates were 80, 83.33 and 86.67% in esophageal squamous carcinoma (ESCC), gastric carcinoma (GC) and colorectal cancer (CRC), respectively. GEFT expression was associated with diffuse type carcinoma according ...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
To investigate the synergistic antitumour effect of Clostridium butyricum combined with apatinib on colorectal cancer in mice. Murine colorectal carcinoma cell line CT26.WT cells were xenografted into the skin of BALB/c mice. Tumour-bearing mice were randomly divided into four groups, and given different treatment options (PBS control; C. butyricum; apatinib; C. butyricum + apatinib). Real-time PCR was used to detect C. butyricum content in the intestine of mice given C. butyricum. The effects of various regimens on tumour growth were monitored, and CD31, proliferating cell nuclear antigen (PCNA), Bcl-2 and cleaved caspase...
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research
Publication date: Available online 16 October 2019Source: Life SciencesAuthor(s): Ahmed Hammad, Zhao-Hong Zheng, Yang Gao, Akhileshwar Namani, Hong-Fei Shi, Xiuwen TangAbstractAimsColorectal cancer (CRC) is the third most common cancer worldwide. Nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of many cytoprotective genes, plays a protective role in carcinogenesis. Recent studies have identified a specific gene-expression signature regulated by the Nrf2 pathway in lung adenocarcinoma and head-and-neck squamous cell cancer. However, the roles of Nrf2 in the development of colitis-associated colorectal...
Source: Life Sciences - Category: Biology Source Type: research
Publication date: Available online 17 October 2019Source: Urology Case ReportsAuthor(s): Amer Amin, Alexandar Blazevski, Matthijs Scheltema, Phillip StrickerAbstractA 75-year-old man with a background history of total colectomy (including the distal rectum anal canal), has a suspicion of prostate cancer based on an elevated PSA and high risk features on multiparametric MRI. Here we describe the case in detail including the technique utilized to obtain prostate biopsy cores.
Source: Urology Case Reports - Category: Urology & Nephrology Source Type: research
ConclusionsExcellent outcomes are possible for curative intent recurrent colon cancer surgery. The site of loco-regional recurrence plays a significant role in outcomes.Table of Contents Summary: Colon cancer recurrence can be treated surgically with optimal outcomes. Anastomotic recurrence is associated with improved survival.
Source: The American Journal of Surgery - Category: Surgery Source Type: research
ConclusionThe fluorescent marking clips were easily placed and recognized with a fluorescent laparoscope. This method is expected to be safe and risks of accidental puncture related to tattoo marking method can be reduced or almost eliminated.
Source: International Journal of Surgery Case Reports - Category: Surgery Source Type: research
Creatine, the organic acid that is popularly taken as a supplement by athletes and bodybuilders, serves as a molecular battery for immune cells by storing and distributing energy to power their fight against cancer, according to new UCLA research.The study, conducted in mice and published in the Journal of Experimental Medicine, is the first to show that creatine uptake is critical to the anti-tumor activities of CD8 T cells, also known as killer T cells, the foot soldiers of the immune system. The researchers also found that creatine supplementation can improve the efficacy of existing immunotherapies.“Because oral ...
Source: UCLA Newsroom: Health Sciences - Category: Universities & Medical Training Source Type: news
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