Immune profiling of the macroenvironment in colorectal cancer unveils systemic dysfunction and plasticity of immune cells.

Background: Tumour immune macroenvironment is comprised of tumour and surrounding organs responding to tumourigenesis and immunotherapy. The lack of comprehensive analytical methods hinders its application for prediction of survival and treatment response in colorectal cancer (CRC) patients.

Methods: Cytometry by time-of-flight (CyTOF) and RNA-seq was applied to characterise immune cell heterogeneity in a discovery cohort including tumour, blood and intestinal architecture comprising epithelium, lamina propria, submucosa, muscularis propria of normal bowel and tumour-adjacent bowel tissues.

PDP1 promotes KRAS mutant colorectal cancer progression by serving as a scaffold for BRAF and MEK1.

The oncogenic role of KRAS in colorectal cancer (CRC) progression is well-established. Despite this, identifying effective therapeutic targets for KRAS-mutated CRC remains a significant challenge. This study identifies pyruvate dehydrogenase phosphatase catalytic subunit 1 (PDP1) as a previously unrecognized yet crucial regulator in the progression of KRAS mutant CRC.

Biomarkers of Pathologic Complete Response to Neoadjuvant Immunotherapy in Mismatch Repair-Deficient Colorectal Cancer.

Purpose: Immune checkpoint inhibitors (ICI) have become the standard of care for patients with mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) colorectal cancer. However, biomarkers of response to ICI are still lacking.

Experimental Design: Forty-two patients with dMMR colorectal cancer treated with neoadjuvant PD-1 blockade were prospectively enrolled.

Dynamic heterogeneity of colorectal cancer during progression revealed clinical risk-associated cell types and regulations in single-cell resolution and spatial context.

Background: Tumor heterogeneity is contributed by tumor cells and the microenvironment. Dynamics of tumor heterogeneity during colorectal cancer (CRC) progression have not been elucidated.

Methods: Eight single-cell RNA sequencing (scRNA-seq) data sets of CRC were included.

MAP7D2 reduces CD8 cytotoxic T lymphocyte infiltration through MYH9-HMGB1 axis in colorectal cancer.

Immune checkpoint inhibitors (ICIs) represent a new paradigm in cancer immunotherapy, but can be largely restricted by the limited presence of CD8 cytotoxic T lymphocytes (CTLs) in colorectal cancer (CRC) patients with microsatellite stable (MSS) tumors. Here, through next-generation sequencing, we identify microtubule-associated protein 7 domain 2 (MAP7D2) as an exploitable therapeutic maneuver to improve the efficacy of ICIs for MSS CRC therapy. In human CRC tissues, MAP7D2 expression is significantly increased in MSS CRC, and MAP7D2 adversely correlates with the presence of antitumor T lymphocytes.

LncRNA DANCR represses Doxorubicin-induced apoptosis through stabilizing MALAT1 expression in colorectal cancer cells.

Long non-coding RNA (lncRNA) DANCR has been reported to participate in key processes such as stem cell differentiation and tumorigenesis. In a high throughput screening for lncRNAs involved in Doxorubicin-induced apoptosis, we found DANCR was suppressed by Doxorubicin and it acted as an important repressor of apoptosis in colorectal cancer. Further studies demonstrated that DANCR promoted the oncogenic lncRNA MALAT1 expression via enhancing the RNA stability of MALAT1 to suppress apoptosis.

Continent Ileostomy as an Alternative to End Ileostomy.

Continent ileostomy (CI) was once a prevalent surgical technique for patients who required total proctocolectomy but then gave way to ileal pouch-anal anastomosis (IPAA) after 1980. Although IPAA has been the gold standard procedure preferred by most patients when total proctocolectomy is required, due to its imitation of physiological function of rectum and preserved function of anus, various complications have been observed with a relatively high rate of morbidity that could affect pouch longevity. Once serious complications such as pelvic abscesses and/or fistula occur, the pouch often needs to be removed.