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How the Tumor Micromilieu Modulates the Recruitment and Activation of Colorectal Cancer-Infiltrating Lymphocytes

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Luciana Gneo et al.

Summary: Monocytic myeloid-derived suppressor cells (M-MDSCs) are expanded in colorectal cancer (CRC) patients, inhibiting T cell proliferation. Blocking IL-10 released by HLA-DR- cells abrogates the suppressive function of M-MDSCs. Tumour conditioned media (TCM) reduces HLA-DR expression, increases IL-10 release, and promotes monocyte suppressive activity. TGF-beta in TCM drives monocyte immunosuppressivity and is enriched at the invasive margin of CRC.

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Summary: This study aimed to identify TME-related hub genes and prognostic biomarkers in colorectal adenoma (CRAD). The results showed that CX3CR1 played a crucial role in immune cell infiltration and macrophage polarization, and may serve as a prognostic biomarker in colorectal cancer (CRC).

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Ketogenesis Attenuates KLF5-Dependent Production of CXCL12 to Overcome the Immunosuppressive Tumor Microenvironment in Colorectal Cancer

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Summary: This study identifies ketogenesis as a critical regulator of the tumor microenvironment in colorectal cancer and suggests the potential for ketogenic diets as a metabolic strategy to overcome immunosuppression and prolong survival.

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Md Sanower Hossain et al.

Summary: Colorectal cancer (CRC) is a highly lethal disease with increasing incidence and mortality worldwide. Early detection and treatment are essential for survival, but recurrence and drug resistance pose significant challenges. This comprehensive review addresses the development, risk factors, and management strategies of CRC. In addition, natural products as potential therapeutics are also discussed. Public awareness is crucial for improving CRC management, especially in developing countries where access to diagnosis and treatment resources is limited.

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Comparison of Immune Response Assessment in Colon Cancer by Immunoscore (Automated Digital Pathology) and Pathologist Visual Scoring

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Summary: The immune response in colon cancer patients varies greatly and has clinical relevance. Comparing Immunoscore (IS) and pathologist visual scoring, this study found low agreement among pathologists and weak concordance between the two methods. The heterogeneity of immune infiltrate leads to inconsistent interpretation among pathologists, making non-standardized methods unlikely to replicate IS results. Introducing immune response as a biomarker for colon cancer prognosis improves prediction accuracy, and the standardized IS assay outperforms expert pathologist assessment in the clinical setting.

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PU.1-driven Th9 Cells Promote Colorectal Cancer in Experimental Colitis Models Through Il-6 Effects in Intestinal Epithelial Cells

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Summary: This study identified expanded IL-9 and PU.1-expressing mucosal Th9 cells in colorectal cancer patients, with especially high levels in patients with colitis-associated neoplasias. IL-9 and PU.1 promoted tumor growth in vivo, while GATA3 inactivation did not affect Th9-mediated tumor growth. IL-9 regulated tumor growth by controlling claudin2/3 expression and IL-6 production by T cells in colorectal tumors.

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Lucas A. Horn et al.

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Histone methyltransferase WHSC1 loss dampens MHC-I antigen presentation pathway to impair IFN-γ stimulated antitumor immunity

Jiale Ren et al.

Summary: IFN-gamma signaling has opposing effects on tumor immunity, stimulating MHC-I antigen presentation while enhancing the PD-L1 checkpoint pathway. This study shows that the loss of a histone dimethyltransferase called WHSC1 impairs the antitumor effect of IFN-gamma signaling by downregulating MHC-I expression. WHSC1 promotes MHC-I gene expression through its interaction with NLRC5, and its expression is correlated with enhanced MHC-I expression and favorable disease outcomes in colorectal cancer.

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Utilizing chemokines in cancer immunotherapy

Florian Markl et al.

Summary: This review discusses the pleiotropic functions of chemokines in the tumor microenvironment and strategies of utilizing chemokines or chemokine antagonism in immunotherapy to improve treatment efficacy.

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Pengzhao Shang et al.

Summary: A novel anti-VEGFR2-IFN alpha mutant protein was designed in this study to target VEGFR2, demonstrating specific inhibition of tumor cell proliferation, promotion of apoptosis, and suppression of migration and invasion of colorectal cancer cells through the PI3K-AKT-GSK3 beta-snail signaling pathway. This mutant protein also showed superior anti-tumor efficacy by enhancing dendritic cell maturation, activity, and increasing tumor-infiltrating CD8(+) T cells in the tumor microenvironment, providing a potential new approach to cancer immunotherapy.

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Prognostic Immune-Related Analysis Based on Differentially Expressed Genes in Left- and Right-Sided Colon Adenocarcinoma

Jun-Nan Guo et al.

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Inflammatory Mediators and Gut Microbial Toxins Drive Colon Tumorigenesis by IL-23 Dependent Mechanism

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Summary: The Western-style diet high in fat is a major cause of obesity and increased risk of colon cancer, with inflammatory molecules playing a key role in the connection between obesity and colon tumorigenesis. IL-23 is significant in the impact of a Western-style diet on obesity, gut microbiome, and colon tumorigenesis, suggesting it as a potential target for prevention and treatment. Pro-inflammatory eicosanoids and gut bacterial toxins facilitate IL-23 production, which is crucial in the progression of obesity-associated colon tumors.

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Integrin β7 Inhibits Colorectal Cancer Pathogenesis via Maintaining Antitumor Immunity

Youhua Zhang et al.

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Kewei Liu et al.

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IL-6 programs TH-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways

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High-level expression of chemokine CXCL16 by tumor cells correlates with a good prognosis and increased tumor-infiltrating lymphocytes in colorectal cancer

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Chemokine receptor CCR6 expression level and liver metastases in colorectal cancer

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Augmentation of effector CD8+ T cell generation with enhanced granzyme B expression by IL-27

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Semliki forest virus vectors engineered to express higher IL-12 levels induce efficient elimination of murine colon adenocarcinomas

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Expression of IL-27 in murine carcinoma cells produces antitumor effects and induces protective immunity in inoculated host animals

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CD4+CD25+ regulatory lymphocytes induce regression of intestinal tumors in ApcMin/+ mice

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Chemokine receptor CXCR4 expression in colorectal cancer patients increases the risk for recurrence and for poor survival

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