HLA Class I Loss in Colorectal Cancer: Implications for Immune Escape and Immunotherapy

Investigators summarize the prevalence and molecular mechanisms behind HLA-I loss in colorectal cancer (CRC), and discuss HLA-I expression/loss in the context of the newly identified CRC molecular subtypes.
[Cellular & Molecular Immunology]
Anderson, P., Aptsiauri, N., Ruiz-Cabello, F., & Garrido, F. (2021). HLA class I loss in colorectal cancer: implications for immune escape and immunotherapy. Cellular & Molecular Immunology, 1–10. https://doi.org/10.1038/s41423-021-00634-7 Cite
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Epithelium-Derived Indian Hedgehog Restricts Stromal Expression of ErbB Family Members That Drive Colonic Tumor Cell Proliferation

Scientists found that recombinant EREG, BTC, and NRG1 but not Lgr5 ligand R-Spondin promoted growth and proliferation of Apc double mutant colonic organoids.
[Oncogene]
Westendorp, F., Karpus, O. N., Koelink, P. J., Vermeulen, J. L. M., Meisner, S., Koster, J., Büller, N. V. J. A., Wildenberg, M. E., Muncan, V., & van den Brink, G. R. (2021). Epithelium-derived Indian Hedgehog restricts stromal expression of ErbB family members that drive colonic tumor cell proliferation. Oncogene, 1–16. https://doi.org/10.1038/s41388-020-01633-0 Cite
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Histone Methyltransferase WHSC1 Inhibits Colorectal Cancer Cell Apoptosis via Targeting Anti-Apoptotic BCL2

Scientists revealed how WHSC1 regulates tumorigenesis and chemosensitivity of colorectal cancer.
[Cell Death Discovery]
Wang, Y., Zhu, L., Guo, M., Sun, G., Zhou, K., Pang, W., Cao, D., Tang, X., & Meng, X. (2021). Histone methyltransferase WHSC1 inhibits colorectal cancer cell apoptosis via targeting anti-apoptotic BCL2. Cell Death Discovery, 7(1), 1–9. https://doi.org/10.1038/s41420-021-00402-6 Cite
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Targeting the m6A-Reader Protein YTHDF1 Effectively Re-Sensitizes Cisplatin Resistant Colon Cancer Cells through Modulating the Glutaminase (GLS)-Mediated Glutamine Metabolism

Researchers report YTHDF1 was significantly upregulated in human colon tumors and cell lines. Overexpression of YTHDF1 decreased the cisplatin sensitivity of colon cancer cells.
[Molecular Therapy-Oncolytics]
Chen, P., Liu, X., Lin, X., Gao, L., Zhang, S., & Huang, X. (2021). Targeting the m6A-reader Protein YTHDF1 Effectively Re-Sensitizes Cisplatin Resistant Colon Cancer Cells through Modulating the Glutaminase (GLS)-Mediated Glutamine Metabolism. Molecular Therapy - Oncolytics, 0(0). https://doi.org/10.1016/j.omto.2021.01.001 Cite
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Semiconducting Polymer Nanoparticles for Photothermal Ablation of Colorectal Cancer Organoids

Tumor organoid technology was used to evaluate the ablative potential of CD44-targeted polymer nanoparticles using hyaluronic acid (HA) as the targeting agent and coating it onto hybrid donor acceptor polymer particles (HDAPPs) to form HA-HDAPPs.
[Scientific Reports]
McCarthy, B., Cudykier, A., Singh, R., Levi-Polyachenko, N., & Soker, S. (2021). Semiconducting polymer nanoparticles for photothermal ablation of colorectal cancer organoids. Scientific Reports, 11(1), 1532. https://doi.org/10.1038/s41598-021-81122-w Cite
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Eubacterium rectale Contributes to Colorectal Cancer Initiation via Promoting Colitis

Scientists showed that E. rectale endotoxin activated the transcription factor NF-κΒ, which regulated multiple aspects of innate and adaptive immune responses in normal colon epithelial cells.
[Gut Pathogens]
Wang, Y., Wan, X., Wu, X., Zhang, C., Liu, J., & Hou, S. (2021). Eubacterium rectale contributes to colorectal cancer initiation via promoting colitis. Gut Pathogens, 13(1), 2. https://doi.org/10.1186/s13099-020-00396-z Cite
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The Role of the Hippo Pathway in the Pathogenesis of Inflammatory Bowel Disease

The authors summarize the latest scientific literature on the involvement of this pathway in inflammatory bowel disease (IBD) from the following perspectives that account for the IBD pathogenesis: intestinal epithelial cell regeneration, immune regulation, gut microbiota, and angiogenesis.
[Cell Death & Disease]
Xie, Z., Wang, Y., Yang, G., Han, J., Zhu, L., Li, L., & Zhang, S. (2021). The role of the Hippo pathway in the pathogenesis of inflammatory bowel disease. Cell Death & Disease, 12(1), 1–14. https://doi.org/10.1038/s41419-021-03395-3 Cite
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Reprogramming Immunosuppressive Myeloid Cells by Activated T Cells Promotes the Response to Anti-PD-1 Therapy in Colorectal Cancer

The levels of infiltrating myeloid-derived suppressor cells (MDSCs) were significantly higher in the non-responding organoids and were selectively reduced in the responding group, with MDSCs showing increased apoptosis and attenuated functional activity after anti-PD-1 treatment.
[Signal Transduction and Targeted Therapy]
Chen, J., Sun, H.-W., Yang, Y.-Y., Chen, H.-T., Yu, X.-J., Wu, W.-C., Xu, Y.-T., Jin, L.-L., Wu, X.-J., Xu, J., & Zheng, L. (2021). Reprogramming immunosuppressive myeloid cells by activated T cells promotes the response to anti-PD-1 therapy in colorectal cancer. Signal Transduction and Targeted Therapy, 6(1), 1–14. https://doi.org/10.1038/s41392-020-00377-3 Cite
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The Amino Acid Transporter SLC7A5 Is Required for Efficient Growth of KRAS-Mutant Colorectal Cancer

The authors showed that concomitant mutation of Apc and Kras in the mouse intestinal epithelium profoundly rewires metabolism, increasing glutamine consumption.
[Nature Genetics]
Najumudeen, A. K., Ceteci, F., Fey, S. K., Hamm, G., Steven, R. T., Hall, H., Nikula, C. J., Dexter, A., Murta, T., Race, A. M., Sumpton, D., Vlahov, N., Gay, D. M., Knight, J. R. P., Jackstadt, R., Leach, J. D. G., Ridgway, R. A., Johnson, E. R., Nixon, C., … Sansom, O. J. (2021). The amino acid transporter SLC7A5 is required for efficient growth of KRAS-mutant colorectal cancer. Nature Genetics, 53(1), 16–26. https://doi.org/10.1038/s41588-020-00753-3 Cite
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Colorectal Cancer Cells Enter a Diapause-Like DTP State to Survive Chemotherapy

Scientists combined cellular barcoding and mathematical modeling in patient-derived colorectal cancer models to identify and characterize drug-tolerant persisters (DTPs) in response to chemotherapy.
[Cell]
Rehman, S. K., Haynes, J., Collignon, E., Brown, K. R., Wang, Y., Nixon, A. M. L., Bruce, J. P., Wintersinger, J. A., Mer, A. S., Lo, E. B. L., Leung, C., Lima-Fernandes, E., Pedley, N. M., Soares, F., McGibbon, S., He, H. H., Pollet, A., Pugh, T. J., Haibe-Kains, B., … O’Brien, C. A. (2021). Colorectal Cancer Cells Enter a Diapause-like DTP State to Survive Chemotherapy. Cell, 184(1), 226-242.e21. https://doi.org/10.1016/j.cell.2020.11.018 Cite
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Modulation of Immune Checkpoints by Chemotherapy in Human Colorectal Liver Metastases

Scientists investigated the impact of chemotherapy on the tumor immune microenvironment. They treated human liver metastases slices with 5-fluorouracil plus either irinotecan or oxaliplatin, then performed single-cell transcriptome analyses.
[Cell Reports Medicine]
Jabbari, N., Kenerson, H. L., Lausted, C., Yan, X., Meng, C., Sullivan, K. M., Baloni, P., Bergey, D., Pillarisetty, V. G., Hood, L. E., Yeung, R. S., & Tian, Q. (2020). Modulation of Immune Checkpoints by Chemotherapy in Human Colorectal Liver Metastases. Cell Reports Medicine, 1(9). https://doi.org/10.1016/j.xcrm.2020.100160 Cite
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