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The Microsatellite Instable Subset of Colorectal Cancer Is a Particularly Good Candidate for Checkpoint Blockade Immunotherapy
Open accessAbstract
Summary: The microsatellite instable (MSI) subset of colorectal cancer exhibits an active Th1/CTL immune microenvironment, probably due to recognition of a high number of tumor neoantigens. However, the high expression of checkpoint molecules PD-1, PD-L1, CTLA-4, LAG-3, and IDO in MSI colorectal cancer distinguishes MSI from microsatellite stable colorectal cancer and creates an immunosuppressive microenvironment that may help MSI tumors evade immune destruction by the infiltrating immune cells. Though colorectal cancer does not have a good response rate to PD-1 pathway immunotherapy, these results suggest that the MSI subset of colorectal cancer is a particularly good candidate for checkpoint immunotherapy. Cancer Discov; 5(1); 16–8. ©2015 AACR. See related article by Llosa et al., p. 43
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“It has also shown significant benefit from immune checkpoint blockade therapy, anti-PD1/PDL1 (refs. 9,10).”
From A tumor microenvironment-specific gene expression signature predicts chemotherapy resistance in colorectal cancer patients (2021) · cites this paper as [9]
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“Moreover, increasing evidence suggested that MSI tumors were responsive to immunotherapy of anti-PD1/PDL19,10.”
From A tumor microenvironment-specific gene expression signature predicts chemotherapy resistance in colorectal cancer patients (2021) · cites this paper as [9]
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Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens
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Tumor-infiltrating lymphocytes are a marker for microsatellite instability in colorectal carcinoma
Smyrk, T. C., Watson, P. A., Kaul, K. L., & Lynch, H. T. (2001) · Cancer · doi:10.1002/1097-0142(20010615)91:12 · Cited by 522
Indoleamine 2,3-dioxygenase pathways of pathogenic inflammation and immune escape in cancer
Prendergast, G. C., Smith, C., Thomas, S., Mandik‐Nayak, L., Laury‐Kleintop, L. D., Metz, R. A., & Muller, A. J. (2014) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-014-1549-4 · Cited by 491
Fusobacterium in Colonic Flora and Molecular Features of Colorectal Carcinoma
Tahara, T., Yamamoto, E., Suzuki, H., Maruyama, R., Chung, W., Garriga, J., Jelinek, J., Yamano, H.-O., Sugai, T., An, B., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-1865 · Cited by 465
Microsatellite Instability and BRAF Mutation Testing in Colorectal Cancer Prognostication
Lochhead, P. J., Kuchiba, A., Imamura, Y., Liao, X., Yamauchi, M., Nishihara, R., Qian, Z. R., Morikawa, T., Shen, J., Meyerhardt, J. A., et al. (2013) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djt173 · Cited by 442
Rudolph, B. M., Loquai, C., Gerwe, A., Bacher, N., Steinbrink, K., Grabbe, S., & Tuettenberg, A. (2014) · Experimental Dermatology · doi:10.1111/exd.12336 · Cited by 38
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Kleeff, J., Korc, M., Apte, M., La Vecchia, C., Johnson, C. D., Biankin, A. V., Neale, R. E., Tempero, M., Tuveson, D. A., Hruban, R. H., et al. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.22 · Cited by 1,982
Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy
Cannarile, M. A., Weisser, M., Jacob, W., Jegg, A.-M., Ries, C. H., & Rüttinger, D. (2017) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-017-0257-y · Cited by 1,046
DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells
Sato, H., Niimi, A., Yasuhara, T., Permata, T. B. M., Hagiwara, Y., Isono, M., Nuryadi, E., Sekine, R., Oike, T., Kakoti, S., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01883-9 · Cited by 723
Howitt, B. E., Shukla, S. A., Sholl, L. M., Ritterhouse, L. L., Watkins, J. C., Rodig, S. J., Stover, E. H., Strickland, K. C., D’Andrea, A. D., Wu, C. J., et al. (2015) · JAMA Oncology · doi:10.1001/jamaoncol.2015.2151 · Cited by 695
Fusobacterium nucleatum and T Cells in Colorectal Carcinoma
Mima, K., Sukawa, Y., Nishihara, R., Qian, Z. R., Yamauchi, M., Inamura, K., Kim, S. A., Masuda, A., Nowak, J. A., Nosho, K., et al. (2015) · JAMA Oncology · doi:10.1001/jamaoncol.2015.1377 · Cited by 669
Self-citation
Metadata
- Authors
- Xiao, Y., & Freeman, G. J.
- Affiliations
- Harvard University (US)
- Corresponding author
- Freeman, Gordon J.
- ORCID
- Freeman, Gordon J.
- Venue
- Cancer Discovery
- Published
- 2015-01-01
- Volume
- 5
- Issue
- 1
- Pages
- 16-18
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- PMC
- PMC4295637
- OpenAlex
- W2042797183
- Cited by
- 368
- References
- 11
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 17 · 2023: 26 · 2022: 54 · 2021: 44 · 2020: 36 · 2019: 46 · 2018: 35 · 2017: 40 · 2016: 37 · 2015: 14
- FWCI
- 18.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Discovery (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Public Health Service (HHSN272201100018C)
- National Cancer Institute (U54CA163125, P50CA101942)
- National Institute of Allergy and Infectious Diseases (HHSN272201100018C, P01AI056299)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Keywords
- microsatellite instability, colorectal cancer, immune checkpoint blockade, PD-1, PD-L1, CTLA-4, LAG-3, IDO, tumor immune microenvironment, neoantigens, immunosuppression, immunotherapy response
- MeSH terms
- Colonic Neoplasms, Humans, Microsatellite Instability, Tumor Microenvironment, Cell Cycle Checkpoints
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