The Microsatellite Instable Subset of Colorectal Cancer Is a Particularly Good Candidate for Checkpoint Blockade Immunotherapy

Xiao, Yanping; Freeman, Gordon J.

doi:10.1158/2159-8290.cd-14-1397

Cited by 374Cancer Immunotherapy and BiomarkersGenetic factors in colorectal cancerColorectal Cancer Treatments and Studies

The Microsatellite Instable Subset of Colorectal Cancer Is a Particularly Good Candidate for Checkpoint Blockade Immunotherapy

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Xiao, Yanping, Freeman, Gordon J.·2015·Cancer Discovery

DOI 10.1158/2159-8290.cd-14-1397PMC PMC4295637

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Abstract

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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MSI tumors have significant benefit from immune checkpoint blockade therapy, anti-PD1/PDL1.
“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]
The Abstract identifies MSI colorectal cancer as a promising candidate for checkpoint immunotherapy, but it does not report significant clinical benefit in MSI tumors. It says colorectal cancer had responded poorly to PD-1/PD-L1 blockade in earlier trials and that trials specifically testing PD-1 blockade in MSI patients had only been initiated. The reported durable efficacy was in melanoma, renal cancer, and non-small cell lung cancer. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Increasing evidence suggested that MSI tumors were responsive to immunotherapy of anti-PD1/PDL1.
“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]
The Abstract says MSI colorectal tumors are particularly good candidates for checkpoint immunotherapy, based on their immune microenvironment. It does not report that MSI tumors responded to anti-PD-1 or anti-PD-L1 treatment; it says PD-1 blockade trials in MSI patients had been initiated and that colorectal cancer overall had responded poorly in earlier trials. (LLM, conf=0.86)
Experimental — accuracy not yet measured

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[1]Smyrk TC Watson P Kaul K Lynch HT Tumor-infiltrating lymphocytes are a marker for microsatellite instability in colorectal carcinoma Cancer 2001 91 2417 22 11413533

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IN THE SPOTLIGHT The Microsatellite Instable Subset of Colorectal Cancer Is a Particularly Good Candidate for Checkpoint Blockade Immunotherapy
Xiao, Y., & Freeman, G. J. (2016)
Self-citation
Overview of Microsatellite Instability and Immune Checkpoint Inhibitors in Colorectal Cancer
Kim, D. W., Lee, J.-H., Kim, K., & Imanirad, I. (2018) · Current Colorectal Cancer Reports · doi:10.1007/s11888-018-0413-x
The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints
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Abstract A141: The vigorous immune microenvironment of microsatellite instable colon cancer isbalanced by multiple counter-inhibitory checkpoints
Llosa, N. J., Housseau, F., Wick, E. C., Hechenbleikner, L., Cruise, M. W., Anders, R. A., Sears, C. L., Pardoll, D. M., Fan, H., Siegel, N. M., et al. (2016) · Cancer Immunology Research · doi:10.1158/2326-6074.cricimteatiaacr15-a141
Abstract 451: The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints
Llosa, N. J., Cruise, M. W., Tam, A. J., Wick, E., Hechenbleikner, E. M., Taube, J. M., Blosser, L., Fan, H., Wang, H., Zhang, M., et al. (2015) · Cancer Research · doi:10.1158/1538-7445.am2015-451 · Cited by 6 · see citing works

Authors: Xiao, Y., & Freeman, G. J.
Affiliations: Harvard University (US)
Corresponding author: Freeman, Gordon J.
ORCID: Freeman, Gordon J.
Venue: Cancer Discovery
Publisher: American Association for Cancer Research (AACR)
Published: 2015-01-01
Volume: 5
Issue: 1
Pages: 16-18
ISSN: 2159-8274 (ISSN-L)
2159-8290
DOI: 10.1158/2159-8290.cd-14-1397
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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The Microsatellite Instable Subset of Colorectal Cancer Is a Particularly Good Candidate for Checkpoint Blockade Immunotherapy

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