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Cancer Immunol Res. 2017 Nov;5(11):942-949. doi: 10.1158/2326-6066.CIR-17-0375. Epub 2017 Oct 16.

A Blueprint to Advance Colorectal Cancer Immunotherapies.

Author information

1
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland.
2
Cancer Research Institute, New York, New York.
3
Division of Medical Oncology, Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina.
4
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, NCI, Bethesda, Maryland.
5
Fight Colorectal Cancer, Alexandria, Virginia.
6
The Colorado School of Public Health, Aurora, Colorado.
7
Genomics Institute of the Novartis Research Foundation, San Diego, California.
8
Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.
9
University of Wisconsin Carbone Cancer Center, University of Wisconsin, Madison, Wisconsin.
10
Ludwig Center and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland.
11
University Paris-Descartes, Cordeliers Research Centre, Paris, France.
12
The West Virginia University Mary Randolph Babb Cancer Center, Morgantown, West Virginia.
13
University of Texas, MD Anderson Cancer Center, Houston, Texas.
14
Merck & Co., Inc., Kenilworth, New Jersey.
15
Case Western Cancer Center, Cleveland, Ohio.
16
University of Colorado Cancer Center, Aurora, Colorado.
17
Memorial Sloan Kettering Cancer Center, New York, New York.
18
Bristol-Myers Squibb, Princeton, New Jersey.
19
Genentech, San Francisco, California.
20
Northwestern University, Chicago, Illinois. a-benson@northwestern.edu.

Abstract

Immunotherapy is rapidly becoming a standard of care for many cancers. However, colorectal cancer had been generally resistant to immunotherapy, despite features in common with sensitive tumors. Observations of substantial clinical activity for checkpoint blockade in colorectal cancers with defective mismatch repair (microsatellite instability-high tumors) have reignited interest in the search for immunotherapies that could be extended to the larger microsatellite stable (MSS) population. The Cancer Research Institute and Fight Colorectal Cancer convened a group of scientists, clinicians, advocates, and industry experts in colorectal cancer and immunotherapy to compile ongoing research efforts, identify gaps in translational and clinical research, and provide a blueprint to advance immunotherapy. We identified lack of a T-cell inflamed phenotype (due to inadequate T-cell infiltration, inadequate T-cell activation, or T-cell suppression) as a broad potential explanation for failure of checkpoint blockade in MSS. The specific cellular and molecular underpinnings for these various mechanisms are unclear. Whether biomarkers with prognostic value, such as the immunoscores and IFN signatures, would also predict benefit for immunotherapies in MSS colon cancer is unknown, but if so, these and other biomarkers for measuring the potential for an immune response in patients with colorectal cancer will need to be incorporated into clinical guidelines. We have proposed a framework for research to identify immunologic factors that may be modulated to improve immunotherapy for colorectal cancer patients, with the goal that the biomarkers and treatment strategies identified will become part of the routine management of colorectal cancer. Cancer Immunol Res; 5(11); 942-9. ©2017 AACR.

PMID:
29038296
DOI:
10.1158/2326-6066.CIR-17-0375
[Indexed for MEDLINE]
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