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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 942-949 |
| Number of pages | 8 |
| Journal | Cancer Immunology Research |
| Volume | 5 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 1 2017 |
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ASJC Scopus subject areas
- Immunology
- Cancer Research
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A blueprint to advance colorectal cancer immunotherapies. / Le, Dung T.; Hubbard-Lucey, Vanessa M.; Morse, Michael A.; Heery, Christopher R.; Dwyer, Andrea; Marsilje, Thomas H.; Brodsky, Arthur N.; Chan, Emily; Deming, Dustin A.; Diaz, Luis A.; Fridman, Wolf H.; Goldberg, Richard M.; Hamilton, Stanley R.; Housseau, Franck; Jaffee, Elizabeth M.; Kang, S. Peter; Krishnamurthi, Smitha S.; Lieu, Christopher H.; Messersmith, Wells; Sears, Cynthia L.; Segal, Neil H.; Yang, Arvin; Moss, Rebecca A.; Cha, Edward; O'Donnell-Tormey, Jill; Roach, Nancy; Davis, Anjelica Q.; McAbee, Keavy; Worrall, Sharyn; Benson III, Al B.
In: Cancer Immunology Research, Vol. 5, No. 11, 01.11.2017, p. 942-949.Research output: Contribution to journal › Article
TY - JOUR
T1 - A blueprint to advance colorectal cancer immunotherapies
AU - Le, Dung T.
AU - Hubbard-Lucey, Vanessa M.
AU - Morse, Michael A.
AU - Heery, Christopher R.
AU - Dwyer, Andrea
AU - Marsilje, Thomas H.
AU - Brodsky, Arthur N.
AU - Chan, Emily
AU - Deming, Dustin A.
AU - Diaz, Luis A.
AU - Fridman, Wolf H.
AU - Goldberg, Richard M.
AU - Hamilton, Stanley R.
AU - Housseau, Franck
AU - Jaffee, Elizabeth M.
AU - Kang, S. Peter
AU - Krishnamurthi, Smitha S.
AU - Lieu, Christopher H.
AU - Messersmith, Wells
AU - Sears, Cynthia L.
AU - Segal, Neil H.
AU - Yang, Arvin
AU - Moss, Rebecca A.
AU - Cha, Edward
AU - O'Donnell-Tormey, Jill
AU - Roach, Nancy
AU - Davis, Anjelica Q.
AU - McAbee, Keavy
AU - Worrall, Sharyn
AU - Benson III, Al B
PY - 2017/11/1
Y1 - 2017/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85033361545&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85033361545&partnerID=8YFLogxK
U2 - 10.1158/2326-6066.CIR-17-0375
DO - 10.1158/2326-6066.CIR-17-0375
M3 - Article
VL - 5
SP - 942
EP - 949
JO - Cancer immunology research
JF - Cancer immunology research
SN - 2326-6066
IS - 11
ER -