A blueprint to advance colorectal cancer immunotherapies

Dung T. Le, Vanessa M. Hubbard-Lucey, Michael A. Morse, Christopher R. Heery, Andrea Dwyer, Thomas H. Marsilje, Arthur N. Brodsky, Emily Chan, Dustin A. Deming, Luis A. Diaz, Wolf H. Fridman, Richard M. Goldberg, Stanley R. Hamilton, Franck Housseau, Elizabeth M. Jaffee, S. Peter Kang, Smitha S. Krishnamurthi, Christopher H. Lieu, Wells Messersmith, Cynthia L. Sears & 10 others Neil H. Segal, Arvin Yang, Rebecca A. Moss, Edward Cha, Jill O'Donnell-Tormey, Nancy Roach, Anjelica Q. Davis, Keavy McAbee, Sharyn Worrall, Al B Benson III

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)942-949
Number of pages8
JournalCancer Immunology Research
Volume5
Issue number11
DOIs
StatePublished - Nov 1 2017

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Immunotherapy
Colorectal Neoplasms
Microsatellite Repeats
T-Lymphocytes
Biomarkers
Neoplasms
DNA Mismatch Repair
Translational Medical Research
Immunologic Factors
Population Dynamics
Standard of Care
Research
Colonic Neoplasms
Industry
Guidelines
Phenotype

ASJC Scopus subject areas

  • Immunology
  • Cancer Research

Cite this

Le, D. T., Hubbard-Lucey, V. M., Morse, M. A., Heery, C. R., Dwyer, A., Marsilje, T. H., ... Benson III, A. B. (2017). A blueprint to advance colorectal cancer immunotherapies. Cancer Immunology Research, 5(11), 942-949. https://doi.org/10.1158/2326-6066.CIR-17-0375
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. / A blueprint to advance colorectal cancer immunotherapies. In: Cancer Immunology Research. 2017 ; Vol. 5, No. 11. pp. 942-949.
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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.",
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Le, DT, Hubbard-Lucey, VM, Morse, MA, Heery, CR, Dwyer, A, Marsilje, TH, Brodsky, AN, Chan, E, Deming, DA, Diaz, LA, Fridman, WH, Goldberg, RM, Hamilton, SR, Housseau, F, Jaffee, EM, Kang, SP, Krishnamurthi, SS, Lieu, CH, Messersmith, W, Sears, CL, Segal, NH, Yang, A, Moss, RA, Cha, E, O'Donnell-Tormey, J, Roach, N, Davis, AQ, McAbee, K, Worrall, S & Benson III, AB 2017, 'A blueprint to advance colorectal cancer immunotherapies', Cancer Immunology Research, vol. 5, no. 11, pp. 942-949. https://doi.org/10.1158/2326-6066.CIR-17-0375

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 journalArticle

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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

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Le DT, Hubbard-Lucey VM, Morse MA, Heery CR, Dwyer A, Marsilje TH et al. A blueprint to advance colorectal cancer immunotherapies. Cancer Immunology Research. 2017 Nov 1;5(11):942-949. https://doi.org/10.1158/2326-6066.CIR-17-0375