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. SearsNeil 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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

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 2017

Funding

M.A. Morse reports receiving commercial research support from Bristol-Myers Squibb and Merck. C.R. Heery is the chief medical officer at and has ownership interest in Bavarian Nordic. D.A. Deming is a consultant/ advisory board member for Bristol-Myers Squibb. L.A. Diaz is on the board of directors at PGDx, has ownership interest in PapGene and PGDx, and is a consultant/advisory board member for Merck and PGDx. W.H. Fridman is a consultant/advisory board member for Adaptimmune and Novartis. E.M. Jaffee reports receiving commercial research support from Amgen and Bristol-Myers Squibb. C.L. Sears reports receiving a commercial research grant from and is a consultant/advisory board member for Bristol-Myers Squibb. N.H. Segal reports receiving commercial research support from Bristol-Myers Squibb, MedImmune/AstraZeneca, Merck, and Roche/ Genentech and is a consultant/advisory board member for Bristol-Myers Squibb, MedImmune/AstraZeneca, Merck, Pfizer, and Roche/Genentech. R.A. Moss is the medical director at and has ownership interest (including patents) in Bristol-Myers Squibb. A.B. Benson reports receiving commercial research grants from Genentech and Merck and is a consultant/advisory board member for Bristol-Myers Squibb, Genentech, and Merck. No potential conflicts of interest were disclosed by the other authors.

ASJC Scopus subject areas

  • Cancer Research
  • Immunology

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