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Immunotherapy in the Treatment of Advanced Colorectal Cancer

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Immune Strategies for Gastrointestinal Cancer

Part of the book series: Cancer Immunotherapy ((CAIMUN,volume 2))

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Abstract

Immunotherapy has rapidly evolved in the treatment of select malignancies. In colorectal cancer, response to treatment has varied based on the presence of mismatch repair deficiency (dMMR) and microsatellite instability (MSI-H). Patients with dMMR/MSI-H metastatic colorectal cancer (mCRC) have a favorable tumor microenvironment (TME) resulting in activation of the immune system and targeting of the malignancy by T and NK cells leading to a good response to immune checkpoint inhibitors (ICIs). Pembrolizumab and nivolumab are ICIs that target programmed cell death protein 1. Nivolumab is FDA approved for the treatment of dMMR/MSI-H mCRC after initial chemotherapy regimens have failed, while pembrolizumab is now approved for first-line treatment. However, at least 96% of metastatic colorectal cancers are pMMR/MSS and do not exhibit responses to treatment with ICIs. Studies are exploring therapeutic combinations with targets such as BRAF, VEGF, and others that may activate T and NK cells, reduce inhibitory signals, and increase robustness of the immune response.

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  1. Puneet Raman and Gehan Botrus contributed equally with all other contributors.

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  1. Mayo Clinic College of Medicine and Science, Phoenix, AZ, USA

    Puneet Raman, Gehan Botrus & Tanios Bekaii-Saab

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  1. First Department of Medicine, Research Center for Immunotherapy (FZI), University Cancer Center Mainz, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany

    Markus Moehler

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Conflict of Interest: Puneet Raman, M.D., declares no conflicts of interest that might be relevant to the contents of this manuscript.

Gehan Botrus, M.D., Ph.D., declares no conflicts of interest that might be relevant to the contents of this manuscript.

Tanios S. Bekaii-Saab, M.D., declares: Research Funding (to institution): Boston Biomedical, Bayer, Amgen, Merck, Celgene, Lilly, Ipsen, Clovis, Seattle Genetics, Array Biopharma, Genentech, Abgenomics, Incyte, and eBMS. Consulting (to institution): Ipsen, Array Biopharma, Seattle Genetics, Bayer, Genentech, Incyte, and Merck. Consulting (to self): Boehringer Ingelheim, TreosBio, and Sobi. IDMC/DSMB (to self): AstraZeneca, Exelixis, Lilly, PanCan, and 1Globe. Scientific Advisory Board: Imugene, Immuneering, and Sun Biopharma. Inventions/Patents: WO/2018/183488 and WO/2019/055687.

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Raman, P., Botrus, G., Bekaii-Saab, T. (2022). Immunotherapy in the Treatment of Advanced Colorectal Cancer. In: Moehler, M., Foerster, F. (eds) Immune Strategies for Gastrointestinal Cancer. Cancer Immunotherapy, vol 2. Springer, Cham. https://doi.org/10.1007/13905_2021_12

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