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Biomarkers for Immunotherapy in Gastrointestinal Cancers

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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 represents one of the most promising emerging therapies for the treatment of gastrointestinal (GI) cancers. As for targeted therapies, the results of the first trials have underlined the need for biomarkers to select patients who benefit from these molecules. After the first studies conducted in colorectal cancer, mismatch repair (MMR) deficiency, resulting in microsatellite instability (MSI), has been identified to predict response and survival to immunotherapy regardless of tumor origin. More recently, an elevated tumor mutational burden (TMB) was also validated as a tumor-origin independent predictive biomarker for response to pembrolizumab. Following the emerging concept of molecular diagnosis, the Food and Drug Administration (FDA) approved MSI/MMR deficiency and high-TMB as criteria for the indication of immunotherapy regardless of tumor origin. As in non-GI tumor locations, such as broncho-pulmonary cancer, PD-L1 overexpression in tumor cells and/or in immune cells of the tumor microenvironment has been identified and validated by the FDA as a biomarker for response to immunotherapy in gastric and esophageal cancers. However, optimal assessment method and definition of PD-L1 overexpression are still under investigation. Other immune-related biomarkers such as tumor-infiltrating lymphocyte assessment, inflamed-gene expression, or circulating neutrophil-to-lymphocyte ratio might correlate to response and/or survival in several tumor locations, but need to be further investigated. Lastly, several tumor location specific parameters appear to be promising biomarkers in selected indications, such as POLE mutations in colorectal cancer, EBV status in gastric cancer, and HPV status in anal cancer.

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Authors and Affiliations

  1. Gastroenterology and Digestive Oncology Department, Georges Pompidou European Hospital, APHP, Université de Paris, Paris, France

    Juliette Palle, Julien Taïeb & Aziz Zaanan

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  1. Juliette Palle
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  2. Julien Taïeb
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  3. Aziz Zaanan
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Correspondence to Aziz Zaanan .

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Editors and Affiliations

  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

  2. First Department of Medicine, University Cancer Center Mainz, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany

    Friedrich Foerster

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JP has participated in consulting or advisory boards for Amgen and Servier.

JT received honoraria for speaker or advisory role from: Amgen, Baxter, BMS, MSD, Merck, Pierre Fabre, Roche, Sanofi, Servier.

AZ has participated in consulting and/or advisory boards for Amgen, Lilly, Merck, Roche, Sanofi, Servier, Baxter, MSD, Pierre Fabre, Havas Life, Alira Health, Zymeworks.

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Palle, J., Taïeb, J., Zaanan, A. (2021). Biomarkers for Immunotherapy in Gastrointestinal Cancers. In: Moehler, M., Foerster, F. (eds) Immune Strategies for Gastrointestinal Cancer. Cancer Immunotherapy, vol 2. Springer, Cham. https://doi.org/10.1007/13905_2021_10

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  • DOI: https://doi.org/10.1007/13905_2021_10

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