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An Overview of the Tumor Microenvironment and Response to Immunotherapy in Gastrointestinal Malignancies

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Immune Strategies for Gastrointestinal Cancer

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

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Abstract

The activity of the immune system under homeostasis and disease states is governed by complex interactions of cells both through direct cell–cell contact and the secretion of soluble immunomodulatory factors. In cancer, the tumor microenvironment is increasingly being recognized as a key mediator of these interactions. The tumor microenvironment consists of a diverse milieu of malignant and stromal cells that typically constitute the tissue, as well as both tissue-resident immune cells and those that infiltrate from the circulation. It is now clear that defining factors that govern the balance between heterogeneous cell populations within the microenvironment can advance our understanding of disease progression across different malignancies. In addition, this knowledge can be leveraged to improve clinical outcomes in patients with tumors that are traditionally refractory to immunotherapy. As the development of immunotherapeutic anticancer modalities has accelerated over the past decade, it has become abundantly clear that we must investigate and understand these interactions to rationally design effective treatment regimens. In this chapter, we will outline the major players within the tumor microenvironment across prevalent gastrointestinal malignancies. Emphasis will be placed on cell types, such as fibroblasts, that play a substantial role in shaping the dynamic microenvironment of gastrointestinal cancers. We will also describe the differential response of selected gastrointestinal cancers to immunotherapy and illustrate how the microenvironment influences these responses. This chapter will provide the reader with a fundamental overview of the tumor microenvironment and immunotherapy in gastrointestinal malignancies.

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Acknowledgements

The authors would like to thank the patients and clinicians who continue to advance the field of cancer immunotherapy through their commitment to clinical research. The figures presented here were generated with BioRender.com.

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  1. Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA

    Cameron J. Herting & Gregory B. Lesinski

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Correspondence to Gregory B. Lesinski .

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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

  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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This work was supported by NIH grants R01CA208253, R01CA228406 and P30CA138292. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Conflict of Interest

Dr. Lesinski has consulted for ProDa Biotech, LLC and received compensation. Dr. Lesinski has received research funding through a sponsored research agreement between Emory University and Merck and Co., Bristol-Myers Squibb, Boerhinger-Ingelheim, and Vaccinex. Dr. Herting has no conflicts to disclose.

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Herting, C.J., Lesinski, G.B. (2021). An Overview of the Tumor Microenvironment and Response to Immunotherapy in Gastrointestinal Malignancies. In: Moehler, M., Foerster, F. (eds) Immune Strategies for Gastrointestinal Cancer. Cancer Immunotherapy, vol 2. Springer, Cham. https://doi.org/10.1007/13905_2021_1

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