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Innate Immune Pattern Recognition and the Development of Intestinal Cancer

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Microbiome and Cancer

Part of the book series: Current Cancer Research ((CUCR))

Abstract

Inflammation and cancer have been connected since Virchow’s pathologic examination of tumors revealed widespread immune cell infiltration. It is only recently, however, that a mechanistic understanding of this association has emerged. Pattern recognition receptors (PRRs), host receptors that transmit signals after binding moieties found in microbes or released by the host in response to injury, are one such molecular link. Recent work has established the importance of microbe-host signaling, mediated by PRRs, in a range of inflammatory responses, including the development and inhibition of cancer. Here, we review pattern recognition receptors and the implications of their activation on cancer. We focus on cancers in the gastrointestinal tract, the site of the greatest magnitude and diversity of the microbiota in humans. Signaling through PRRs impacts every stage of intestinal cancer, from the early phases of initiation to metastatic spread, and diverse cell types found in the tumor microenvironment, from neoplastic cells themselves to immune and stromal cells. We highlight recent discoveries that support a model in which tumors progress by exploiting PRR signaling. We argue that the tumor microenvironment exposes diverse signals from an altered microbiota and the host itself that converge on pattern recognition receptors, thereby perpetuating tumor growth. Analogous to pathogens, tumors orchestrate their own survival, which we propose occurs by both inducing and benefitting from alterations in host-associated microbial colonization.

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Authors and Affiliations

  1. Division of Infectious Diseases, Department of Medicine, Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA

    Steven J. Siegel & Seth Rakoff-Nahoum

  2. Division of Gastroenterology, Department of Medicine, Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA

    Seth Rakoff-Nahoum

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  1. Steven J. Siegel
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  2. Seth Rakoff-Nahoum
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Correspondence to Seth Rakoff-Nahoum .

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  1. Department of Otorhinolaryngology – Head and Neck Surgery Abramson Comprehensive Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Erle S. Robertson

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Siegel, S.J., Rakoff-Nahoum, S. (2019). Innate Immune Pattern Recognition and the Development of Intestinal Cancer. In: Robertson, E. (eds) Microbiome and Cancer. Current Cancer Research. Humana Press, Cham. https://doi.org/10.1007/978-3-030-04155-7_14

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