Novel Approaches to Target the Immune System in Gastrointestinal Cancers

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Background

The increased incidence of chronic inflammatory disorders of the gastrointestinal (GI) tract has recently gained more attention as an important risk factor in the development of GI cancers. The underlying molecular mechanisms have been studied extensively, nevertheless this relationship remains poorly understood. However, in this scenario immune checkpoint mediators represent novel therapeutic targets due to their direct involvement in modulating the inflammatory reaction in the microenvironment surrounding tumors. Chronic inflammation in the GI tract is triggered and sustained by several factors including defects in the intestinal permeability, innate and adaptive immune response, the microbiome composition and environmental/nutritional factors. Chronic inflammation can trigger cellular events to promote malignant transformation of normal epithelial cells in the gastrointestinal tract to cancer.

Since the introduction of the first “biologic” agents for treatment of chronic inflammatory disorders, the management of chronic intestinal inflammation has dramatically changed as well as its repercussions on the development of GI cancers. Currently, new drugs have been approved targeting inflammatory mediators, immune cell trafficking and the inflammatory signaling pathway. Furthermore, the overall goals of any treatment have been widely adapted in the clinic (1) to improve patients’ response rate and response duration; (2) to reduce the frequency of extra-GI complications and (3) to prevent or delay the onset of cancer. Even when not directly targeted, the mucosal immune system represents the pivotal actor that is able to sustain tolerance or initiate inflammation and associate tissue degeneration. Future therapies need to consider the unique dynamic features of this complex system and be prepared to adjust interventions blocking different immunological checkpoints.

The proposed Research Topic aims to compile state-of-the-art Review, Mini-Review, and Original Research articles that summarize the current available therapeutic options and pre-clinical studies covering the following topics:

1. Targeting of the immune system (e.g. Intestinal resident Macrophages, Lymphocytes, Dendritic Cells activation and recruitment “immune cell types, signaling pathways”) to treat inflammatory disorders as well as GI cancers.
2. Role of the tumor immune microenvironment in GI tumor development and/or conversion in metaplastic versus neoplastic processes.
3. Use of immune checkpoint inhibitors in GI cancers.
4. Novel approaches able to improve the efficiency of conventional immunotherapies and delay/prevent disease recurrence and development of pre-cancerous and cancerous processes.

Keywords: immune check point, inflammation, therapy, microenvironment, immune response

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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