The Appendix Orchestrates T-Cell Mediated Immunosurveillance in Colitis-Associated Cancer

Collard, M.; Tourneur-Marsille, Julien; Uzzan, Mathieu; Albuquerque, Miguel; Roy, Maryline; Dumay, Anne; Freund, Jean‐Noël; Hugot, Jean‐Pierre; Guedj, Nathalie; Ogier–Denis, Éric

doi:10.1016/j.jcmgh.2022.10.016

Cited by 9 publications

(5 citation statements)

References 57 publications

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“…51 The appendix also appears to play a vital role in the priming of T cells as part of innate anti-tumoral immunosurveillance via the attraction and retention of lymphocytes to the gut via α4β7 integrin, and post-appendectomy levels of CD3+ and CD8+ T-cell infiltration within the gut have been observed to be significantly decreased on immunohistochemistry staining. 52 This post-appendectomy "immune switch" further comprises of molecular changes such as a reduction in PD1 expression in CD4+ and CD8+ T cells post-appendectomy and a decreased ratio of T effector memory to T central memory cells. We further postulate that the molecular profile of CRC, namely, that of MSI-H/dMMR CRC, might also be affected by appendectomy given that the proximal pattern of presentation of CRC post-appendectomy appears to correlate with the right-sided preponderance of MSI-H/dMMR CRC, alongside recent reports that the microbiome in MSI-H/dMMR CRC is altered with increased species of Bacteroides, Prevotella, and Fusobacterium, which are species identified to be both CRC-inducing and upregulated in the post-appendectomy gut microbiome.…”

Section: Specific Pathways Of Microbiome Dysregulation Post-appendectomymentioning

confidence: 99%

“…The appendix appears to be intricately linked to immunological functions of the colon—prior appendectomy has been associated with a decreased risk of ulcerative colitis as well as a reduced risk of colectomy in patients subsequently diagnosed with ulcerative colitis, presumably as a result of immunological changes mediated by appendectomy 51 . The appendix also appears to play a vital role in the priming of T cells as part of innate anti‐tumoral immunosurveillance via the attraction and retention of lymphocytes to the gut via α4β7 integrin, and post‐appendectomy levels of CD3+ and CD8+ T‐cell infiltration within the gut have been observed to be significantly decreased on immunohistochemistry staining 52 . This post‐appendectomy “immune switch” further comprises of molecular changes such as a reduction in PD1 expression in CD4+ and CD8+ T cells post‐appendectomy and a decreased ratio of T effector memory to T central memory cells.…”

Section: Present Role Of the Appendix: Vestigial Organ Or Important R...mentioning

confidence: 99%

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Beyond a vestigial organ: effects of the appendix on gut microbiome and colorectal cancer

Yap,

Lui,

Samol

et al. 2024

J of Gastro and Hepatol

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The role of appendectomy in the pathogenesis of colorectal cancer (CRC) is a recent topic of contention. Given that appendectomy remains one of the most commonly performed operations and a first‐line management strategy of acute appendicitis, it is inherently crucial to elucidate the association between prior appendectomy and subsequent development of CRC, as there may be long‐term health repercussions. In this review, we summarize the data behind the relationship of CRC in post‐appendectomy patients, discuss the role of the microbiome in relation to appendectomy and CRC pathogenesis, and provide an appraisal of our current understanding of the function of the appendix. We seek to piece together the current landscape surrounding the microbiome and immunological changes in the colon post‐appendectomy and suggest a direction for future research involving molecular, transcriptomic, and immunologic analysis to complement our current understanding of the alterations in gut microbiome.

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Section: Specific Pathways Of Microbiome Dysregulation Post-appendectomymentioning

confidence: 99%

Section: Present Role Of the Appendix: Vestigial Organ Or Important R...mentioning

confidence: 99%

Beyond a vestigial organ: effects of the appendix on gut microbiome and colorectal cancer

Yap,

Lui,

Samol

et al. 2024

J of Gastro and Hepatol

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“…Interestingly, studies have indicated that an appendectomy may alleviate colorectal inflammation in patients with UC by reducing CD8 T cells infiltration. However, this is concomitantly associated with a heightened risk of CAC ( 55 ).…”

Section: The Mechanisms Of Cancer Associated With Ibdmentioning

confidence: 99%

Overcoming cancer risk in inflammatory bowel disease: new insights into preventive strategies and pathogenesis mechanisms including interactions of immune cells, cancer signaling pathways, and gut microbiota

Zhang,

Shi,

Lin

et al. 2024

Front. Immunol.

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Inflammatory bowel disease (IBD), characterized primarily by gastrointestinal inflammation, predominantly manifests as Crohn’s disease (CD) and ulcerative colitis (UC). It is acknowledged that Inflammation plays a significant role in cancer development and patients with IBD have an increased risk of various cancers. The progression from inflammation to carcinogenesis in IBD is a result of the interplay between immune cells, gut microbiota, and carcinogenic signaling pathways in epithelial cells. Long-term chronic inflammation can lead to the accumulation of mutations in epithelial cells and the abnormal activation of carcinogenic signaling pathways. Furthermore, Immune cells play a pivotal role in both the acute and chronic phases of IBD, contributing to the transformation from inflammation to tumorigenesis. And patients with IBD frequently exhibit dysbiosis of the intestinal microbiome. Disruption of the gut microbiota and subsequent immune dysregulation are central to the pathogenesis of both IBD and colitis associated colorectal cancer (CAC). The proactive management of inflammation combined with regular endoscopic and tumor screenings represents the most direct and effective strategy to prevent the IBD-associated cancer.

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“…Tumor-infiltrating T cells have been demonstrated to contribute to CAC immunosurveillance. Interestingly, the incidence of CAC was found to increase after an appendectomy, which may accelerate tumor development by inhibiting T-cell initiation and subsequently reducing cancer immune surveillance, as well as by dysbiosis of intestinal microbes and impairment of the intestinal barrier[ 35 , 36 ].…”

Section: Pathogenesis Of Cacmentioning

confidence: 99%

Update and latest advances in mechanisms and management of colitis-associated colorectal cancer

Dan¹,

Zhou²,

Peng³

et al. 2023

World J Gastrointest Oncol

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Colitis-associated colorectal cancer (CAC) is defined as a specific cluster of colorectal cancers that develop as a result of prolonged colitis in patients with inflammatory bowel disease (IBD). Patients with IBD, including ulcerative colitis and Crohn’s disease, are known to have an increased risk of developing CAC. Although the incidence of CAC has significantly decreased over the past few decades, individuals with CAC have increased mortality compared to individuals with sporadic colorectal cancer, and the incidence of CAC increases with duration. Chronic inflammation is generally recognized as a major contributor to the pathogenesis of CAC. CAC has been shown to progress from colitis to dysplasia and finally to carcinoma. Accumulating evidence suggests that multiple immune-mediated pathways, DNA damage pathways, and pathogens are involved in the pathogenesis of CAC. Over the past decade, there has been an increasing effort to develop clinical approaches that could help improve outcomes for CAC patients. Colonoscopic surveillance plays an important role in reducing the risk of advanced and interval cancers. It is generally recommended that CAC patients undergo endoscopic removal or colectomy. This review summarizes the current understanding of CAC, particularly its epidemiology, mechanisms, and management. It focuses on the mechanisms that contribute to the development of CAC, covering advances in genomics, immunology, and the microbiome; presents evidence for management strategies, including endoscopy and colectomy; and discusses new strategies to interfere with the process and development of CAC. These scientific findings will pave the way for the management of CAC in the near future.

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The Appendix Orchestrates T-Cell Mediated Immunosurveillance in Colitis-Associated Cancer

Cited by 9 publications

References 57 publications

Beyond a vestigial organ: effects of the appendix on gut microbiome and colorectal cancer

Beyond a vestigial organ: effects of the appendix on gut microbiome and colorectal cancer

Overcoming cancer risk in inflammatory bowel disease: new insights into preventive strategies and pathogenesis mechanisms including interactions of immune cells, cancer signaling pathways, and gut microbiota

Update and latest advances in mechanisms and management of colitis-associated colorectal cancer

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