Immune determinants of Barrett’s progression to esophageal adenocarcinoma

Lagisetty, Kiran H.; McEwen, Dyke P.; Nancarrow, Derek J.; Schiebel, Johnathon G; Ferrer-Torres, Daysha; Ray, Dipankar; Frankel, Timothy L.; Lin, Jules; Chang, Andrew C.; Kresty, Laura A.; Beer, David G.

doi:10.1172/jci.insight.143888

Cited by 32 publications

(48 citation statements)

References 70 publications

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“…Other than this, the increase of eosinophils is also found in some ESCC patients (107), positively correlating with low incidence of LN metastasis in patients with early ESCC and predicting favorable OS in ESCC patients treated with concurrent chemoradiotherapy (108,109). Conversely, eosinophils appear to be significantly reduced across all stages of dysplasia and EAC progression, indicating the loss of immune surveillance by eosinophils may contribute to BE progression toward dysplasia and cancer (110). Indeed, eosinophils play controversial roles in modulating tumor initiation and progression, for that they are both the source of antitumorigenic factors including TNF-a, granzyme, cationic proteins, and IL-18, and protumorigenic molecules such as pro-angiogenic factors, depending on the different immune milieu (35).…”

Section: Mcs and Eosinophilsmentioning

confidence: 99%

Innate Immune Cells in the Esophageal Tumor Microenvironment

Cui

Mei

et al. 2021

Front. Immunol.

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Esophageal cancer (EC) is one of the most common mucosa-associated tumors, and is characterized by aggressiveness, poor prognosis, and unfavorable patient survival rates. As an organ directly exposed to the risk of foodborne infection, the esophageal mucosa harbors distinct populations of innate immune cells, which play vital roles in both maintenance of esophageal homeostasis and immune defense and surveillance during mucosal anti-infection and anti-tumor responses. In this review, we highlight recent progress in research into innate immune cells in the microenvironment of EC, including lymphatic lineages, such as natural killer and γδT cells, and myeloid lineages, including macrophages, dendritic cells, neutrophils, myeloid-derived suppressor cells, mast cells and eosinophils. Further, putative innate immune cellular and molecular mechanisms involved in tumor occurrence and progression are discussed, to highlight potential directions for the development of new biomarkers and effective intervention targets, which can hopefully be applied in long-term multilevel clinical EC treatment. Fully understanding the innate immunological mechanisms involved in esophageal mucosa carcinogenesis is of great significance for clinical immunotherapy and prognosis prediction for patients with EC.

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Section: Mcs and Eosinophilsmentioning

confidence: 99%

Innate Immune Cells in the Esophageal Tumor Microenvironment

Cui

Mei

et al. 2021

Front. Immunol.

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“…RNA‐Seq and the genomic cellular analysis tool xCell revealed a linear increase in Th1, Th2, Treg, and pro–B cell populations in EAC compared with precancerous lesions (dysplastic BE and NDBE) as well as a linear increase in M1 and M2 macrophages between HGD and EAC. 245 Although multiplex IHC showed that immune cell populations tended to increase in a stepwise fashion from BE to LGD to HGD, followed by a decline in all evaluated immune cell populations in EAC tissues that coincided with increased PD‐L1 expression. 245 PD‐L1 has been shown to cause T cell apoptosis and suppress antitumor immunity.…”

Section: Microenvironment Markers In Progression To Barrett's Adenocarcinomamentioning

confidence: 93%

“… 245 Although multiplex IHC showed that immune cell populations tended to increase in a stepwise fashion from BE to LGD to HGD, followed by a decline in all evaluated immune cell populations in EAC tissues that coincided with increased PD‐L1 expression. 245 PD‐L1 has been shown to cause T cell apoptosis and suppress antitumor immunity. 246 , 247 PD‐L1 expression in subset of EAC patients means that these individuals may benefit from immunomodulatory therapy, such as anti–PD‐1, anti–PD‐L1 or anti‐CTLA4 therapy.…”

Section: Microenvironment Markers In Progression To Barrett's Adenocarcinomamentioning

confidence: 93%

Barrett's esophagus: The pathomorphological and molecular genetic keystones of neoplastic progression

et al. 2021

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Barrett's esophagus is a widespread chronically progressing disease of heterogeneous nature. A life threatening complication of this condition is neoplastic transformation, which is often overlooked due to lack of standardized approaches in diagnosis, preventative measures and treatment. In this essay, we aim to stratify existing data to show specific associations between neoplastic transformation and the underlying processes which predate cancerous transition. We discuss pathomorphological, genetic, epigenetic, molecular and immunohistochemical methods related to neoplasia detection on the basis of Barrett's esophagus. Our review sheds light on pathways of such neoplastic progression in the distal esophagus, providing valuable insight into progression assessment, preventative targets and treatment modalities. Our results suggest that molecular, genetic and epigenetic alterations in the esophagus arise earlier than cancerous transformation, meaning the discussed targets can help form preventative strategies in at-risk patient groups.

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“…Changes in the immune profile during BE-to-EAC progression have been identified by RNA-sequencing of 65 BE/dysplasia/EAC samples [ 51 ]. A subset of chemokines and cytokines, in particular, IL6 and CXCL8, increased during BE progression to EAC.…”

Section: Transcriptomics Of Eacmentioning

confidence: 99%

Genomic and Transcriptomic Characteristics of Esophageal Adenocarcinoma

Hoppe

Jonas

Wenzel

et al. 2021

Cancers

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Esophageal adenocarcinoma (EAC) is a deadly disease with limited options for targeted therapy. With the help of next-generation sequencing studies over the last decade, we gained an understanding of the genomic architecture of EAC. The tumor suppressor gene TP53 is mutated in 70 to 80% of tumors followed by genomic alterations in CDKN2A, KRAS, ERBB2, ARID1A, SMAD4 and a long tail of less frequently mutated genes. EAC is characterized by a high burden of point mutations and genomic rearrangements, resulting in amplifications and deletions of genomic regions. The genomic complexity is likely hampering the efficacy of targeted therapies. Barrett’s esophagus (BE), a metaplastic response of the esophagus to gastro-esophageal reflux disease, is the main risk factor for the development of EAC. Almost all EACs are derived from BE. The sequence from BE to EAC provides an opportunity to study the genomic evolution towards EAC. While the overlap of point mutations between BE and EAC within the same patient is, at times, surprisingly low, there is a correlation between the complexity of the genomic copy number profile and the development of EAC. Transcriptomic analyses separated EAC into a basal and a classical subtype, with the basal subtype showing a higher level of resistance to chemotherapy. In this review, we provide an overview of the current knowledge of the genomic and transcriptomic characteristics of EAC and their relevance for the development of the disease and patient care.

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Immune determinants of Barrett’s progression to esophageal adenocarcinoma

Cited by 32 publications

References 70 publications

Innate Immune Cells in the Esophageal Tumor Microenvironment

Innate Immune Cells in the Esophageal Tumor Microenvironment

Barrett's esophagus: The pathomorphological and molecular genetic keystones of neoplastic progression

Genomic and Transcriptomic Characteristics of Esophageal Adenocarcinoma

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