Understanding the immuno-biology of oesophageal adenocarcinoma: Towards improved therapeutic approaches

Lonie, James; Barbour, Andrew P.; Dolcetti, Riccardo

doi:10.1016/j.ctrv.2021.102219

Cited by 6 publications

(9 citation statements)

References 160 publications

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“…ICI is now an established therapy aimed at preventing the inhibition of the anti-tumour immune response ( 44 ). The earliest trials investigating ICIs in OAC focused on treating advanced/metastatic oesophageal or gastro-oesophageal cancers with anti-PD-1, or anti-PD-L1 monoclonal antibodies ( 6 , 51 , 52 ) and have been summarised in a previous review ( 7 ). Results varied, but overall, in the advanced/palliative setting ICI appears to improve patient survival compared to chemotherapy alone.…”

Section: Treatment Evolution In Oac and Modulation Of The Tmementioning

confidence: 99%

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Tumour microenvironment influences response to treatment in oesophageal adenocarcinoma

Belle,

Lonie,

Brosda

et al. 2023

Front. Immunol.

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The poor treatment response of oesophageal adenocarcinoma (OAC) leads to low survival rates. Its increasing incidence makes finding more effective treatment a priority. Recent treatment improvements can be attributed to the inclusion of the tumour microenvironment (TME) and immune infiltrates in treatment decisions. OAC TME is largely immunosuppressed and reflects treatment resistance as patients with inflamed TME have better outcomes. Priming the tumour with the appropriate neoadjuvant chemoradiotherapy treatment could lead to higher immune infiltrations and higher expression of immune checkpoints, such as PD-1/PDL-1, CTLA4 or emerging new targets: LAG-3, TIM-3, TIGIT or ICOS. Multiple trials support the addition of immune checkpoint inhibitors to the current standard of care. However, results vary, supporting the need for better response biomarkers based on TME composition. This review explores what is known about OAC TME, the clinical significance of the various cell populations infiltrating it and the emerging therapeutical combination with a focus on immune checkpoints inhibitors.

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Section: Treatment Evolution In Oac and Modulation Of The Tmementioning

confidence: 99%

“…Significant treatment improvement has been made in other cancer types, but ICI response in OAC is moderate. Only a minority of patients shows a complete or partial response when treated with immunotherapy ( 7 ). Treatment strategies across cancers are moving towards personalised medicine.…”

Section: Introductionmentioning

confidence: 99%

Tumour microenvironment influences response to treatment in oesophageal adenocarcinoma

Belle,

Lonie,

Brosda

et al. 2023

Front. Immunol.

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“…Tumor immune cell infiltration, inhibition of glycolysis pathway, regulation of ferroptosis, and regulation of the ceRNA network are an intense focus of research of tumor gene therapies, which are extensively applied in the research and treatment of ESCA ( Baba et al, 2020 ; Liu et al, 2021b ; Feng et al, 2021 ; Lonie et al, 2021 ; Shi et al, 2021 ; Shishido et al, 2021 ). Nevertheless, there area few studies on the thorough study of YTHDF1 in ESCA, especially the relationship between YTHDF1 and ESCA immune cell infiltration, glycolysis, ferroptosis, and the ceRNA network.…”

Section: Introductionmentioning

confidence: 99%

“…Although radical resection, radiotherapy, and chemotherapy for ESCA have made significant progress, the 5-year survival rate of ESCA patients is still very low ( Kelly, 2019 ; Yang et al, 2020a ; Thrift, 2021 ). The occurrence, development, and recurrence of ESCA involve a variety of important signal transduction pathways and biological functions in the human body ( Yang et al, 2020b ; Liu et al, 2021a ; Lonie et al, 2021 ; Thrift, 2021 ). Therefore, finding biomarkers involving multiple biological functions and exploring the pathogenesis of ESCA can provide a better reference for tumor diagnosis and treatment.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis of YTHDF1 Immune Infiltrates and ceRNA in Human Esophageal Carcinoma

et al. 2022

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Background: YTHDF1 is highly expressed in multiple tumors and affects tumor progression. However, there are only a few comprehensive studies on the analysis of YTHDF1 in esophageal cancer.Methods: We analyzed YTHDF1 expression in pan-cancer by comparing both the GEPIA and TCGA cohorts, and further verified the differences in YTHDF1 expression between the ESCA and normal groups by the GEO ESCA cohort and in vitro experiments. The correlation of YTHDF1 expression and the clinical characteristics of ESCA patients was analyzed using the TCGA ESCA clinical data. The GO and KEGG enrichment analyses of the YTHDF1 coexpressed genes were completed by bioinformatics analysis, and the GGI and PPI were constructed for the YTHDF1, respectively. The relationship between YTHDF1 expression and the infiltration of ESCA immune cells was analyzed by using the TIMER database and the TCGA ESCA cohort. The relationships between YTHDF1 expression levels and glycolysis and ferroptosis-related genes were analyzed using the TCGA and GEPIA ESCA cohorts. Finally, the ceRNA network that may be involved in YTHDF1 in ESCA was predicted and constructed through a variety of databases.Results: YTHDF1 was overexpressed in various cancers, and in vitro experiments confirmed that YTHDF1 expression was higher in ESCA samples than in normal samples. The expression of YTHDF1 has some accuracy in predicting the tumor outcome. Expression of YTHDF1 was significantly associated with multiple clinical features in ESCA patients. GO and KEGG enrichment analyses indicated that YTHDF1 coexpressed genes involved multiple biological functions. There is a potential association between YTHDF1 expression and multiple immune cell infiltration, glycolysis, and ferroptosis-related genes in ESCA. YTHDF1 may be involved in multiple ceRNA regulatory networks in ESCA, including PAXIP1-AS1/hsa-miR-376c-3p/YTHDF1 axis, THUMPD3-AS1/hsa-miR-655-3p/YTHDF1 axis, and SNHG20/hsa-miR-655-3p/YTHDF1 axis, respectively.Conclusion: YTHDF1 can serve as a biomarker of ESCA, related to the immune cell infiltration of ESCA, regulation of glycolysis and ferroptosis, and the ceRNA regulatory network.

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“…In EC, the tumor–immune microenvironment is largely immunosuppressive and pro-tumorigenic, characterised by an exhausted adaptive immune response in addition to a predominant infiltration by neutrophil-like, myeloid-derived suppressor cells (MDSC). 2 Research into the effects of chemotherapy and/or radiation on the tumor–immune microenvironment have largely concluded that these treatments have immunostimulatory and abscopal effects, which lead to an immunogenic tumor cell death response mediated by T-cell priming and antigen presentation. 3 However, emerging evidence suggests that subjecting solid tumors with a preexisting, immunosuppressive microenvironment to neoadjuvant treatment may, in fact, further enhance immunosuppression through a number of mechanisms involving the chronic inflammatory response and its mediators enhancing the effects of MDSCs and the polarization of other immune cells to a pro-tumorigenic state.…”

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confidence: 99%

Tumor-Infiltrating Neutrophils after Neoadjuvant Therapy are Associated with Poor Prognosis in Esophageal Cancer

et al. 2022

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Background In esophageal cancer (EC), there is a paucity of knowledge regarding the interplay between the tumor immune microenvironment and response to neoadjuvant treatment and, therefore, which factors may influence outcomes. Thus, our goal was to investigate the changes in the immune microenvironment with neoadjuvant treatment in EC by assessing the expression of immune related genes and their association with prognosis. Methods We examined the transcriptome of paired pre- and post-neoadjuvant treated EC specimens. Based on these findings, we validated the presence of tumor-infiltrating neutrophils using CD15+ immunohistochemistry in a discovery cohort of patients with residual pathologic disease. We developed a nomogram as a predictor of progression-free survival (PFS) incorporating the variables CD15+ cell count, tumor regression grade, and tumor grade. Results After neoadjuvant treatment, there was an increase in genes related to myeloid cell differentiation and a poor prognosis associated with high neutrophil (CD15+) counts. Our nomogram incorporating CD15+ cell count was predictive of PFS with a C-index of 0.80 (95% confidence interval [CI] 0.68–0.9) and a concordance probability estimate (CPE) of 0.77 (95% CI 0.69–0.86), which indicates high prognostic ability. The C-index and CPE of the validation cohort were 0.81 (95% CI 0.69–0.91) and 0.78 (95% CI 0.7–0.86), respectively. Conclusions Our nomogram incorporating CD15+ cell count can potentially be used to identify patients at high risk of recurrent disease and thus stratify patients who will benefit most from adjuvant treatment.

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Understanding the immuno-biology of oesophageal adenocarcinoma: Towards improved therapeutic approaches

Cited by 6 publications

References 160 publications

Tumour microenvironment influences response to treatment in oesophageal adenocarcinoma

Tumour microenvironment influences response to treatment in oesophageal adenocarcinoma

Comprehensive Analysis of YTHDF1 Immune Infiltrates and ceRNA in Human Esophageal Carcinoma

Tumor-Infiltrating Neutrophils after Neoadjuvant Therapy are Associated with Poor Prognosis in Esophageal Cancer

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