Abstract 2826: Understanding associations among local microbiome, immune response, and efficacy of immunotherapy in esophageal cancer

Abstract Background In cancer cells, DNA methylation may be altered in two principle ways; global DNA hypomethylation and site-specific CpG island promoter hypermethylation. Since Long interspersed element-1 (LINE-1 or L1; a repetitive DNA retrotransposon) constitutes a substantial portion (approximately 17%) of the human genome, the extent of LINE-1 methylation is regarded as a surrogate marker of global DNA methylation. In previous studies, we demonstrated that LINE-1 hypomethylation was strongly associated with a poor prognosis in esophageal cancer, supporting its potential role as a prognostic marker (Ann Surg 2012). We also found that LINE-1-hypomethylated tumors showed highly frequent genomic gains at various loci containing candidate oncogenes such as CDK6 (Clin Cancer Res 2014). Given that immunotherapy, as represented by PD-1/PD-L1-targeting antibodies, has increasingly gained attention as a novel treatment strategy for esophageal cancer, better understanding of local immune response status in esophageal cancer is important. The aim of this study is to evaluate the relationship between LINE-1 methylation level and local immune response in esophageal cancer. Methods Using a non-biased database of 305 curatively resected esophageal cancers, we evaluated PD-L1 expression and TIL status (CD8 expression) by immunohistochemical analysis (Ann Surg 2017). Results TIL positivity was significantly correlated with longer overall survival (log-rank P < 0.0001). TIL-negative cases demonstrated significantly lower LINE-1 methylation level compared with TIL-positive cases (P = 0.012). This finding certainly supports that LINE-1 methylation level may influence the local immune response status. Conclusion PD-L1 expression was not related with LINE-1 methylation level. Further investigations in this field would provide deeper insights into esophageal tumor immunology and assist the development of new therapeutic strategies against esophageal cancer. Disclosure All authors have declared no conflicts of interest.

Download Full-text

A Dendritic Cell Vaccine Combined With Radiotherapy Activates the Specific Immune Response in Patients With Esophageal Cancer

Journal of Immunotherapy ◽

10.1097/cji.0000000000000155 ◽

2017 ◽

Vol 40 (2) ◽

pp. 71-76 ◽

Cited By ~ 11

Author(s):

Chengshi Wang ◽

Juan Pu ◽

Hanxu Yu ◽

Yanyan Liu ◽

Honghuan Yan ◽

...

Keyword(s):

Immune Response ◽

Esophageal Cancer ◽

Dendritic Cell ◽

Dendritic Cell Vaccine ◽

Specific Immune Response ◽

Cell Vaccine

Download Full-text

The Intensity of Radiotherapy-Elicited Immune Response Is Associated with Esophageal Cancer Clearance

Journal of Immunology Research ◽

10.1155/2014/794249 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 6

Author(s):

Jin-lu Ma ◽

Long Jin ◽

Yao-Dong Li ◽

Chen-chen He ◽

Xi-jing Guo ◽

...

Keyword(s):

Immune Response ◽

Dna Damage ◽

Esophageal Cancer ◽

Immune Cells ◽

Interleukin 2 ◽

Therapeutic Interventions ◽

Hematologic Toxicity ◽

Serum Concentrations ◽

Local Response ◽

Therapeutic Modalities

Radiation therapy is one of the standard therapeutic modalities for esophageal cancer, achieving its main antitumor efficacy through DNA damage. However, accumulating evidence shows that radiotherapy can substantially alter the tumor microenvironment, particularly with respect to its effects on immune cells. We hypothesized that the immune response elicited by radiotherapy may be as important as the radiation itself for successful treatment. More specifically, immunomodulatory cytokines may enhance the effectiveness of radiotherapy. To investigate this hypothesis, we measured changes in the serum interferon-gamma (IFN-γ) and interleukin-2 (IL-2) concentrations during radiotherapy and compared these modifications with outcomes. We found that serum concentrations of IL-2 and IFN-γwere positively associated with local response to radiotherapy in esophageal cancer. More generally, the intensity of the radiotherapy-elicited immune response was positively associated with local response to radiotherapy in esophageal cancer. Changes in serum IL-2 and IFN-γconcentrations were further associated with increased risks of acute hematologic toxicity and acute organ toxicity of the esophagus, lung, and skin. These results suggest that deciphering the mechanisms of radiotherapy-elicited immune response may help in the development of therapeutic interventions that would enhance the efficacy of radiotherapy and convert some ineffective responses to effective responses.

Download Full-text

Analysis of peripheral and local anti-tumor immune response in esophageal cancer patients after NY-ESO-1 protein vaccination

International Journal of Cancer ◽

10.1002/ijc.23810 ◽

2008 ◽

Vol 123 (10) ◽

pp. 2362-2369 ◽

Cited By ~ 36

Author(s):

Hisashi Wada ◽

Eiichi Sato ◽

Akiko Uenaka ◽

Midori Isobe ◽

Ryohei Kawabata ◽

...

Keyword(s):

Immune Response ◽

Esophageal Cancer ◽

Cancer Patients

Download Full-text

Safety and antibody immune response of CHP-NY-ESO-1 vaccine combined with poly-ICLC in advanced or recurrent esophageal cancer patients

Cancer Immunology Immunotherapy ◽

10.1007/s00262-021-02892-w ◽

2021 ◽

Author(s):

Takeshi Ishikawa ◽

Shinichi Kageyama ◽

Yoshihiro Miyahara ◽

Tetsuya Okayama ◽

Satoshi Kokura ◽

...

Keyword(s):

Immune Response ◽

Esophageal Cancer ◽

Cancer Patients

Download Full-text

Tumor Long-interspersed Nucleotide Element-1 Methylation Level and Immune Response to Esophageal Cancer

Annals of Surgery ◽

10.1097/sla.0000000000003264 ◽

2019 ◽

Vol 272 (6) ◽

pp. 1025-1034 ◽

Cited By ~ 2

Author(s):

Keisuke Kosumi ◽

Yoshifumi Baba ◽

Kazuo Okadome ◽

Taisuke Yagi ◽

Yuki Kiyozumi ◽

...

Keyword(s):

Immune Response ◽

Esophageal Cancer ◽

Methylation Level

Download Full-text

Metformin Downregulates PD-L1 Expression in Esophageal Squamous Cell Catrcinoma by Inhibiting IL-6 Signaling Pathway

Frontiers in Oncology ◽

10.3389/fonc.2021.762523 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yao Lu ◽

Dao Xin ◽

Lulu Guan ◽

Mengli Xu ◽

Yalan Yang ◽

...

Keyword(s):

Immune Response ◽

Esophageal Cancer ◽

T Cell ◽

Signaling Pathway ◽

Squamous Cell ◽

Antitumor Immune Response ◽

Cancer Data ◽

Stat3 Signaling ◽

Coculture System ◽

Stat3 Signaling Pathway

PurposeTo characterize the mechanism by which metformin inhibits PD-L1 expression in esophageal squamous cell carcinoma (ESCC) and to evaluate the effect of metformin on the antitumor immune response.MethodsThe Cancer Genome Atlas (TCGA) database was used to analyze the correlations between IL-6 and prognosis and between IL-6 and PD-L1 gene expression in esophageal cancer. Reverse transcription-quantitative polymerase chain reaction (RT-PCR), Western blotting and immunofluorescence were used to study the mechanism by which metformin affects PD-L1 expression. Additionally, T cell function was assessed in a coculture system containing ESCC cells and peripheral blood mononuclear cells (PBMCs) treated with metformin or IL-6. In an in vivo assay, we used a model established with NPIdKO™ mice, which have a reconstituted immune system generated by transplanting PBMCs through intravenous injection, to evaluate the effect of metformin on tumors.ResultsThe TCGA esophageal cancer data showed that IL-6 expression was positively correlated with PD-L1 expression and that patients with high IL-6 expression had a significantly lower overall survival rate than patients with low IL-6 expression. PD-L1 expression in ESCC cell lines was significantly inhibited by metformin via the IL-6/JAK2/STAT3 signaling pathway but was not correlated with the canonical AMPK pathway. In the coculture system, the metformin pretreatment group showed higher T cell activation and better T cell killing function than the control group. Animal experiments confirmed that metformin downregulated PD-L1 expression and that combination treatment with metformin and PD-1 inhibitors synergistically enhanced the antitumor response.ConclusionsMetformin downregulated PD-L1 expression by blocking the IL-6/JAK2/STAT3 signaling pathway in ESCC, which enhanced the antitumor immune response.

Download Full-text

Abstract 2826: Understanding associations among local microbiome, immune response, and efficacy of immunotherapy in esophageal cancer

10.1158/1538-7445.am2019-2826 ◽

2019 ◽

Cited By ~ 1

Author(s):

Chao Zhang ◽

Prashant V. Thakkar ◽

Prateek Sharma ◽

Sreekar Vennelaganti ◽

Doron Betel ◽

...

Keyword(s):

Immune Response ◽

Esophageal Cancer

Download Full-text

Considerations in Dysphagia Management Following Esophagectomy

Perspectives of the ASHA Special Interest Groups ◽

10.1044/persp1.sig13.169 ◽

2016 ◽

Vol 1 (13) ◽

pp. 169-176

Author(s):

Lisa M. Evangelista ◽

James L. Coyle

Keyword(s):

Esophageal Cancer ◽

Minimally Invasive ◽

Minimally Invasive Surgical Procedures ◽

Esophageal Resection ◽

Minimally Invasive Surgical ◽

Operative Complications ◽

Swallowing Difficulties ◽

Epidemiological Impact ◽

Invasive Techniques ◽

Management Of Dysphagia

Esophageal cancer is the sixth leading cause of death from cancer worldwide. Esophageal resection is the mainstay treatment for cancers of the esophagus. While curative, surgical resection may result in swallowing difficulties that require intervention from speech-language pathologists (SLPs). Minimally invasive surgical procedures for esophageal resection have aimed to reduce morbidity and mortality associated with more invasive techniques. Both intra-operative and post-operative complications, regardless of the surgical approach, can result in dysphagia. This article will review the epidemiological impact of esophageal cancers, operative complications resulting in dysphagia, and clinical assessment and management of dysphagia pertinent to esophageal resection.

Download Full-text