Immune checkpoint blockade therapy for esophageal squamous cell carcinoma

Harada, Kazuto; Kaya, Dılşa Mızrak; Baba, Hideo; Ajani, Jaffer A.

doi:10.21037/jtd.2018.01.120

Cited by 5 publications

(4 citation statements)

References 20 publications

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“…The mutations or epigenetic inactivation of the mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2 could cause microsatellite instability (MSI), which means that the microsatellite sequences of DNA cannot be repaired，resulting in a replication error. Tumor mutation burden is related to MSI and they both have reliable predictive and prognostic value . High TMB means that more new antigens are exposed to the body's immune system, which can better activate the immune system and make ICIs treatment more effective, which has been verified in metastatic colorectal cancer .…”

Section: How To Screen the Patients Who Can Benefit From Immunotherapy?mentioning

confidence: 99%

“…Tumor mutation burden is related to MSI and they both have reliable predictive and prognostic value. 63 High TMB means that more new antigens are exposed to the body's immune system, which can better activate the immune system and make ICIs treatment more effective, which has been verified in metastatic colorectal cancer. 64 It has been reported that esophageal cancer is a tumor with a high mutation load.…”

Section: Patients Who Can Benefit From Immunotherapy?mentioning

confidence: 99%

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A good start of immunotherapy in esophageal cancer

Zhao

Meng

2019

Cancer Medicine

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Considering the benefits of immunotherapy in advanced melanoma, non–small cell lung cancer, renal cell carcinoma, bladder cancers, and refractory Hodgkin lymphoma, we begin to consider whether immunotherapy is effective for esophageal cancer, which is extremely malignant and has a poor prognosis. There are a large number of clinical trials to study the application of immunotherapy such as immune checkpoint inhibitors, peptide vaccine, adoptive T cell transfer and oncolytic virus in esophageal cancer. Some already have preliminary results and show the advantages of immunotherapy in esophageal cancer, while others are still in progress. This review aims to introduce the feasibility and current status of immunotherapy in esophageal cancer.

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Section: How To Screen the Patients Who Can Benefit From Immunotherapy?mentioning

confidence: 99%

Section: Patients Who Can Benefit From Immunotherapy?mentioning

confidence: 99%

A good start of immunotherapy in esophageal cancer

Zhao

Meng

2019

Cancer Medicine

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“…2 , 3 The limited improvement in treatment outcome by conventional therapies has prompted the search for innovative strategies for the treatment of oesophageal cancer, especially immunotherapeutically targeted treatments. 4 , 5 …”

Section: Introductionmentioning

confidence: 99%

Prognostic and clinical impact of PD-L2 and PD-L1 expression in a cohort of 437 oesophageal cancers

et al. 2020

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Background The PD-1/PD-L1 pathway plays critical roles in tumour immunology, and serves as an immune-based therapeutic target. Less is known regarding PD-L2, another ligand of PD-1, and its relation to clinical outcome in human cancers. Methods We used a database of 437 surgically and 100 endoscopically resected oesophageal cancers (squamous cell carcinoma, n = 483; adenocarcinoma, n = 36; others, n = 18) to evaluate PD-L2 and PD-L1 expression by immunohistochemistry. Results Compared with PD-L2-negative cases (n = 366, 83.8%), PD-L2-positive cases (n = 71, 16.2%) had worse overall survival (P = 0.011, log-rank test). There was not a significant correlation between PD-L2 and PD-L1 expression. Multiplex immunofluorescence revealed that there was variability in the expression pattern of PD-L2 and PD-L1. In early-stage tumours, PD-L2 expression was more frequently observed compared with PD-L1. Conclusions PD-L2 as well as PD-L1 were associated with an unfavourable prognosis in oesophageal cancer, supporting the role of PD-L2 as a prognostic biomarker. Considering that PD-L2 and PD-L1 had different features in terms of expression timing and responses to chemotherapeutic drugs, evaluation of both PD-L2 and PD-L1 expression may be clinically important.

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“…The combination of two or more drugs has a more marked reaction, as it has been reported to increase the efficacy of chemoradiotherapy in patients with ESCA ( 8 - 10 ). However, intolerance of fluoropyrimidine-based, platinum-based and taxane-based chemotherapy has also been identified in patients, and immune checkpoint blockade therapy remains under investigation ( 11 ). Therefore, further research is required for more effective therapeutic methods.…”

Section: Introductionmentioning

confidence: 99%

Novel drug candidates for treating esophageal carcinoma: A study on differentially expressed genes, using connectivity mapping and molecular docking

et al. 2018

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Patients with esophageal carcinoma (ESCA) have a poor prognosis and high mortality rate. Although standard therapies have had effect, there is an urgent requirement to develop novel options, as increasing drug tolerance has been identified in clinical practice. In the present study, differentially expressed genes (DEGs) of ESCA were identified in The Cancer Genome Atlas and Genotype-Tissue Expression databases. Functional and protein-protein interaction (PPI) analyses were performed. The Connectivity Map (CMAP) was selected to predict drugs for the treatment of ESCA, and their target genes were acquired from the Search Tool for Interactions of Chemicals (STITCH) by uploading the Simplified Molecular-Input Line-Entry System structure. Additionally, significant target genes and ESCA-associated hub genes were extracted using another PPI analysis, and the corresponding drugs were added to construct a network. Furthermore, the binding affinity between predicted drug candidates and ESCA-associated hub genes was calculated using molecular docking. Finally, 827 DEGs (|log2 fold-change|≥2; q-value <0.05), which are principally involved in protein digestion and absorption (P<0.005), the plasminogen-activating cascade (P<0.01), as well as the ‘biological regulation’ of the Biological Process, ‘membrane’ of the Cellular Component and ‘protein binding’ of the Molecular Function categories, were obtained. Additionally, 11 hub genes were obtained from the PPI network (all degrees ≥30). Furthermore, the 15 first screen drugs were extracted from CMAP (score <−0.85) and the 9 second screen drugs with 70 target genes were extracted from STITCH. Furthermore, another PPI analysis extracted 51 genes, and apigenin, baclofen, Prestwick-685, menadione, butyl hydroxybenzoate, gliclazide and valproate were selected as drug candidates for ESCA. Those molecular docking results with a docking score of >5.52 indicated the significance of apigenin, Prestwick-685 and menadione. The results of the present study may lead to novel drug candidates for ESCA, among which Prestwick-685 and menadione were identified to be significant new drug candidates.

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Immune checkpoint blockade therapy for esophageal squamous cell carcinoma

Cited by 5 publications

References 20 publications

A good start of immunotherapy in esophageal cancer

A good start of immunotherapy in esophageal cancer

Prognostic and clinical impact of PD-L2 and PD-L1 expression in a cohort of 437 oesophageal cancers

Novel drug candidates for treating esophageal carcinoma: A study on differentially expressed genes, using connectivity mapping and molecular docking

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