Immunotherapy for esophageal squamous cell carcinoma: a review

Mimura, Kosaku; Yamada, Leo; Ujiie, Daisuke; Hayase, Suguru; Tada, Takeshi; Hanayama, Hiroyuki; Min, Aung Kyi Thar; Shibata, Masahiko; Momma, Tomoyuki; Saze, Zenichiro; Ohki, Shinji; Kono, Koji

doi:10.5387/fms.2018-09

Cited by 39 publications

(30 citation statements)

References 49 publications

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“…The high expression of CD38 has been reported to be a favorable prognosis factor in ESCC [15], prostate cancer [12], hepatic caner [17] and triple negative breast cancer (TNBC) [23]. CD38 participates in the germinal center reaction with inducible co stimulator Ligand competitively and stimulated the anti-tumor immunity [24,25]. Chen et al found no association between CD38 expression and OS in patients with early stage of lung cancer [21].…”

Section: Discussionmentioning

confidence: 99%

High CD38 expression in tumor-infiltrating immune cells is a favorite prognosis factor in esophageal squamous cell carcinoma with perigastric lymph node metastasis

Shi¹,

Xiao²,

Zhao³

et al. 2020

Preprint

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Background The present study aimed to investigate the prognostic effect of CD38 in patients with esophageal squamous cell carcinoma (ESCC). Methods We performed a retrospective cohort study by consecutively recruiting 142 patients with ESCC. The clinicopathological features and expression of CD38, CD4, CD8, Ki-67, PD-L1 and PD-1 in tumor and immune cells were independently evaluated by two pathologists. Results CD38 was expressed in immune cells but not tumor cells and the median expression rate of CD38 in immune cells was 60%. Among ESCC patients with perigastric lymph node metastasis, the expression rate of CD38 was not associated with the disease-free survival (p = 0.207), but had a significant association with the overall survival (p = 0.042). The median overall survival was 13 months and not observed among patients with low and high expression rate of CD38, respectively. The crude and adjusted hazard ratio (HR) of high CD38 expression was 0.37 (95%CI 0.14, 0.95) and 0.21 (95%CI 0.06, 0.70). The expression rate of CD38 had a negative correlation with PD-L1 expressed in tumor cells and CD4 expressed in immune cells. Among patients without perigastric lymph node metastasis, the expression rate of CD38 showed a significant association with the disease-free survival (p < 0.05). The median disease-free survival was 45 months and not achieved for patients with high and low expression of CD38; the adjusted HR of high CD38 expression was 2.13 (95%CI 0.85, 5.33). CD38 did not have significant association with the overall survival for patients without perigastric lymph node metastasis. The expression rate of CD38 had a negative correlation with PD-L1 expressed in tumor cells and a positive correlation with PD-L1 expressed in immune cells. Conclusion The high expression rate of CD38 was associated with a better survival for ESCC with perigastric lymph node metastasis. The prognostic effect of CD38 on esophageal cancer should be warranted in future prospective studies.

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Section: Discussionmentioning

confidence: 99%

High CD38 expression in tumor-infiltrating immune cells is a favorite prognosis factor in esophageal squamous cell carcinoma with perigastric lymph node metastasis

Shi¹,

Xiao²,

Zhao³

et al. 2020

Preprint

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“…In 2015, the incidence and mortality rates of EC were reported to be extremely high, accounting for 25% of the total cancer-related mortality (3). Surgery, medication and radiation therapy are the main treatment options for ESCC; however, survival rates remain poor, rendering further effort for developing new therapeutic strategies necessary (4,5).…”

Section: Introductionmentioning

confidence: 99%

“…The NLRP3 inf lammasome, which could initiate inflammatory responses, is considered to contribute to the SHUANG YU 1 , JIAN-JIAN YIN 1 , JIN-XIN MIAO 2 , SHI-GANG LI 1 , CHEN-ZHENG HUANG 1 , NING HUANG 3 , TIAN-LI FAN 1 , XIANG-NAN LI 4 , YAO-HE WANG 5 , SHENG-NA HAN 1 and LI-RONG ZHANG 1,6 development of cancer-related inflammation and play a crucial role in tumorigenesis (10,11). Recent evidence has also shown that the malignant phenotype of human melanoma, as well as lung and colon carcinoma, are associated with the excessive expression and constitutive activation of the NLRP3 inflammasome (12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Activation of NLRP3 inflammasome promotes the proliferation and migration of esophageal squamous cell carcinoma

Yin

Miao

et al. 2020

Oncol Rep

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Inflammasomes can identify endogenous danger signals as an inflammatory immune response. As the most common inflammasome, the NLR pyrin family domain containing 3 (NLRP3) inflammasome is associated with the pathogenesis of different tumors. However, the function of the NLRP3 inflammasome in esophageal cancer (EC) has rarely been reported. Herein, the expression levels of the components of NLRP3 inflammasome and Ki-67 were analyzed by immunohistochemistry. Furthermore, correlations between the NLRP3 inflammasome and Ki-67 along with the clinicopathological features of EC patients were evaluated. The components of the NLRP3 inflammasome were also assessed by western blot analysis and quantitative PCR. NLRP3 was silenced or overexpressed in different esophageal squamous cell carcinoma (ESCC) cell lines, and cell viability, migration and invasion were assessed by CCK-8 and Transwell assays. The present results showed that high NLRP3 expression in the tumor specimens was significantly associated with TNM stage and T category. Spearman's correlation analysis revealed a positive correlation between NLRP3 and the Ki-67 proliferation index. The mRNA and protein levels of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), cleaved caspase-1, and interleukin (IL)-1β in tumor tissues were higher than those in non-cancerous tissues. The level of secreted IL-1β in tumor tissues was also increased, as compared to that in normal tissues. Silencing of NLRP3 in KYSE-70 and TE13 cells strongly attenuated cell viability, decreased cell mobility in wound-healing assays and greatly diminished the ability of cell migration and invasion in the Transwell system. Overexpression of NLRP3 in KYSE-510 and EC9706 cells markedly promoted the proliferation, migration and invasion. Collectively, these results revealed that the the NLRP3 inflammasome is upregulated in human ESCC tissues and promotes ESCC progression. Hence, NLRP3 could be a promising new candidate diagnostic and prognostic target.

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“…1 Squamous cell carcinoma and adenocarcinoma are the two predominant histologic subtypes of esophageal cancer, with the former accounting for >90% of all cases of esophageal cancer. 1,2 Although the 5-year global survival rate of esophageal squamous cell carcinoma (ESCC) patients (30-40%) has improved due to the advancements in diagnostic and treatment modalities, the cancer is still detected in advanced stages in many patients and the efficacy of current systematic treatments, especially chemotherapy, remains unsatisfactory. 2,3 Therefore, developing novel therapeutic strategies and agents remains an urgent need for ESCC therapy.…”

Section: Introductionmentioning

confidence: 99%

<p>AR-42: A Pan-HDAC Inhibitor with Antitumor and Antiangiogenic Activities in Esophageal Squamous Cell Carcinoma</p>

Zhu¹,

Yuan²,

Zhang³

et al. 2019

DDDT

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Esophageal squamous cell carcinoma (ESCC) is a refractory malignancy with high morbidity and mortality. Thus, there is an urgent need to find effective targets and agents for ESCC treatment. The purpose of this study was to assess the anti-ESCC effects of a pan-histone deacetylase (HDAC) inhibitor AR-42 and its mechanisms of action. Methods: Immunohistochemical staining was performed to detect HDAC1 expression in ESCC and adjacent tissue samples. MTT assay, Edu cell proliferation test, flow cytometry, and subcutaneous xenograft were used to assess the anti-ESCC effects of AR-42; furthermore, the antiangiogenic activity of AR-42 was evaluated using endothelial cell migration, invasion, and tube formation assays as well as zebrafish angiogenesis assay. Western blot analysis was performed to explore the underlying mechanism of the anti-ESCC activity of AR-42. Results: HDAC1-positive expression was much higher in ESCC cells than in paracancerous tissues, and the elevated HDAC1 expression was a strong indicator of lymph node metastasis and a more advanced TNM stage of ESCC. Moreover, AR-42 potently suppressed ESCC cell growth through cellular proliferation inhibition and apoptosis induction. Moreover, AR-42 displayed a moderate antiangiogenic activity, and it could significantly inhibit the migration, invasion and tubulogenesis of human umbilical vein endothelial cells as well as intersegmental vessel formation in zebrafish at micromolar concentrations. More importantly, the inhibitory activity of AR-42 on ESCC cells and angiogenesis could also be observed in the TE-1 xenograft model. Further studies showed that AR-42 exerts its anti-ESCC effects mainly by upregulating the expression of p21 and blocking the transduction of multiple signaling cascades related to tumor growth, especially Stat3-mediated signaling. Conclusion: Overall, AR-42 has significant potency for inhibiting ESCC cell growth and shows moderate effect in suppressing angiogenesis, displaying strong anti-ESCC effects in vitro and in vivo. Thus, AR-42 deserves further evaluation as a potential candidate for ESCC therapy.

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Immunotherapy for esophageal squamous cell carcinoma: a review

Cited by 39 publications

References 49 publications

High CD38 expression in tumor-infiltrating immune cells is a favorite prognosis factor in esophageal squamous cell carcinoma with perigastric lymph node metastasis

High CD38 expression in tumor-infiltrating immune cells is a favorite prognosis factor in esophageal squamous cell carcinoma with perigastric lymph node metastasis

Activation of NLRP3 inflammasome promotes the proliferation and migration of esophageal squamous cell carcinoma

<p>AR-42: A Pan-HDAC Inhibitor with Antitumor and Antiangiogenic Activities in Esophageal Squamous Cell Carcinoma</p>

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