Immune signature profiling identified predictive and prognostic factors for esophageal squamous cell carcinoma

Li, Yuan; Lu, Zhiliang; Cao, Yun; Wang, Jingnan; Sun, Shengrong; Huang, Jianbing; Mao, Shuangshuang; Lei, Yuanyuan; Chen, Zhaoli; He, Jie

doi:10.1080/2162402x.2017.1356147

Cited by 70 publications

(78 citation statements)

References 44 publications

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“…In addition to its effects on immunotherapy, TME influences the efficiency of chemotherapy and radiotherapy through preexisting TME properties and therapy‐induced responses in TME 9 . Infiltrating numbers of T cells, macrophages, and cancer‐associated fibroblasts in the TME are associated with patient outcomes in various cancers, including lung cancer, urothelial cancer, and esophageal cancer 10‐12 . Therefore, characterization of the TME facilitates the development of prognostic and predictive biomarkers and the identification of novel therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

Tumor microenvironment characterization identifies two lung adenocarcinoma subtypes with specific immune and metabolic state

Huang

Zheng

et al. 2020

Cancer Science

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The tumor microenvironment (TME) is a vital component of tumor tissue. Increasing evidence suggests their significance in predicting outcomes and guiding therapies. However, no studies have reported a systematic analysis of the clinicopathologic significance of TME in lung adenocarcinoma (LUAD). Here, we inferred tumor stromal cells in 1184 LUAD patients using computational algorithms based on bulk tumor expression data, and evaluated the clinicopathologic significance of stromal cells. We found LUAD patients showed heterogeneous abundance in stromal cells. Infiltration of stromal cells was influenced by clinicopathologic features, such as age, gender, smoking, and TNM stage. By clustering stromal cells, we identified 2 clinically and molecularly distinct LUAD subtypes with immune active and immune repressed features. The immune active subtype is characterized by repressed metabolism and repressed proliferation of tumor cells, while the immune repressed subtype is characterized by active metabolism and active proliferation of tumor cells. Differentially expressed gene analysis of the two LUAD subtypes identified an immune activation signature. To diagnose TME subtypes practically, we constructed a TME score using principal component analysis based on the immune activation signature. The TME score predicted TME subtypes effectively in 3 independent datasets with areas under the receiver operating characteristic curves of 0.960, 0.812, and 0.819, respectively. In conclusion, we proposed 2 clinically and molecularly distinct LUAD subtypes based on tumor microenvironment that could be valuable in predicting clinical outcome and guiding immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Tumor microenvironment characterization identifies two lung adenocarcinoma subtypes with specific immune and metabolic state

Huang

Zheng

et al. 2020

Cancer Science

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“…It has been previously reported that CD38 promoted ESCC cell growth by suppressing MDCS and the monoclonal antibody Daratumumab against CD38 reduced the growth of esophageal tumors in vivo [14]. However, results from Li's study showed that the expression of CD38 was a favorable predictor for ESCC patients [15], and the study pooled all ESCC patients together including both early stage patients and patients with lymph node metastasis. In our study, the signi cantly prognostic effect of CD38 expression was only observed in ESCC patients with perigastric lymph node metastasis.…”

Section: Discussionmentioning

confidence: 96%

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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“…12 IL-1RN was confirmed to be downregulated in ESCC. 13 However, the mechanism and function of IL-1RA remains unclear. which was multiplied by the staining intensity (0, no staining; 1, weak staining, light yellow; 2, moderate staining, yellow-brown; and 3, strong staining, brown) to obtain a score ranging from 0 to 12.…”

Section: Vegf Vascular Endothelial Growth Factormentioning

confidence: 99%

“…Downregulation of IL‐1RA is correlated with the metastatic potential of gastric cancer through blockage of the IL‐1α/VEGF signaling pathways . IL‐1RN was confirmed to be downregulated in ESCC . However, the mechanism and function of IL‐1RA remains unclear.…”

Section: Introductionmentioning

confidence: 99%

IL‐1RA suppresses esophageal cancer cell growth by blocking IL‐1α

Chen

Shen

Liu

et al. 2019

Clinical Laboratory Analysis

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BackgroundInterleukin‐1 promotes tumor angiogenesis through VEGF production. The interleukin‐1 receptor antagonist can suppress tumors by blocking this effect.MethodsImmunohistochemistry, WB, and gene sequencing were used to analyze the expression of IL‐1RA in esophageal cancer patients. WB was used to detect the expression of IL‐1RA and interleukin‐1α in esophageal cancer cells. Stable ESCC cell models overexpressing the IL‐1RA were constructed. Their cell functions were tested, and their effects on VEGF were examined.ResultsIL‐1RA is downregulated in primary EC tumors, and this downregulation of IL‐1RA is closely related to TNM staging and survival prognosis. The overexpression of IL‐1RA increased the proliferation of KYSE410 EC cells, which have a high level of IL‐1α expression. Overexpression of IL‐1RA in KYSE410 cells promotes a decrease in the expression of VEGF‐A. However, IL‐1RA expression did not cause any changes in EC9706 cells with low IL‐1α expression.ConclusionIL‐1RA acts as a tumor suppressor, and its deletion promotes tumor progression by increasing VEGF‐A expression in ESCC.

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Immune signature profiling identified predictive and prognostic factors for esophageal squamous cell carcinoma

Cited by 70 publications

References 44 publications

Tumor microenvironment characterization identifies two lung adenocarcinoma subtypes with specific immune and metabolic state

Tumor microenvironment characterization identifies two lung adenocarcinoma subtypes with specific immune and metabolic state

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

IL‐1RA suppresses esophageal cancer cell growth by blocking IL‐1α

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