scholarly journals Immunosuppressive phenotype of esophagus tumors stroma

2020 ◽  
Author(s):  
Alexei Gratchev ◽  
Olga V. Kovaleva ◽  
Madina A. Rashidova ◽  
Daria V. Samoilova ◽  
Valeria V. Mochalnikova

Abstract Background Tumor associated macrophages and tumor infiltrating lymphocytes contribute significantly to the development of immunosuppressive properties of tumor. In this study we performed immunohistochemical analysis of immune cells of esophageal tumors stroma. Methods Paraffin‑embedded tissue specimens from 48 esophageal squamous cell carcinoma patients were retrospectively collected for immunohistochemical analysis of stromal cells. For staining of macrophages, CD68, CD163, CD206, PU.1 and iNOS were used. For T-cells detection CD8, CD3, FOXP3 were used. As well we performed staining for PD-L1 that can be expressed on tumor associated macrophagesand tumor cells. Clinicopathological and survival data were collected and analyzed using the χ2 and Fisher exact tests, Kaplan–Meier curves, and the log‑rank test. The correlation analysis was performed with Spearman correlation coefficient. Results The level of CD206 expression was associated with histological grade (p = 0.034), FOXP3 expression was associated with sex and age (p = 0.041, p = 0.003 respectively) and iNOS expression was associated with the disease stage (p = 0.044). In addition, FOXP3 and CD163 appeared to be markers of good prognosis (HR = 0.5407, p = 0.0462; HR = 0.4447, p = 0.0456 respectively). Significant association between PU.1 + and CD68 + macrophages (r = 0.752; P = 0.000) and between PU.1 + and CD163 + macrophages (r = 0.585; P = 0.000) was established, positive association between PU.1 and CD206 expression was also observed (r = 0.424; P = 0.001). Conclusions Large amounts of CD163 + macrophages and FOXP3+ Т-cells appear to be markers of good prognosis of esophageal squamous cell carcinoma. The number of PU.1 + macrophages strongly correlate with the number of CD68 + macrophages therefore usage of PU.1 as a potential macrophage marker can be recommended esophageal tumors.

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Olga V. Kovaleva ◽  
Madina A. Rashidova ◽  
Daria V. Samoilova ◽  
Polina A. Podlesnaya ◽  
Valeria V. Mochalnikova ◽  
...  

Background. Tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs) contribute significantly to the development of immunosuppressive properties of a tumor. In this study, we performed immunohistochemical analysis of immune cells of esophageal tumors stroma. Methods. Paraffin-embedded tissue specimens from 48 esophageal squamous cell carcinoma (ESCC) patients were retrospectively collected for immunohistochemical analysis of stromal cells. For staining of macrophages, CD68, CD163, CD206, PU.1, and iNOS were used. For T cell detection, CD8, CD3, and FOXP3 were used. Also, we performed staining for PD-L1 that can be expressed on TAMs and tumor cells. Clinicopathological and survival data were collected and analyzed using the χ2 and Fisher exact tests, Kaplan–Meier curves, and the log-rank test. The correlation analysis was performed with Spearman’s rank correlation coefficient. Results. We found that FOXP3 expression was associated with age (p=0.042) and iNOS expression was associated with the disease stage (p=0.044). In addition, FOXP3 and CD163 appeared to be markers of good prognosis (HR=0.4420, p=0.0325, and HR=0.4447, p=0.0456, respectively). Significant association between PU.1+ and CD68+ macrophages (r=0.833; p≤0.001) and between PU.1+ and CD163+ macrophages (r=0.500; p≤0.001) was established; positive association between PU.1 and CD206 expression was also observed (r=0.250; p=0.043). Conclusions. Large amounts of CD163+ macrophages and FOXP3+ Т cells appear to be markers of good prognosis of ESCC. The number of PU.1+ macrophages strongly correlates with the number of CD68+ macrophages; therefore, usage of PU.1 as a potential macrophage marker can be recommended for esophageal tumors.


2018 ◽  
Vol 9 (11) ◽  
Author(s):  
Yan-Fen Feng ◽  
Yi-Yan Lei ◽  
Jia-Bin Lu ◽  
Shao-Yan Xi ◽  
Yu Zhang ◽  
...  

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Xue-feng Leng ◽  
Wenwu He ◽  
Xuefeng Leng ◽  
Qiyu Luo ◽  
Tianqin Mao ◽  
...  

Abstract   Lymph node(LN)metastasis is a common metastasis mode of esophageal squamous cell carcinoma (ESCC). The purpose of this study is to explore whether recurrent laryngeal nerve LNs metastasis can be used as a predictor of cervical LN dissection. Methods The postoperative pathological examination results of patients with ESCC who underwent three-field LN dissection in Sichuan Cancer Hospital from January 2010 to January 2016 were retrospectively collected to explore the relationship between the recurrent laryngeal nerve LN metastasis and cervical LN metastasis. At the same time, analyzed survival data to determine whether cervical LN dissection should be performed on patients with thoracic ESCC. Results Among all the study subjects, 53.3% (72/135) patients had metastasis in the thoracic recurrent laryngeal nerve LNs, and 36.3% (49/135) patients had metastasis in the cervical LN. 44.4% (32/72) Patients with metastasis in the thoracic recurrent laryngeal nerve LN tended to have a high incidence of cervical LN metastasis (P = 0.035). Subgroup analysis showed that 60% (81/135) patients had upper thoracic ESCC, and 46.9% (38/81) patients had cervical LN metastasis (P = 0.002). Survival analysis showed that patients with cervical LN metastasis had poor survival (P < 0.001). Multivariate analysis showed that bilateral recurrent laryngeal nerve LN metastasis was an independent risk factor for survial(P = 0.029). Conclusion Patients with bilateral recurrent laryngeal nerve LN metastasis in upper thoracic ESCC can be used as a predictor of cervical LN dissection.


2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Ming He ◽  
Zhan Qi ◽  
Rong Qiu ◽  
Yuanping Hu ◽  
Juan Li ◽  
...  

Esophageal squamous cell carcinoma (ESCC) is the most common pathological type of esophageal cancer in China. Patients with ESCC have poor long-term survival, especially those with lymphatic metastasis (pN + ESCC). In this retrospective study, we evaluated the correlates of long-term survival time of patients with pN + ESCC. A total of 453 patients with pN + ESCC who underwent surgical R0 resection between Jan 2008 and Sep 2011 were enrolled. The follow-up ended on December 2019. The clinical, pathological, inflammation-related factors and general survival data of these patients were analyzed using SPSS 22.0 software. The 1-, 3-, and 5-year overall survival (OS) rates were 73.7%, 34.6%, and 25.6%, respectively; the 1-, 3-, and 5-year disease-free survival (DFS) rates were 45.0%, 26.3%, and 20.4%, respectively. The median OS and DFS were 23 and 14 months, respectively. On multivariate analyses, gender, site of lesion, number of dissected lymph nodes, stage pTNM, adjuvant therapy, and neutrophil lymphocyte ratio were independent predictors of OS. Site of lesion, stage pTNM, and adjuvant therapy were independent predictors of DFS. Recursive partitioning analysis (RPA) scores of each patient were calculated based on the independent predictors of OS, and the patients were divided into 3 classes: low-risk, medium-risk, and high-risk. The OS, DFS, and local recurrence-free survival were significantly different among these three RPA classes P < 0.001 . Several factors showed an independent association with long-term postoperative survival of pN + ESCC patients after radical surgery. RPA scores can potentially be used to predict the prognosis of ESCC.


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 70-70
Author(s):  
Yuta Maruki ◽  
Atsuo Takashima ◽  
Takahiro Miyamoto ◽  
Hidekazu Hirano ◽  
Hirokazu Shoji ◽  
...  

70 Background: B7-H3 (also known as CD276) belongs to a family of immune modulators that includes PD-1 and PD-L1 (also known as B7-H1 or CD274), which has been reported to be expressed in many carcinomas and associated with poor prognosis. In this study, we explored the relationship between B7-H3 expression and clinical background and prognosis of esophageal squamous cell carcinoma (ESCC) patients treated with surgery alone. Methods: The subjects of this study was the ESCC patients who received curative surgery between January 2009 and December 2014 without prior treatment, excluding T4 and M1 disease. We evaluated tumor B7-H3 expression by immunohistochemistry, which was scored to 0 (absent) if < 10% of cancer cells were stained, and 1 (weak), 2 (moderate), or 3 (strong) according to the intensity in stained cancer cells (> 10%). The B7-H3 expression of score 2 and 3 was regarded as positive. We compared the clinical characteristics and prognosis between B7-H3 positive and negative patients using log rank test and Cox proportional hazards regression analysis for adjusting the backgrounds. Results: 33 (45%) of 74 patients were positive for expression of B7-H3. Between H7-H3 (+) and (-) groups, there were difference in pathological T stage (pT1/pT2/pT3: 9/0/24 vs. 23/4/14, p < 0.01) and lymph vessel invasion (+/-: 7/26 vs. 17/24, p=0.08). There was no association between sex, age, N factor, and vascular invasion. B7-H3 (+) patients showed trend of poor recurrence free survival (RFS) and overall survival, not significant, (HR=1.41[95%CI:0.63-3.14] p=0.41 for RFS, HR=1.34[ 95%CI:0.52-3.48] p=0.55 for OS). However B7-H3 status was not a prognostic factor in multivariate analysis (HR=0.78[95% CI: 0.33-1.85] for RFS, HR=0.73 [ 95%CI:0.26-2.02] for OS). Conclusions: The expression ratio of B7-H3 was observed in 45% of the esophageal cancer, which was related with T stage and lymphatic vessel invasion but not with clinical outcomes such as RFS and OS.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15589-e15589
Author(s):  
Honghai Dai ◽  
Yang Shao ◽  
Xiaoling Tong ◽  
Xue Wu ◽  
Jiaohui Pang ◽  
...  

e15589 Background: Definitive concurrent chemoradiation therapy (dCRT) is the standard treatment for patients with nonsurgical esophageal squamous cell carcinoma (ESCC), yet patients demonstrated great variations in responses and post-treatment progression inevitably. Methods: To identify prognostic factors that could assist in clinical judgment and make predictions ahead of disease relapse, we performed a targeted next generation sequencing of 416 cancer-related genes on primary tumor biopsies from 47 ESCC patients with locally advanced or metastatic nonsurgical diseases. Patients were subjected to dCRT treatment and local recurrence free survival (LRFS), progression free survival (PFS) and overall survival (OS) times were analyzed. Results: TP53 (78%), NOTCH1 (32%), ARID1A (13%), FAT1 (13%) and CDKN2A (13%) are the most commonly mutated genes in ESCC, while copy number gains are frequently occurred in MCL1 (36%), FGF19 (34%), MYC (32%), CCND1 (27%), ZNF217 (15%), CDKN2A (13%) and YAP1 (11%). Multivariate analysis including clinical variables (age, gender and disease stage) and individual genetic alterations suggested that gender is an independent prognostic factor and male tend to have longer LRFS, PFS and OS after dCRT treatment. In addition, YAP1 amplification likely increased the risk of disease progression and death. To remove the impact of gender on prognosis, gender stratified survival analysis was performed and found that male patients with YAP1 amplification had significantly shorter LRFS (p = 0.002) and OS (p = 0.03), and also demonstrated a certain trend toward a shorter PFS (p = 0.06) than male patients without YAP1 amplification. Conclusions: YAP1 amplification might be a potentially useful biomarker in predicting treatment outcomes and selecting patients with high relapse risk for closely monitoring.


2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Atsushi Shiozaki ◽  
Kenichi Takemoto ◽  
Daisuke Ichikawa ◽  
Hitoshi Fujiwara ◽  
Hirotaka Konishi ◽  
...  

The objectives of the present study were to investigate the role of K–Cl cotransporter 3 (KCC3) in the regulation of cellular invasion and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC). Immunohistochemical analysis performed on 70 primary tumor samples obtained from ESCC patients showed that KCC3 was primarily found in the cytoplasm of carcinoma cells. Although the expression of KCC3 in the main tumor (MT) was related to several clinicopathological features, such as the pT and pN categories, it had no prognostic impact. KCC3 expression scores were compared between the MT and cancer nest (CN), and the survival rate of patients with aCN>MTscore was lower than that of patients with aCN≤MTscore. In addition, the survival rate of patients in whom KCC3 was expressed in the invasive front of tumor was lower than that of the patients without it. Furthermore, multivariate analysis demonstrated that the expression of KCC3 in the invasive front was one of the most important independent prognostic factors. The depletion of KCC3 using siRNAs inhibited cell migration and invasion in human ESCC cell lines. These results suggest that the expression of KCC3 in ESCC may affect cellular invasion and be related to a worse prognosis in patients with ESCC.


2009 ◽  
Vol 22 (6) ◽  
pp. 496-504 ◽  
Author(s):  
J. Boone ◽  
R. van Hillegersberg ◽  
G. J. A. Offerhaus ◽  
P. J. van Diest ◽  
I. H. M. Borel Rinkes ◽  
...  

2018 ◽  
Vol 48 (1) ◽  
pp. 251-262 ◽  
Author(s):  
Xian-Zi Yang ◽  
Qing-Jun He ◽  
Tian-Tian Cheng ◽  
Jun Chi ◽  
Zi-Ying Lei ◽  
...  

Background/Aims: Considerable evidence indicates that long noncoding RNAs (lncRNAs) exert importantly regulatory functions during human cancer initiation and progression and are promising biotargets in the flight against cancer. Methods: In this study, we evaluated the role of the lncRNA LINC01133 in esophageal squamous cell carcinoma (ESCC). LINC01133 expression in ESCC was examined by quantitative real-time PCR. The correlations between LINC01133 expression and clinicopathological variables and survival were examined by the χ2 test, Kaplan–Meier method, log-rank test, and univariate Cox regression analysis. Results: LINC01133 expression levels were frequently lower in ESCC tissues and cell lines than in paired normal tissues and an immortalized esophageal epithelial cell line, respectively. The expression of LINC01133 decreased in a TNM stage- and lifestyle-independent manner. LINC01133 was an independent protective factor and had an anti-tumor effect in the early stage of ESCC development. More importantly, we discovered that drinking status in our cohort impaired the predictive accuracy of LINC01133 for patients with ESCC. Furthermore, a new risk model combining LINC01133 expression, drinking status, and TNM stage provided better survival discrimination compared with three other predictors. Conclusions: Our data indicate that a loss of LINC01133 expression is a potential poor prognostic biomarker and therapeutic target for ESCC and provide additional prognostic information to improve the outcomes of ESCC patients.


2021 ◽  
Vol 27 ◽  
Author(s):  
Yibo Guo ◽  
Yiwen Liu ◽  
Haijun Yang ◽  
Ningtao Dai ◽  
Fuyou Zhou ◽  
...  

Purpose: The present study focused on exploring the associations of Porphyromonas gingivalis (P. gingivalis) infection and low Beclin1 expression with clinicopathological parameters and survival of esophageal squamous cell carcinoma (ESCC) patients, so as to illustrate its clinical significance and prognostic value.Methods: Immunohistochemistry (IHC) was used to detect P. gingivalis infection status and Beclin1 expression in 370 ESCC patients. The chi-square test was adopted to illustrate the relationship between categorical variables, and Cohen’s kappa coefficient was used for correlation analysis. Kaplan-Meier survival curves with the log-rank test were used to analyse the correlation of P. gingivalis infection and low Beclin1 expression with survival time. The effects of P. gingivalis infection and Beclin1 downregulation on the proliferation, migration and antiapoptotic abilities of ESCC cells in vitro were detected by Cell Counting Kit-8, wound healing and flow cytometry assays. For P. gingivalis infection of ESCC cells, cell culture medium was replaced with antibiotic-free medium when the density of ESCC cells was 70–80%, cells were inoculated with P. gingivalis at a multiplicity of infection (MOI) of 10.Result:P. gingivalis infection was negatively correlated with Beclin1 expression in ESCC tissues, and P. gingivalis infection and low Beclin1 expression were associated with differentiation status, tumor invasion depth, lymph node metastasis, clinical stage and prognosis in ESCC patients. In vitro experiments confirmed that P. gingivalis infection and Beclin1 downregulation potentiate the proliferation, migration and antiapoptotic abilities of ESCC cells (KYSE150 and KYSE30). Our results provide evidence that P. gingivalis infection and low Beclin1 expression were associated with the development and progression of ESCC.Conclusion: Long-term smoking and alcohol consumption causes poor oral and esophageal microenvironments and ESCC patients with these features were more susceptible to P. gingivalis infection and persistent colonization, and exhibited lower Beclin1 expression, worse prognosis and more advanced clinicopathological features. Our findings indicate that effectively eliminating P. gingivalis colonization and restoring Beclin1 expression in ESCC patients may contribute to preventation and targeted treatment, and yield new insights into the aetiological research on ESCC.


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