A high number of stromal tumor-infiltrating lymphocytes is a favorable independent prognostic factor in M0 (stages I-III) esophageal squamous cell carcinoma

2016 ◽  
Author(s):  
Jing Li ◽  
Yang Tang ◽  
Liu Huang ◽  
Qianqian Yu ◽  
Guangyuan Hu ◽  
...  
Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4473
Author(s):  
Takuro Yamauchi ◽  
Fumiyoshi Fujishima ◽  
Masatoshi Hashimoto ◽  
Junichi Tsunokake ◽  
Ryujiro Akaishi ◽  
...  

Necroptosis is a pivotal process in cancer biology; however, the clinical significance of necroptosis in esophageal squamous cell carcinoma (ESCC) has remained unknown. Therefore, in this study, we aimed to verify the potential involvement of necroptosis in the clinical outcome, chemotherapeutic resistance, and tumor microenvironment of ESCC. Mixed lineage kinase domain-like protein (MLKL) and phosphorylated MLKL (pMLKL) were immunohistochemically examined in 88 surgically resected specimens following neoadjuvant chemotherapy (NAC) and 53 pre-therapeutic biopsy specimens, respectively. Tumor-infiltrating lymphocytes (TILs) were also evaluated by immunolocalizing CD3, CD8, and forkhead box protein 3 (FOXP3) in the residual tumors after NAC. High pMLKL status in the post-NAC resected specimens was significantly correlated with worse prognosis in ESCC patients. Multivariate analysis demonstrated that a high pMLKL status was an independent prognostic factor. In pre-NAC biopsy specimens, a high pMLKL status was significantly associated with a lower therapeutic efficacy. CD8+ TILs were significantly lower in the high-pMLKL group. FOXP3+ TILs were significantly higher in both high-MLKL and high-pMLKL groups. We first demonstrated pMLKL status as an independent prognostic factor in ESCC patients. Our study revealed the possible involvement of necroptosis in the immunosuppressive microenvironment, resulting in the attenuated therapeutic efficacy of NAC and eventual adverse clinical outcomes in ESCC.


2005 ◽  
Vol 65 (11) ◽  
pp. 4963-4968 ◽  
Author(s):  
Diana L. Mandelker ◽  
Keishi Yamashita ◽  
Yutaka Tokumaru ◽  
Koshi Mimori ◽  
David L. Howard ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3982
Author(s):  
Yen-Hao Chen ◽  
Hung-I Lu ◽  
Chien-Ming Lo ◽  
Shau-Hsuan Li

Cluster of differentiation (CD)-73 plays pivotal roles in the regulation of immune reactions via the production of extracellular adenosine, and the overexpression of CD73 is associated with worse outcomes in several types of cancers. Here, we identified 167 esophageal squamous cell carcinoma (ESCC) patients who underwent esophagectomy, including 64 and 103 patients with high and low expression levels of CD73, respectively. Univariate and multivariate analyses showed high expression of CD73 was an independent prognostic factor for worse disease-free survival and overall survival. In addition, we selected another cohort consisting of 38 ESCC patients receiving nivolumab or pembrolizumab and found that treatment response and survival benefit to immunotherapy were strongly correlated with the expression levels of CD73/programmed death ligand 1. Moreover, the transwell assay revealed knockdown of CD73 in two ESCC cell lines, TE1 and KYSE30, exhibited significantly reduced abilities of cell invasion and migration. CD73 silencing also showed that the protein expression levels of CD73, vimentin, and snail were downregulated, while those of E-cadherin were upregulated in Western blotting. The findings of our study indicate CD73 may be an independent prognostic factor for ESCC patients who underwent esophagectomy. Furthermore, it may be associated with the patient responses to immunotherapy.


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