Necroptosis in Esophageal Squamous Cell Carcinoma: An Independent Prognostic Factor and Its Correlation with Tumor-Infiltrating Lymphocytes
| Autor: | Fumiyoshi Fujishima, Ryujiro Akaishi, Yusuke Gokon, Yohei Ozawa, Takashi Kamei, Masatoshi Hashimoto, Yusuke Taniyama, Tomohiro Nakamura, Naoki Nakaya, Hironobu Sasano, Takuro Yamauchi, Chiaki Sato, Shunsuke Ueki, Junichi Tsunokake, Toshiaki Fukutomi, Hiroshi Okamoto |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
Tumor microenvironment biology medicine.diagnostic_test Tumor-infiltrating lymphocytes business.industry CD3 Necroptosis phosphorylated mixed lineage kinase domain-like protein FOXP3 necroptosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens mixed lineage kinase domain-like protein Article esophageal squamous cell carcinoma Oncology Biopsy Cancer research biology.protein medicine Clinical significance business CD8 RC254-282 neoadjuvant chemotherapy |
| Zdroj: | Cancers, Vol 13, Iss 4473, p 4473 (2021) Cancers Volume 13 Issue 17 |
| ISSN: | 2072-6694 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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