Cytotoxic T lymphocyte antigen-4 expression in esophageal carcinoma: implications for prognosis

Zhang, Xiao Fei; Pan, Ke; Weng, De Sheng; Chen, Chang Long; Wang, Qi Jing; Zhao, Jing; Pan, Qiu Zhong; Liu, Qing; Jiang, Shan; Li, Yong Qiang; Zhang, Hong Xia; Xia, Jian Chuan

doi:10.18632/oncotarget.8476

Cited by 59 publications

(58 citation statements)

References 47 publications

(49 reference statements)

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“…Unexpectedly, in multivariate analysis, CTLA4 expression only correlated with patient survival in the unaltered peritumoral group. In patients with ESCC, increased CTLA4 levels have been implicated to be associated with shorter overall survival in multivariate analysis [30]. Hence, patients with increased CTLA4 expression in EACs might benefit from a CTLA4 blockade.…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory microenvironment of esophageal adenocarcinomas negatively impacts survival

Karstens

Kempski

Giannou

et al. 2020

Cancer Immunol Immunother

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Objective Reflux promotes esophageal adenocarcinomas (EACs) creating a chronic inflammatory environment. Survival rates are low due to early local recurrences and distant metastasis. Hence, there is a need for new potential treatment options like immunotherapies. However, the inflammatory microenvironment in EACs and its impact on patient outcome remain to be fully understood. Methods mRNA expression levels of pro-and anti-inflammatory markers in 39 EAC patients without neoadjuvant radiochemotherapy were measured. Data were confirmed using flow cytometric analysis of freshly resected surgical specimens. Inflammatory alterations in premalignant lesions of Barrett's esophagus were analyzed by immunohistochemistry. Results Expression levels of IL22 were reduced in EAC, while expression levels of FOXP3, IL10 and CTLA4 were increased. Flow cytometry demonstrated a strong infiltration of CD4 + T cells with a reduction in CD4 + T cells producing IL-22 or IL-17A. We also observed an increase in CD4 + CD127 low FOXP3 + cells producing IL-10. Accumulation of FOXP3 + T cells occurred prior to malignant changes. High expression of IL10 and low expression of IL22 in EAC were associated with reduced overall survival. Moreover, increased expression of IL10, CTLA4 and PD1 in the unaltered esophageal mucosa distant to the EAC was also linked with an unfavorable prognosis. Conclusion EAC shows an anti-inflammatory environment, which strongly affects patient survival. The microscopically unaltered peritumoral tissue shows a similar anti-inflammatory pattern indicating an immunological field effect, which might contribute to early local recurrences despite radical resection. These data suggest that using checkpoint inhibitors targeting anti-inflammatory T cells would be a promising therapeutic strategy in EAC.

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Section: Discussionmentioning

confidence: 99%

Anti-inflammatory microenvironment of esophageal adenocarcinomas negatively impacts survival

Karstens

Kempski

Giannou

et al. 2020

Cancer Immunol Immunother

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“…However, there are some reports supporting the notion that CTLA-4 is also expressed on non-T cells, such as solid tumors (11)(12)(13)(14). A recent study demonstrated that patients overexpressing CTLA-4 in esophageal cancer cells tend to have a poor prognosis (15).…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic T lymphocyte associated antigen 4 expression predicts poor prognosis in luminal B HER2-negative breast cancer

Lan

Wen

et al. 2018

Oncol Lett

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“…In addition to T cells, CTLA-4 is expressed on cell lines derived from a variety of human malignant solid tumour types, including melanoma, neuroblastoma, oesophageal carcinoma, lung cancer, gastric and colorectal cancer types (13,15,17,18). CTLA-4 was revealed to serve a function in the protection against apoptosis (18).…”

Section: Discussionmentioning

confidence: 99%

“…CTLA-4 has also been implicated to serve functions in neoplastic cells, including B cell chronic lymphocytic leukaemia (10), non-Hodgkin's lymphoma (11), breast cancer (12), lung cancer (13), melanoma (14), gastric cancer (15), colorectal cancer (15), cervical cancer (16) and oesophageal carcinoma (17). Prior studies indicated that CTLA-4 expression in tumour cells is associated with poor prognosis (12,17).…”

Section: Introductionmentioning

confidence: 99%

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Potential function of CTLA‑4 in the tumourigenic capacity of melanoma stem cells

Zhang

Dang

et al. 2018

Oncol Lett

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Abstract. Extensive clinical evidence supports that cytotoxic T lymphocyte antigen-4 (CTLA-4) is expressed in a variety of human malignant tumour cells in addition to T cells. In certain types of cancer, the overexpression of CTLA-4 is associated with poor patient prognosis. However, few studies have demonstrated the effects of tumour-intrinsic CTLA-4 in cancer stem cells, including melanoma stem cells (MSCs). In the present study, it was demonstrated that melanoma cell-intrinsic CTLA-4 induced tumour cell proliferation in vitro and suppressed tumour cell apoptosis. Furthermore, CTLA-4 was expressed in aldehyde dehydrogenase (ALDH) + MSCs. CTLA-4 inhibited MSCs proliferation in vitro by blocking antibodies and significantly downregulated ALDH1A1, ALDH1A3 and ALDH2 mRNA expression (P<0.01). Functionally, blocking CTLA-4 in melanoma cell lines suppressed the properties of stem-like cells, including ALDH activity and significantly suppressed the ability of these cells to form spheres in vitro (P<0.05). In addition, the blocking of CTLA-4 in melanoma cells suppressed the properties of stem-like cells in vivo, including the capacity for tumourigenesis. The presence of residual ALDH + MSCs within the tumour was observed, and the blocking CTLA-4 significantly decreased the number of residual ALDH + MSCs in vivo (P<0.01). Altogether, these results indicate the identification of a novel mechanism underlying melanoma progression in the present study and that CTLA-4-targeted therapy may benefit candidate CTLA-4-targeted therapy by improving the long-term outcome for patients with advanced stages of melanoma.

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Cytotoxic T lymphocyte antigen-4 expression in esophageal carcinoma: implications for prognosis

Cited by 59 publications

References 47 publications

Anti-inflammatory microenvironment of esophageal adenocarcinomas negatively impacts survival

Anti-inflammatory microenvironment of esophageal adenocarcinomas negatively impacts survival

Cytotoxic T lymphocyte associated antigen 4 expression predicts poor prognosis in luminal B HER2-negative breast cancer

Potential function of CTLA‑4 in the tumourigenic capacity of melanoma stem cells

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