Infiltration of T cells promotes the metastasis of ovarian cancer cells via the modulation of metastasis-related genes a
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ORIGINAL ARTICLE
Infiltration of T cells promotes the metastasis of ovarian cancer cells via the modulation of metastasis‑related genes and PD‑L1 expression Jing‑Jing Wang1 · Michelle Kwan‑Yee Siu1 · Yu‑Xin Jiang1 · David Wai Chan1 · Annie Nga‑Yin Cheung2 · Hextan Yuen‑Sheung Ngan1 · Karen Kar‑Loen Chan1 Received: 4 April 2020 / Accepted: 21 May 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Due to its high ability to disseminate, ovarian cancer remains one of the largest threats to women’s health, worldwide. Evidence showed that the immune cells infiltrating the tumor microenvironment are crucial in mediating metastasis. Therefore, it is necessary to understand which types of immune cells are involved in metastasis, and to determine the mechanisms by which they influence the process. By immunohistochemistry, we found that higher concentrations of intratumoral C D8+ T cells were found to be correlated with an advanced grade and stage of ovarian cancer. Additionally, the infiltration of stromal CD8+ T cells was also significantly higher in tissues with advanced stages and metastatic tumors. A positive correlation between the infiltration of F oxP3+ Treg cells and histological grade was also observed, regardless of location. PD-L1 expression in metastatic tumors was also higher than that in paired primary ovarian tumors. Transwell migration and invasion assays revealed the increased migration and invasion of ovarian cancer cell lines (A2780CP and ES2) and ascites-derived ovarian cancer cells following co-culturing with C D8+ T cells. Enhanced expression of MMP-9, uPA, VEGF, bFGF, IL-8, IL-10, and PD-L1 by cancer cells following co-culturing with C D8+ T cells were also detected by qPCR, ELISA or flow cytometry. In conclusion, our findings suggest that the infiltrated T cells could promote the development of ovarian cancer, and provide another mechanism of immune evasion mediated by T cells. Keywords T cells · Metastasis · PD-L1 · Ovarian cancer
Introduction As one of the most common female malignancies worldwide, ovarian cancer accounts for more deaths annually than other gynecologic cancers[1]. Because of the insidious symptoms in the early stage of disease, the majority of patients present with an advanced stage of ovarian cancer that has disseminated beyond the ovaries and pelvic organs. Additionally, the high mortality rate of ovarian cancer is Jing-Jing Wang and Michelle Kwan-Yee Siu have contributed equally to this work. * Karen Kar‑Loen Chan [email protected] 1
Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, Special Administrative Region of China
Department of Pathology, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, Special A dministrative Region of China
2
due its high metastasis rate. Approximately, 41% of patients with stage III and 20% of patients with stage IV epithelial ovarian cancer reach five-year survivals. In contrast, however, more than 70% of patien
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