期刊
JOURNAL FOR IMMUNOTHERAPY OF CANCER
卷 6, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s40425-018-0446-3
关键词
Dendritic cells; DC-LAMP; CD8(+) cytotoxic T lymphocytes; Natural killer cells; Tertiary lymphoid structures
资金
- BBMRI-CZ [LM2015089]
- European Regional Development Fund-Project BBMRI-CZ.: Biobank network-a versatile platform for research on the etiopathogenesis of diseases [EF16 013/0001674]
- Department of Radiation Oncology at Weill Cornell Medicine (New York, US)
- [PROGRES Q40/11]
- [PROGRES 28]
A high density of tumor-infiltrating CD8(+) T cells and CD20(+) B cells correlates with prolonged survival in patients with a wide variety of human cancers, including high-grade serous ovarian carcinoma (HGSC). However, the potential impact of mature dendritic cells (DCs) in shaping the immune contexture of HGSC, their role in the establishment of T cell-dependent antitumor immunity, and their potential prognostic value for HGSC patients remain unclear. We harnessed immunohistochemical tests and biomolecular analyses to demonstrate that a high density of tumor-infiltrating DC-LAMP(+) DCs is robustly associated with an immune contexture characterized by T(H)1 polarization and cytotoxic activity. We showed that both mature DCs and CD20(+) B cells play a critical role in the generation of a clinically-favorable cytotoxic immune response in HGSC microenvironment. In line with this notion, robust tumor infiltration by both DC-LAMP(+) DCs and CD20(+) B cells was associated with most favorable overall survival in two independent cohorts of chemotherapy-naive HGSC patients. Our findings suggest that the presence of mature, DC-LAMP(+) DCs in the tumor microenvironment may represent a novel, powerful prognostic biomarker for HGSC patients that reflects the activation of clinically-relevant anticancer immunity.
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