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Growth differentiation factor-15 promotes immune escape of ovarian cancer via targeting CD44 in dendritic cells.
- Source :
-
Experimental Cell Research . May2021, Vol. 402 Issue 1, pN.PAG-N.PAG. 1p. - Publication Year :
- 2021
-
Abstract
- Immune escape is the main cause of the low response rate to immunotherapy for cancer, including ovarian cancer. Growth differentiation factor-15 (GDF-15) inhibits immune cell function. However, only few reports described the mechanism. Therefore, the aim of this study was to investigate the mechanism of immune escape regulated by GDF-15 in ovarian cancer. Ovarian cancer patients and healthy women were enrolled in this study. Immunohistochemistry and ELISA were performed to measure GDF-15 expression. Immunoprecipitation combined with mass spectrometry, surface plasmon resonance, and co-immunoprecipitation assay were used to evaluate the interaction between GDF-15 and the surface molecules of DCs. Immunofluorescence analysis, flow cytometry and transwell assay were used to evaluate additional effects of GDF-15 on DCs. The results showed that GDF-15 expression was higher in the ovarian cancer patients compared to that in the healthy women. The TIMER algorithm revealed that highly GDF-15 expression is associated with immune DC infiltration in immunoreactive high-grade serous carcinoma. A further study showed that GDF-15 suppressed DCs maturation, as well as IL-12p40 and TNF-α secretion, the length and number of protrusions and the migration. More importantly, CD44 in the surface of DCs interacted with GDF-15. The overexpression of CD44 in DCs resulted in the suppression of the inhibitory effect of GDF-15 on the length and number of DC synapses. In DCs overexpressing CD44 the inhibition of GDF-15 on the expression of CD11c, CD83 and CD86 was decreased, while in DCs with a knockdown of CD44 the inhibition was further enhanced. Knockdown of CD44 in DCs enhanced the inhibitory effect of GDF-15 on DC migration, while the overexpression of CD44 inhibited the inhibitory effect of GDF-15 on DC migration. In conclusion, the present study suggested that GDF-15 might facilitate ovarian cancer immune escape by interacting with CD44 in DCs to inhibit their function. [Display omitted] [ABSTRACT FROM AUTHOR]
- Subjects :
- *OVARIAN cancer
*SURFACE plasmon resonance
*CELL physiology
*MASS spectrometry
Subjects
Details
- Language :
- English
- ISSN :
- 00144827
- Volume :
- 402
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Experimental Cell Research
- Publication Type :
- Academic Journal
- Accession number :
- 149633065
- Full Text :
- https://doi.org/10.1016/j.yexcr.2021.112522