Effective suppression of tumor growth and hepatic metastasis of neuroblastoma by NKT-stimulatory phenyl glycolipid.

Biomed Pharmacother

Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Chang Gung University, Taoyuan, Taiwan; Department of Pediatrics, University of California in San Diego, La Jolla, CA, USA.

Published: August 2024

AI Article Synopsis

  • Invariant natural killer T (iNKT) cells can produce special proteins called cytokines when they are stimulated by a substance called α-GalCer.
  • A new version of this substance, called C34, has been found to work even better against certain cancers in mice, like breast cancer and melanoma.
  • C34 helps the immune system fight neuroblastoma (a type of cancer) by boosting the number of important immune cells in the liver and reducing bad cells that help tumors grow, leading to longer survival for the mice.

Article Abstract

Invariant natural killer T cell (iNKT) cells produce large amounts of cytokines in response to α-Galactosylceramide (α-GalCer) stimulation. An analog containing two phenyl rings on the acyl chain, C34, was previously found to be more Th1-biased than α-GalCer and triggered greater anticancer activities against breast cancer, melanoma and lung cancer in mice. Since liver is enriched in iNKT cells, we investigated anticancer efficacy of C34 on neuroblastoma with hepatic metastasis. C34 induced Th1-biased cytokine secretions in the liver, significantly suppressed neuroblastoma growth/metastasis and prolonged mouse survival. The anti-tumor efficacy might be attributed to greater expansions of hepatic NKT, NK, CD4 T, and CD8 T cells as well as reduction of the number of SSCGr1CD11b subset of myeloid-derived suppressor cells (MDSCs) in the liver of tumor-bearing mice, as compared to DMSO control group. C34 also upregulated expression of CD1d and CD11c, especially in the SSCGr1CD11b subset of MDSCs, which might be killed by C34-activated NKT cells, attributing to their reduced number. In addition, C34 also induced expansion of CD4 T, CD8 T, and NK cells, which might eliminate neuroblastoma cells. These immune-modulating effects of C34 might act in concert in the local milieu of liver to suppress the tumor growth. Further analysis of database of neuroblastoma revealed that patients with high CD11c expression in the monocytic MDSCs in the tumor had longer survival, suggesting the potential clinical application of C34 for treatment of neuroblastoma.

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Source
http://dx.doi.org/10.1016/j.biopha.2024.117040DOI Listing

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