IL-10 is overexpressed in human cutaneous T-cell lymphoma and is required for maximal tumor growth in a mouse model

Abstract

A crucial question pertains to a role of IL-10 as a tumorigenic factor, or just a marker of advanced disease in cutaneous T-cell lymphoma (CTCL). Herein, we measured significantly elevated IL-10 mRNA in a cohort of skin samples of patients with CTCL. Increased IL-10 was also detected in the tumor microenvironment of an established inflammation-dependent murine model of using MBL2 T lymphoma cells. Conditioned media from MBL2 cells was able to stimulate IL-10 production in bone marrow-derived macrophages in an IL-4-dependent manner. Implanted MBL2 T-cell lymphomas in IL-10KO mice were 50% smaller, accompanied by decreased numbers of infiltrating macrophages and reduced efficiency of M2-polarization compared with wild-type mice. With anti-IL-10R mAb treatment, both wild-type tumor-bearing mice and IL-10KO mice exhibited a further growth inhibition. Our data indicate that targeting IL-10 signaling with neutralizing antibodies to IL-10 or its receptor may have a great potential for advanced CTCL therapy.

Keywords:

• IL-10 (interleukin-10)
• CTCL (cutaneous T-cell lymphoma)
• macrophages
• tumor immunology

Acknowledgments

The authors thank the UC Davis Pathology Biorepository for carrying out histology sectioning and staining procedures. The authors also thank their colleague, Dr. Maxwell A. Fung, UC Davis School of Medicine, for consultation and evaluation of tumor tissues by microscopy. The authors thank UC Davis colleagues Dr. Yan Zhou, Dr. Sebastian Yu, and Dr. Dan Han for technical support.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at http://dx.doi.org/10.1080/10428194.2018.1516037.