Cryo-thermal therapy induces macrophage polarization for durable anti-tumor immunity.

Abstract

Many cancer therapies are being developed for the induction of durable anti-tumor immunity, especially for malignant tumors. The activation of antigen-presenting cells (APCs), including macrophages and dendritic cells (DCs), can bridge innate and adaptive immune responses against tumors. However, APCs have an immunosuppressive phenotype and reversing it for effective tumor-specific antigen presenting is critical in developing new cancer treatment strategies. We previously developed a novel cryo-thermal therapy to treat malignant melanoma in a mouse model; long-term survival and durable anti-tumor immunity were achieved, but the mechanism involved was unclear. This study revealed cryo-thermal therapy-induced macrophage polarization to the M1 phenotype and modulated the phenotypic and functional maturation of DCs with high expression of co-stimulatory molecules, increased pro-inflammatory cytokine production, and downregulated immuno-inhibitory molecule expression. Further, we observed CD4+ T-cell differentiation into Th1 and cytotoxic T-cell sub-lineages and generation of cytotoxic CD8+ T cells, in which M1 macrophage polarization had a direct, important role. The results indicated that cryo-thermal-induced macrophage polarization to the M1 phenotype was essential to mediate durable anti-tumor immunity, leading to long-term survival. Thus, cryo-thermal therapy is a promising strategy to reshape host immunosuppression, trigger persistent memory immunity for tumor eradication, and inhibit metastasis in the long term.

• Authors: Kun He, Shengguo Jia, Yue Lou, Ping Liu, Lisa X Xu
• Journal: Cell death & disease (Cell Death Dis) Vol. 10 Issue 3 Pg. 216 (03 04 2019) ISSN: 2041-4889 [Electronic] England
• PMID: 30833570 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Animals
• Antigen-Presenting Cells (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• Cell Differentiation
• Cryotherapy
• Female
• Immunotherapy (methods)
• Lung Neoplasms (immunology, prevention & control, secondary)
• Melanoma, Experimental (immunology, pathology)
• Mice
• Mice, Inbred C57BL
• Neoplasm Metastasis (immunology, prevention & control)
• Neoplasms (immunology)