(175u) Salinomycin Modulates Antitumor Immune Response By Repolarized Tumor-Associated Macrophages Toward M1 Phenotype

Huan Shen^{1, 2}, Junbo Gong ^1,2*

¹ National Engineering Research Center of Industry
Crystallization Technology, Tianjin University, Tianjin, China

² The Co-Innovation Center of Chemistry and Chemical Engineering
of Tianjin, Tianjin University, Tianjin, China
shenhuan@tju.edu.cn

Abstract: Tumor-associated macrophages (TAMs)
is an important component of tumor microenvironment. Repolarizing
tumor-associated macrophages (TAMs, which is dominated by the M2 forms) into
M1- phenotype has been recognized as a promising strategy to ameliorate the immunosuppressive microenvironment and improve both innate
and adaptive antitumor immunity. However, M2-orientated
differentiation of TAMs is hard to regulate and always leads to uncontrolled
inflammation which may otherwise promote tumor metastasis. Herein we showed
that salinomycin (SAL) operating as a selective agent
against CSCs can function as an antitumor immune modulator that switches TAMs
from M2 to tumor-killing M1 phenotype. In vitro results revealed that SAL significantly
upregulated M1-related IL1¦Á, iNOS and CCL2 in cocultured
assay (4T1 and RAW264.7), while decreased M2-related mRNA as CD206, IL10, Arg1
and Ym1(Fig1A, B and C). Furthermore, the survival of tumor bearing mouse
treated with intratumorally injected SAL was extended than either PBS, paclitaxel,
or LPS treated group, which could be attributed to the modulating effects of
SAL on TAMs (Fig1D, E and F). Our research provides a novel therapy
strategy by applying controlled repolarization of TAMs with SAL as an immunoactivator in cancer immunotherapy.

Fig1. A Sketch
depicting the coculture assay. B and C
The mRNA expression of M1 and M2 genes were detected by real-time PCR. D Tumor growth curve. E
The survival profile. F Percentage
of M¦µ in tumor tissue examined by flow cytometry.