In March 2020, Professor Gao Xiao-ming's research group published a research paper entitled "Lactoferrin-containing immunocomplex mediates antitumor effects by resetting tumor-associated macrophages to M1 phenotype" in Journal for Immunotherapy of Cancer.
Tumor-associated macrophages (TAMs) resemble M2-polarized cells with potent immunosuppressive activity and play a pivotal role in tumor growth and progression. Converting TAMs to pro-inflammatory M1-like phenotype is thus an attractive strategy for activating anti-tumor immunity, which has been proved in both preclinical models and early clinical trials. In this study, we illustrated that LTF-IC could also induce such polarization switch in TAMs, as evidenced by increased TNF-α production, down-regulated M2-specific markers (CD206, ARG-Ⅰ and VEGF) and up-regulated M1-specific markers (CD86 and HLA-DR). More importantly, LTF-IC-treated TAMs acquired potent tumoricidal activity in vitro, and LTF-IC administration conferred superior anti-tumor efficacy and prolonged animal survival in vivo. In addition, LTF-IC-treated mice showed significantly less infiltration of immunosuppressive myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs). Collectively, our study demonstrated that LTF-IC could be used to target M2-like TAMs as a promising cancer therapeutic agent.
Dong Hongliang is the first author of this paper and Gao Xiaoming is the co-responding author. Yang Yueyao, Gao Chenhui, Sun Hehe et al. participated in the research. This work was supported by grants from the Ministry of Science and Technology (2017YFA0104502), and the Natural Science Foundation of China (31770942/31070738).
https://jitc.bmj.com/content/8/1/e000339