Nocardia rubra cell wall skeleton regulates tumour‐associated macrophage polarization by reprogramming M2 macrophages into M1 macrophages via STAT1/STAT6 pathways

Abstract Targeted therapy with tumour‐associated macrophages (TAMs) has emerged as a new paradigm for immunotherapy of cervical cancer. Nocardia rubra cell wall skeleton (Nr‐CWS) for external use is an immunotherapeutic agent. In this study, we aimed to explore the effects of Nr‐CWS on TAMs and the potential mechanisms. Cervical tissue samples were collected before and after Nr‐CWS treatment from patients with high‐risk HPV infection and cervical intraepithelial neoplasia (CIN). The effect of Nr‐CWS on macrophages in vivo was examined by immunohistochemistry and double‐labeling immunofluorescence histochemistry. In vitro experiments were performed using a TAM model established by THP‐1 cells under Nr‐CWS treatment. We found that Nr‐CWS treatment significantly reduced the numbers of total macrophages and M2 macrophages, increased the proportion of M1 macrophages and decreased the proportion of M2 macrophages in cervical tissues. After Nr‐CWS treatment in vitro, the expression levels of the M1 macrophage markers were increased, while the expression levels of the M2 macrophage markers were decreased. Nr‐CWS treatment also activated STAT1 pathways but inhibited STAT6 pathways. These results indicated that Nr‐CWS may improve local immune response and reverse immunosuppression by regulating the M2 to M1 polarization of TAMs via STAT1/STAT6 pathways.