Targeting STAT3 phosphorylation by neem leaf glycoprotein prevents immune evasion exerted by supraglottic laryngeal tumor induced M2 macrophages

Tumor-associated macrophages (TAMs) are preferentially M2 skewed and promote tumor growth, angiogenesis, invasion, and/or metastasis. In this study, we have analyzed the in vitro immunomodulatory potential of a non-toxic neem leaf glycoprotein (NLGP) in reprogramming Stage III supraglottic laryngeal tumor cell lysate (SLTCL) induced M2 TAMs to their classical anti-tumor shape (M1). Data generated from this study support that NLGP is effective in preventing the SLTCL induced generation (CD68+CD206+IL-10high to CD68+CD206−IL-10low TAMs) and functions (NOlow to NOhigh, MHC-Ilow to MHC-Ihigh, CD80low to CD80high) of pro-tumorous M2 macrophages, which in turn associated with sustained anti-tumor effector functions by promoting cytotoxic T cell activities and suppressing regulatory T cells. Furthermore, our data also suggest that NLGP prevents M2 skewness of TAMs by downregulating phosphorylation of targeted STAT3.