Supraglottic laryngeal tumor microenvironmental factors facilitate STAT3 dependent pro-tumorigenic switch in tumor associated macrophages to render utmost immune evasion

Abstract

Content of tumor microenvironment (TME) is varied greatly among different types of laryngeal tumors, namely, supraglottic, glottic and subglottic tumors. These three different TMEs shape infiltrating monocytes/macrophages toward M2 genotypes in variable degrees. Results obtained from in vitro studies demonstrated extent of expression of M2 phenotypic features on macrophages was maximum after their exposure to supraglottic laryngeal tumor cell lysates (SLTCL) than glottic or subglottic lysates. Moreover, M2 macrophages generated under influence of SLTCL show less nitric oxide production, greater IL-10: IL-12 ratio and poor antigen presentation. Co-culture of such M2 macrophages with T cells from healthy donors resulted decreased activation of T cells and T cell mediated tumor cell cytotoxicity, than, glottic or subglottic. SLTCL mediated macrophage polarization is STAT3 dependent and might be one of the major factors for severe immune paralysis leading to poor prognosis of supraglottic laryngeal tumor bearer following standard treatment.