Normal and Oropharyngeal-carcinoma derived monocyte responses to OPC-cell line conditioned media.
Tumor Associated Macrophages (TAMs) represent a critical immunological barrier to effective anti-tumor mechanisms of developing carcinomas of the oropharynx. Tumor infiltrating monocytes become activated and differentiate into TAMs which contribute to the immunological landscape of tumors as either containing or devoid of effector T-cells. We first compared transcriptional responses of normal and OPC derived monocytes from single individuals, at the single cell level, after exposure to media conditioned by SCC-25 and SCC-154 OPC cell lines. Since media conditioned by both SCC-154 and SCC-25 contain secreted IL1a, stimulation of these monocytes with recombinant IL1a was included as a control. We showed that to these conditioned media, CXCL1, CXCL5 and CCL2 transcripts reached higher levels in a greater proportion of OPC-patient monocytes compared to control monocytes. These early monocyte responses were validated in a cohort of isolated monocytes exposed to the same media. These findings represent that monocytes may be secreting TME influencing cytokines, prior to their own differentiation, which in turn recruit detrimental cell populations including T-regs, MDSCs and other monocytes. Overall design: Primary monocytes from a healthy and OPC-diagnosed individual were stimulated with culture media conditioned by SCC-25 or SCC-154 OPC cell lines, or recombinant human IL-1a.