Senescent Thyrocytes, Similarly to Thyroid Tumor Cells, Elicit M2-like Macrophage Polarization In Vivo.

Abstract

Simple SummarySeveral studies including ours suggest a pro-tumoral role of senescent thyrocytes in thyroid tumors. On the other hand, M2-like tumor associated macrophages infiltration increases with thyroid cancer aggressiveness. In this work, we used senescent thyrocytes and thyroid tumor cells as models of early and late tumor stages, respectively, and demonstrated their in vivo capability to recruit and polarize macrophages toward a pro-tumoral M2-like phenotype. These findings pave the way for the design of new therapeutic approaches for thyroid tumors based on the elimination or activity modulation of senescent cells and/or infiltrating macrophages.Inflammation plays a critical role in thyroid cancer onset and progression. We previously characterized the in vitro interplay between macrophages and senescent human thyrocytes and thyroid tumor-derived cell lines, modeling the early and the late thyroid tumor phases, respectively. We reported that both models are able to induce pro-tumoral M2-like macrophage polarization, through the activation of the COX2-PGE2 axis. Here, we investigated the presence of macrophage infiltrating cells in mouse xenografts derived from the above described cells models. We showed that subcutaneous injection in immunodeficient mice of both senescent human thyrocytes and thyroid tumor-derived cell lines elicits macrophage recruitment. Furthermore, considering the type of macrophage infiltrate, we observed a stronger infiltration of Arginase I positive cells (M2-like). Overall, these results demonstrate the in vivo capability of senescent and tumor thyroid cells to recruit and polarize macrophages, suggesting that the promotion of a pro-tumoral microenvironment through tumor associated macrophages may occurs in late as well as in early thyroid tumor stages, favoring tumor onset and progression.