Secreted Factors by Anaplastic Thyroid Cancer Cells Induce Tumor-Promoting M2-like Macrophage Polarization through a TIM3-dependent Mechanism

STEMPIN, CC; GEYSELS, RC; PARK, S; PALACIOS, LM; VOLPINI, X; MOTRAN, CC; ACOSTA RODRIGUEZ, EV; NICOLA, JP; CHENG, S; PELLIZAS, CG; FOZZATTI, L

Cancers

MDPI

Lugar: Basel; Año: 2021 vol. 13

2072-6694

naplastic thyroid cancer (ATC) is a highly aggressive type of thyroid cancer (TC). Currently, no effective target treatments are available that can improve overall survival, with ATC representing a major clinical challenge because of its remarkable lethality. Tumor-associated macrophages (TAMs) are the most evident cells in ATCs and their high density is correlated with a poor prognosis. However, the mechanisms of how TAMs promote ATC progression remain poorly characterized. Here, we demonstrated that the treatment of human monocytes (THP-1 cells) with ATC cell-derived conditioned media (CM) promoted macrophage polarization, showing high levels of M2 markers. Furthermore, we found that STAT3 was activated, and this was correlated with an increased expression and secretion of the inflammatory cytokine interleukin-6. Remarkably, the M2-like macrophages obtained revealed tumor-promoting activity. A cytokine array analysisdemonstrated that M2-like macrophage-derived CM contained high leve