Dynamic reciprocal interactions between activated T cells and tumor associated macrophages drive macrophage reprogramming and proinflammatory T cell migration within prostate tumor models

活化 T 细胞与肿瘤相关巨噬细胞之间的动态相互作用驱动前列腺肿瘤模型中的巨噬细胞重编程和促炎 T 细胞迁移

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作者:Erika Heninger, Matthew Thomas Breneman, Emma Elizabeth Recchia, Sheena Catherine Kerr, Reyna Elvan Dogru, Marina Nasrin Sharifi, Aaron Matthew LeBeau, David Kosoff

Abstract

Tumor-associated macrophages (TAMs) have been implicated as a tumor microenvironment (TME) cell population, which may be playing a vital role in the inhibition of effective T cell responses in the prostate TME. In this manuscript, we leverage a novel microscale cell culture platform, known as Stacks, to investigate mono-, co-, and tri-culture TME models comprised of prostate tumor cell lines, primary macrophages, and autologous T cells from patients with prostate cancer. Through multiplexed analysis of these multi-cellular prostate tumor models, we capture a dynamic interaction between primary TAMs and activated T cells that resulted in reciprocal proinflammatory activation of both cell populations upon interaction. These findings suggest that activated T cells are capable of reprogramming immunosuppressive TAMs in the context of prostate tumor models and that TAM reprogramming may play a key supportive role in restoring proinflammatory T cell tumor responses in the prostate TME.

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