Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA.
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI, USA.
Sci Rep. 2024 Oct 16;14(1):24230. doi: 10.1038/s41598-024-75265-9.
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.
肿瘤相关巨噬细胞（TAMs）被认为是肿瘤微环境（TME）中的一种细胞群体，它们可能在抑制前列腺 TME 中有效 T 细胞反应方面发挥着至关重要的作用。在本手稿中，我们利用一种新颖的微尺度细胞培养平台，即 Stacks，来研究由前列腺癌细胞系、原代巨噬细胞和来自前列腺癌患者的自体 T 细胞组成的单、共、三培养 TME 模型。通过对这些多细胞前列腺肿瘤模型进行多重分析，我们捕捉到了原代 TAMs 和活化 T 细胞之间的动态相互作用，导致相互作用时两个细胞群体的互惠性促炎激活。这些发现表明，活化的 T 细胞能够在前列腺肿瘤模型的背景下重新编程免疫抑制性 TAMs，并且 TAM 重编程可能在恢复前列腺 TME 中促炎 T 细胞肿瘤反应方面发挥关键的支持作用。
