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活化的 T 细胞与肿瘤相关巨噬细胞之间的动态相互作用驱动了前列腺肿瘤模型中巨噬细胞的重编程和促炎 T 细胞的迁移。

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

机构信息

Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA.

Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI, USA.

出版信息

Sci Rep. 2024 Oct 16;14(1):24230. doi: 10.1038/s41598-024-75265-9.

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b105/11484957/b7fe4269f3a3/41598_2024_75265_Fig1_HTML.jpg

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