肿瘤源性 Hsp70-CD14 相互作用通过激活肿瘤相关巨噬细胞表达 CC 趋化因子和 CD40 共刺激分子,增强细胞毒性 T 细胞的抗肿瘤潜力。
Tumor-derived Hsp70-CD14 interaction enhances the antitumor potential of cytotoxic T cells by activating tumor-associated macrophages to express CC chemokines and CD40 costimulatory molecules.
发表日期:2024 Jun 28
作者:
Sanjay Kumar, Vijay Mohan, Rishi Kant Singh, Pramod Kumar Gautam, Sandeep Kumar, Alok Shukla, Anand Kumar Patel, Lokesh Yadav, Arbind Acharya
来源:
INTERNATIONAL IMMUNOPHARMACOLOGY
摘要:
热休克蛋白是一类分布广泛的蛋白质。它在几乎所有生物体中组成型表达,并且在整个进化过程中几乎没有变化。此前,HSP,特别是 Hsp70,被认为是分子伴侣,有助于细胞中新合成的多肽进行正确的三维折叠。最近,研究人员重点关注免疫细胞的潜在诱导,包括巨噬细胞、抗原特异性 CD8 细胞毒性 T 细胞和 PBMC。它诱导 CC 趋化因子(如 MIP-1α 和 RANTES)的表达,这些趋化因子负责感染部位免疫细胞的趋化运动和迁移,以中和体内和体外多种细胞系中的外来颗粒,但它们对肿瘤的影响相关的巨噬细胞仍然未知。已知这些细胞因子还会影响多种免疫细胞(包括 CD8 细胞毒性 T 细胞)向炎症部位的移动。因此,研究了肿瘤来源的自体Hsp70对肿瘤相关巨噬细胞(TAM)中MIP-1α和RANTES表达的影响。我们的结果表明,TAM 中 Hsp70 处理诱导的 MIP-1α 和 RANTES 表达显着高于 NMO 中。根据文献,CC趋化因子与HIV具有相同的受体CCR5,因此可以更好地完成病毒的配体结合。此外,Hsp70 预激活的 TAM 在共培养 48 小时期间诱导 T 细胞中 IL-2 和 IFN-γ 表达增加,并上调宿主的抗肿瘤免疫反应。因此,我们的研究结果可能有助于开发更好的方法来限制肿瘤的生长和进展。版权所有 © 2024。由 Elsevier B.V. 出版。
Heat shock proteins are a widely distributed group of proteins. It is constitutively expressed in almost all organisms and shows little variation throughout evolution. Previously, HSPs, particularly Hsp70, were recognized as molecular chaperones that aid in the proper three-dimensional folding of newly synthesized polypeptides in cells. Recently, researchers have focused on the potential induction of immune cells, including macrophages, antigen-specific CD8+ cytotoxic T cells, and PBMCs. It induces the expression of CC chemokines such as MIP-1α and RANTES, which are responsible for the chemotactic movement and migration of immune cells at the site of infection to neutralize foreign particles in vivo and in vitro in several cell lines but their effect on tumor-associated macrophages is still not known. These cytokines are also known to influence the movement of several immune cells, including CD8+ cytotoxic T cells, toward inflammatory sites. Therefore, the effect of tumor-derived autologous Hsp70 on the expression of MIP-lα and RANTES in tumor-associated macrophages (TAMs) was investigated. Our results indicated that Hsp70 treatment-induced MIP-lα and RANTES expression was significantly greater in TAMs than in NMOs. According to the literature, the CC chemokine shares the same receptor, CCR5, as HIV does for their action, and therefore could provide better completion to the virus for ligand binding. Furthermore, Hsp70-preactivated TAMs induced increased IL-2 and IFN-γ expression in T cells during coculture for 48 h and upregulated the antitumor immune response of the host. Therefore, the outcome of our study could be useful for developing a better approach to restricting the growth and progression of tumors.Copyright © 2024. Published by Elsevier B.V.