Extracellular vesicles related gene HSPH1 exerts anti-tumor effects in prostate cancer via promoting the stress response of CD8 + T cells

IF 6.6 2区医学 Q1 Medicine

Cellular Oncology Pub Date : 2024-01-02 DOI:10.1007/s13402-023-00905-7

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引用次数: 0

Abstract

Background

T cell stress response state (TSTR), as a novel immune concept previous studies have proposed, has not yet been explored in prostate cancer (PC). As a type of cellular efflux, exosomes play important roles in the occurrence and development of PC.

Method

Here, we conducted a combined analysis on extracellular vesicle related genes (EVRGs) in PC using data from single-cell RNA (scRNA), spatial transcriptome (ST), and bulk RNA sequencing.

Result

Preliminary findings have revealed that heat shock protein family H (Hsp110) member 1 (HSPH1) possesses two identities, one being EVRGs and the other being a member of the heat shock protein family involved in TSTR, which may promote the differentiation of conventional T cells towards Th1 or Th2 cells through the pathway of IL2-MYC-IL2RA, thereby promoting the increase of CD8 + T cells in the tumor area, especially in the invasive zone, and inhibiting the invasion of PCs. We also notice the negative response of HSPH1 + CD8 + T cell related genes in immune checkpoint blockade (ICB). Western blot (WB) and droplet digital Polymerase Chain Reaction (ddPCR) demonstrated that the mRNA and protein levels of HSPH1 in EVs of PCs were significantly higher than those in adjacent tissues.

Conclusion

Results above indicate the potential of HSPH1 as a critical therapeutic target in PC.

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细胞外囊泡相关基因 HSPH1 通过促进 CD8 + T 细胞的应激反应对前列腺癌发挥抗肿瘤作用

摘要背景 T细胞应激反应状态（TSTR）是以往研究提出的一种新的免疫概念，但尚未在前列腺癌（PC）中得到探讨。外泌体作为一种细胞外流体，在前列腺癌的发生和发展中发挥着重要作用。方法我们利用单细胞 RNA（scRNA）、空间转录组（ST）和大容量 RNA 测序数据，对 PC 中的细胞外囊泡相关基因（EVRGs）进行了综合分析。结果初步研究结果表明，热休克蛋白家族 H（Hsp110）成员 1（HSPH1）具有两种身份，一种是 EVRGs，另一种是参与 TSTR 的热休克蛋白家族成员，可能通过 IL2-MYC-IL2RA 途径促进传统 T 细胞向 Th1 或 Th2 细胞分化，从而促进肿瘤区域尤其是侵袭区 CD8 + T 细胞的增加，抑制 PCs 的侵袭。我们还注意到 HSPH1 + CD8 + T 细胞相关基因在免疫检查点阻断（ICB）中的负反应。Western blot（WB）和液滴数字聚合酶链反应（ddPCR）表明，PCs EVs 中 HSPH1 的 mRNA 和蛋白水平明显高于邻近组织。结论上述结果表明，HSPH1 有可能成为 PC 的关键治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cellular Oncology Biochemistry, Genetics and Molecular Biology-Cancer Research

CiteScore

10.40

自引率

1.50%

发文量

审稿时长

16 weeks

期刊介绍： The Official Journal of the International Society for Cellular Oncology Focuses on translational research Addresses the conversion of cell biology to clinical applications Cellular Oncology publishes scientific contributions from various biomedical and clinical disciplines involved in basic and translational cancer research on the cell and tissue level, technical and bioinformatics developments in this area, and clinical applications. This includes a variety of fields like genome technology, micro-arrays and other high-throughput techniques, genomic instability, SNP, DNA methylation, signaling pathways, DNA organization, (sub)microscopic imaging, proteomics, bioinformatics, functional effects of genomics, drug design and development, molecular diagnostics and targeted cancer therapies, genotype-phenotype interactions. A major goal is to translate the latest developments in these fields from the research laboratory into routine patient management. To this end Cellular Oncology forms a platform of scientific information exchange between molecular biologists and geneticists, technical developers, pathologists, (medical) oncologists and other clinicians involved in the management of cancer patients. In vitro studies are preferentially supported by validations in tumor tissue with clinicopathological associations.