Modulation of Human Immune Cells by Propyl-Propane Thiosulfonate (PTSO) Inhibits Colorectal Tumor Progression in a Humanized Mouse Model.

IF 5 2区 医学 Q1 NUTRITION & DIETETICS
Nutrients Pub Date : 2025-09-18 DOI:10.3390/nu17182993
María Jesús Rodríguez-Sojo, Luckman Gbati, Jose Alberto Molina-Tijeras, Ailec Ho-Plágaro, Teresa Vezza, Laura López-Escánez, Carmen Griñán-Lisón, Juan Antonio Marchal, Alberto Baños, María José Rodríguez-Sánchez, Jorge García-García, Antonio Jesús Ruiz-Malagón, Julio Gálvez, María Elena Rodríguez-Cabezas, Alba Rodríguez-Nogales
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引用次数: 0

Abstract

Background/Objectives: Colorectal cancer (CRC) remains a major global health challenge and current therapies are not always effective. In addition, certain immune cell populations, such as myeloid-derived suppressor cells (MDSCs), pose a significant barrier to immune-based treatments. Some phytochemicals, particularly compounds derived from Allium spp. like Propyl-Propane Thiosulfonate (PTSO), have shown strong immunomodulatory potential in digestive disorders. This study aims to investigate the capacity of PTSO to modulate immune responses and affect tumor progression in CRC models, in vitro and in vivo, with a focus on the immune cell populations that comprise the tumor microenvironment. Methods: Human peripheral blood mononuclear cells (hPBMCs) were incubated with PTSO (25 μM for 48 h) and characterized by flow cytometry. These cells (1 × 106) were then injected into NOD scid gamma (NSG) immunodeficient mice, which were simultaneously induced to develop a subcutaneous tumor by injection of HCT116 enriched cancer stem cells (CSCs) colonospheres (60,000 cells/mouse). Results: PTSO reduced MDSC populations, specifically, it significantly reduced monocytic (M-MDSCs, Control: 7.27 ± 0.53% vs. PTSO: 4.70 ± 2.39%; p = 0.0458) and polymorphonuclear (PMN-MDSCs, Control: 5.28 ± 0.99% vs. PTSO: 3.41 ± 1.58%; p = 0.0385) MDSCs. In parallel, PTSO increased T cell subpopulations, particularly interferon gamma (IFNG)-producing cytotoxic CD8+ T cells (Control: 9.52 ± 2.06% vs. PTSO: 15.04 ± 5.01%; p = 0.0685). In the humanized tumor xenograft mouse, the administration of PTSO-pretreated hPBMCs led to a significant reduction in tumor size (Control: 1.43 ± 0.82 cm3 vs. PTSO: 0.44 ± 0.35 cm3; p = 0.0068), accompanied by increased infiltration of CD4+ T lymphocytes and Natural Killer (NK) cells and downregulation of immunosuppressive genes. These effects resulted in a reduction in cancer cell proliferation and invasiveness. Conclusions: The dual effect of PTSO on immune cell populations, reducing immunosuppressive myeloid cells and enhancing effector T lymphocyte and NK cell responses, resulted in an anti-tumor effect, highlighting this bioactive compound as a promising adjuvant in CRC immunotherapy and opening avenues for future research combining immunotherapy with PTSO in alternative models to optimize dosing and enhance translational potential.

丙基丙烷硫代磺酸盐(PTSO)调节人类免疫细胞抑制人源化小鼠模型结肠直肠癌进展
背景/目的:结直肠癌(CRC)仍然是一个主要的全球健康挑战,目前的治疗方法并不总是有效的。此外,某些免疫细胞群,如髓源性抑制细胞(MDSCs),对基于免疫的治疗构成重大障碍。一些植物化学物质,特别是从葱属植物中提取的化合物,如丙基丙烷硫代磺酸盐(PTSO),在消化系统疾病中显示出强大的免疫调节潜力。本研究旨在研究PTSO在体外和体内调节CRC模型中免疫反应和影响肿瘤进展的能力,重点关注构成肿瘤微环境的免疫细胞群。方法:人外周血单个核细胞(hPBMCs)用25 μM的PTSO培养48 h,流式细胞术检测。然后将这些细胞(1 × 106)注射到NOD scid γ (NSG)免疫缺陷小鼠体内,同时通过注射富含HCT116的癌症干细胞(CSCs)结肠球(60,000个细胞/小鼠)诱导其形成皮下肿瘤。结果:PTSO减少了MDSC的数量,其中单核细胞(M-MDSCs,对照组:7.27±0.53%,PTSO: 4.70±2.39%,p = 0.0458)和多形核细胞(PMN-MDSCs,对照组:5.28±0.99%,PTSO: 3.41±1.58%,p = 0.0385)的MDSCs数量显著减少。与此同时,PTSO增加T细胞亚群,特别是产生干扰素γ (IFNG)的细胞毒性CD8+ T细胞(对照组:9.52±2.06% vs. PTSO: 15.04±5.01%;p = 0.0685)。在人源化的肿瘤移植小鼠中,PTSO预处理的hPBMCs导致肿瘤大小显著减小(对照组:1.43±0.82 cm3 vs. PTSO: 0.44±0.35 cm3; p = 0.0068),并伴有CD4+ T淋巴细胞和自然杀伤细胞(NK)的浸润增加和免疫抑制基因的下调。这些作用导致癌细胞增殖和侵袭性的减少。结论:PTSO对免疫细胞群的双重作用,减少免疫抑制的骨髓细胞,增强效应T淋巴细胞和NK细胞的反应,导致抗肿瘤作用,突出了这种生物活性化合物作为CRC免疫治疗的一种有前景的佐剂,并为未来在替代模型中将免疫治疗与PTSO联合研究开辟了道路,以优化剂量和增强转化潜力。
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
Nutrients
Nutrients NUTRITION & DIETETICS-
CiteScore
9.20
自引率
15.30%
发文量
4599
审稿时长
16.74 days
期刊介绍: Nutrients (ISSN 2072-6643) is an international, peer-reviewed open access advanced forum for studies related to Human Nutrition. It publishes reviews, regular research papers and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.
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