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
{"title":"Modulation of Human Immune Cells by Propyl-Propane Thiosulfonate (PTSO) Inhibits Colorectal Tumor Progression in a Humanized Mouse Model.","authors":"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","doi":"10.3390/nu17182993","DOIUrl":null,"url":null,"abstract":"<p><p><b>Background/Objectives</b>: 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 <i>Allium</i> 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. <b>Methods</b>: Human peripheral blood mononuclear cells (hPBMCs) were incubated with PTSO (25 μM for 48 h) and characterized by flow cytometry. These cells (1 × 10<sup>6</sup>) 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). <b>Results</b>: PTSO reduced MDSC populations, specifically, it significantly reduced monocytic (M-MDSCs, Control: 7.27 ± 0.53% vs. PTSO: 4.70 ± 2.39%; <i>p</i> = 0.0458) and polymorphonuclear (PMN-MDSCs, Control: 5.28 ± 0.99% vs. PTSO: 3.41 ± 1.58%; <i>p</i> = 0.0385) MDSCs. In parallel, PTSO increased T cell subpopulations, particularly interferon gamma (IFNG)-producing cytotoxic CD8<sup>+</sup> T cells (Control: 9.52 ± 2.06% vs. PTSO: 15.04 ± 5.01%; <i>p</i> = 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 cm<sup>3</sup> vs. PTSO: 0.44 ± 0.35 cm<sup>3</sup>; <i>p</i> = 0.0068), accompanied by increased infiltration of CD4<sup>+</sup> T lymphocytes and Natural Killer (NK) cells and downregulation of immunosuppressive genes. These effects resulted in a reduction in cancer cell proliferation and invasiveness. <b>Conclusions</b>: 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.</p>","PeriodicalId":19486,"journal":{"name":"Nutrients","volume":"17 18","pages":""},"PeriodicalIF":5.0000,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472244/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nutrients","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3390/nu17182993","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}
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.
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.