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

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 × 10(6)) 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 cm(3) vs. PTSO: 0.44 ± 0.35 cm(3); 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.