Immunomodulatory Function of Pien Tze Huang in T Cell-Mediated Anti-tumor Activity against B16–F10, MC38 and Hep1-6 Tumor Models

Objective To investigate the anti-tumor effects of Pien Tze Huang (PZH) in mouse models of B16–F10 melanoma, MC38 colorectal cancer, Hep1-6 hepatocellular carcinoma and chemically induced hepatocellular carcinoma model. Methods Various tumor models, including B16–F10, MC38 and Hep1-6 tumor hypodermic inoculation models, B16–F10 and Hep1-6 pulmonary metastasis models, Hep1-6 orthotopic implantation model, and chemically induced hepatocellular carcinoma model, were utilized to evaluate the anti-tumor function of PZH. Tumor growth was assessed by measuring tumor size and weight of solid tumors isolated from C57BL/6 mice. For cell proliferation and death of tumor cells in vitro , as well as T cell activation markers, cytokine production and immune checkpoints analysis, single-cell suspensions were prepared from mouse spleen, lymph nodes, and tumors after PZH treatment. Results PZH demonstrated significant therapeutic efficacy in inhibiting tumor growth ( P <0.01). Treatment with PZH resulted in a reduction in tumor size in subcutaneous MC38 colon adenocarcinoma and B16–F10 melanoma models, and decreased pulmonary metastasis of B16–F10 melanoma and Hep1-6 hepatoma ( P <0.01). However, in vitro experiments showed that PZH only had slight impact on the cell proliferation and survival of tumor cells ( P >0.05). Nevertheless, PZH exhibited a remarkable ability to enhance T cell activation and the production of interferon gamma, tumor necrosis factor alpha, and interleukin 2 in CD4 + T cells in vitro ( P <0.01 or P <0.05). Importantly, PZH substantially inhibited T cell exhaustion and boosted cytokine production by tumor-infiltrating CD8 + T cells ( P <0.01 or P <0.05). Conclusion This study has confirmed a novel immunomodulatory function of PZH in T cell-mediated anti-tumor immunity, indicating that PZH holds promise as a potential therapeutic agent for cancer treatment.