Interferon-α and thymosin-α1 plus tislelizumab enhance CD8T cell cytotoxicity toward pancreatic ductal adenocarcinoma.

iScience2025PMID: 40727936

View on PubMed DOI: 10.1016/j.isci.2025.113053

Plain Language Summary

Researchers tested whether combining interferon-alpha and thymosin alpha-1 with the immunotherapy drug tislelizumab could improve immune cell attacks on pancreatic cancer cells. The combination treatment significantly outperformed tislelizumab alone, boosting CD8+ T-cell growth, cytokine production, and tumor-killing ability both in laboratory experiments and in animal models. This three-drug combination represents a promising strategy for improving immunotherapy effectiveness against pancreatic cancer, which is notoriously resistant to immune-based treatments.

Abstract

The strong immunosuppression and immune evasion of pancreatic ductal adenocarcinoma (PDAC) result in poor efficacy of immune checkpoint blockade. In this study, the PD-1 level on CD8T cells in the peripheral blood of patients with PDAC was significantly greater than that in the peripheral blood of healthy individuals. To enhance the anticancer activity of adoptive CD8T cells toward PDAC, interferon-α (IFN-α) and thymosin-α1 (Tα1) plus tislelizumab were preclinically explored. Compared with those of tislelizumab monotherapy, the proliferation and cytokine secretion of CD8T cells and the cytotoxic activity toward PDAC cells were significantly greater with the combination treatment of IFN-α and Tα1 plus tislelizumab. Moreover, the growth of PDAC tumors was inhibited by CD8T cells with high efficacy under the combination treatment. Thus, IFN-α and Tα1 plus tislelizumab enhance the anticancer activity of CD8T cells toward PDAC, representing an alternative strategy for improving cancer immunotherapy.

Authors

Deng, Shun; Deng, Rilin; Wang, Jinfeng; Hu, Qi; Xu, Biaoming; Zheng, Jinhai; Peng, Mingjing; Tan, Wenzhi; Zhu, Haizhen; Zuo, Chaohui

Keywords

Immunologycancer