2. Academic Validation
  3. Interferon-α and thymosin-α1 plus tislelizumab enhance CD8+ T cell cytotoxicity toward pancreatic ductal adenocarcinoma

Interferon-α and thymosin-α1 plus tislelizumab enhance CD8+ T cell cytotoxicity toward pancreatic ductal adenocarcinoma

  • iScience. 2025 Jul 3;28(8):113053. doi: 10.1016/j.isci.2025.113053.
Shun Deng 1,  Rilin Deng 2 3,  Jinfeng Wang 1,  Qi Hu 4,  Biaoming Xu 4,  Jinhai Zheng 5,  Mingjing Peng 1,  Wenzhi Tan 6,  Haizhen Zhu 7,  Chaohui Zuo 1
Affiliations

Affiliations

  • 1 Department of Gastroduodenal and Pancreatic Surgery, Translational Medicine Joint Research Center of Liver Cancer, Laboratory of Digestive Oncology, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Clinical Research Center For Tumor of Pancreaticobiliary Duodenal Junction In Hunan Province, Changsha 410013, Hunan, China.
  • 2 School of Pharmaceutical Sciences, Hunan Normal University, Changsha 410013, Hunan, China.
  • 3 The Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Hunan Normal University Health Science Center, Changsha 410013, Hunan, China.
  • 4 Graduate Collaborative Training Base of Hunan Cancer Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China.
  • 5 School of Biomedical Sciences, Hunan University, Changsha 410082, Hunan, China.
  • 6 School of Food Science and Bioengineering, Changsha University of Science & Technology, Changsha 410114, Hunan, China.
  • 7 Key Laboratory of Tropical Translational Medicine of Ministry of Education, Department of Pathogen Biology, School of Basic Medicine and Life Science, Department of Clinical Laboratory of the Second Affiliated Hospital, The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, The Second Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, Hainan, China.
PMID: 40727936 DOI: 10.1016/j.isci.2025.113053
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 CD8+ T 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 CD8+ T 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 CD8+ T 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 CD8+ T cells with high efficacy under the combination treatment. Thus, IFN-α and Tα1 plus tislelizumab enhance the Anticancer activity of CD8+ T cells toward PDAC, representing an alternative strategy for improving Cancer Immunotherapy.

Keywords

Immunology; cancer.

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