Combined cryoablation and PD-1 inhibitor synergistically enhance antitumor immune responses in Lewis lung adenocarcinoma mice via the PI3K/AKT/mTOR pathway

• Published in: Biochimica et biophysica acta. Molecular basis of disease Vol. 1870; no. 7; p. 167262
• Main Authors: Liu, Qi, Chen, Xuxin, Qi, Man, Li, Yongqun, Chen, Wei, Zhang, Caiyun, Wang, Jiaxin, Han, Zhihai, Zhang, Chunyang
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2024
• Subjects: Adenocarcinoma of Lung - drug therapy; Adenocarcinoma of Lung - immunology; Adenocarcinoma of Lung - metabolism; Adenocarcinoma of Lung - pathology; Adenocarcinoma of Lung - surgery; Animals; Carcinoma, Lewis Lung - drug therapy; Carcinoma, Lewis Lung - immunology; Carcinoma, Lewis Lung - pathology; Cell Line, Tumor; Combination therapy; Combined Modality Therapy; Cryoablation; Cryosurgery - methods; Female; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - pharmacology; Immune Checkpoint Inhibitors - therapeutic use; Immunotherapy; Lung Neoplasms - drug therapy; Lung Neoplasms - immunology; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Mice; Mice, Inbred C57BL; Phosphatidylinositol 3-Kinases - metabolism; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Programmed Cell Death 1 Receptor - immunology; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction - drug effects; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; TOR Serine-Threonine Kinases - antagonists & inhibitors; TOR Serine-Threonine Kinases - metabolism; Tumor immunity; Cryoablation; Immune checkpoint inhibitors; Tumor immunity; Combination therapy; Immunotherapy
• ISSN: 0925-4439; 1879-260X; 1879-260X
• DOI: 10.1016/j.bbadis.2024.167262

Cryoablation is a therapeutic modality for lung adenocarcinoma that destroys target tumors using lethal levels of cold, resulting in the release of large amounts of specific antigens that activate immune responses. However, tumor immune checkpoint escape mechanisms prevent these released self-antigens from inducing effective anti-tumor immune responses. To overcome this challenge, we propose the use of immune checkpoint inhibitors to relieve T cell inhibition by immune checkpoints and enhance the anti-tumor immune response mediated by cryoablation. We used bilateral tumor-bearing mouse models and a specific cryoablation instrument to study the efficacy of cryoablation combined with PD-1 inhibitors in Lewis lung adenocarcinoma model mice. We found that cryoablation combined with PD-1 inhibitors significantly inhibited the growth of mouse lung adenocarcinoma, prolonged mouse survival, and enhanced the anti-tumor immune response. Moreover, this combined regimen could synergistically promote the activation and proliferation of T cells via the PI3K/AKT/mTOR pathway. The present study provides a strong theoretical basis for the clinical combination of cryoablation and PD-1 inhibitors. •Cryoablation combined with PD-1 inhibitor synergistically treats Lewis lung cancer in mice.•Combined therapy enhances anti-tumor immune response.•Combined therapy promotes T-cell proliferation via the PI3K/AKT/mTOR pathway.