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

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

  • Biochim Biophys Acta Mol Basis Dis. 2024 May 28;1870(7):167262. doi: 10.1016/j.bbadis.2024.167262.
Qi Liu 1,  Xuxin Chen 2,  Man Qi 3,  Yongqun Li 2,  Wei Chen 2,  Caiyun Zhang 4,  Jiaxin Wang 4,  Zhihai Han 5,  Chunyang Zhang 6
Affiliations

Affiliations

  • 1 Department of Pulmonary and Critical Care Medicine, The Sixth Medical Center of Chinese PLA General Hospital, Beijing 100048, China; Navy Clinical College, the Fifth School of Clinical Medicine, Anhui Medical University, Hefei 230032, Anhui Province, China.
  • 2 Department of Pulmonary and Critical Care Medicine, The Sixth Medical Center of Chinese PLA General Hospital, Beijing 100048, China; College of Pulmonary & Critical Care Medicine, Chinese PLA General Hospital, Beijing 100091, China.
  • 3 Department of Pulmonary and Critical Care Medicine, The Sixth Medical Center of Chinese PLA General Hospital, Beijing 100048, China; College of Pulmonary & Critical Care Medicine, Chinese PLA General Hospital, Beijing 100091, China; Beijing Key Laboratory of OTIR, Beijing 100091, China.
  • 4 Department of Pulmonary and Critical Care Medicine, The Sixth Medical Center of Chinese PLA General Hospital, Beijing 100048, China.
  • 5 Department of Pulmonary and Critical Care Medicine, The Sixth Medical Center of Chinese PLA General Hospital, Beijing 100048, China; College of Pulmonary & Critical Care Medicine, Chinese PLA General Hospital, Beijing 100091, China; Beijing Key Laboratory of OTIR, Beijing 100091, China; Navy Clinical College, the Fifth School of Clinical Medicine, Anhui Medical University, Hefei 230032, Anhui Province, China. Electronic address: hanzhihai@301hospital.com.cn.
  • 6 Department of Pulmonary and Critical Care Medicine, The Sixth Medical Center of Chinese PLA General Hospital, Beijing 100048, China; College of Pulmonary & Critical Care Medicine, Chinese PLA General Hospital, Beijing 100091, China. Electronic address: zhcy101@126.com.
PMID: 38815768 DOI: 10.1016/j.bbadis.2024.167262
Abstract

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.

Keywords

Combination therapy; Cryoablation; Immune checkpoint inhibitors; Immunotherapy; Tumor immunity.

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