2. Academic Validation
  3. Anlotinib enhances the antitumor immunity of radiotherapy by activating cGAS/STING in non-small cell lung cancer

Anlotinib enhances the antitumor immunity of radiotherapy by activating cGAS/STING in non-small cell lung cancer

  • Cell Death Discov. 2022 Nov 28;8(1):468. doi: 10.1038/s41420-022-01256-2.
Dong Han # 1,  Jiajia Zhang # 2,  Yawei Bao 3,  Lei Liu 4,  Ping Wang 5,  Dong Qian 6
Affiliations

Affiliations

  • 1 Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Immunology and Biotherapy, 300060, Tianjin, China.
  • 2 Department of Radiation Oncology, YanTai Yuhuangding Hospital, 264000, Yantai, Shandong, China.
  • 3 Department of Radiation Oncology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, 230001, Hefei, Anhui, P.R. China.
  • 4 Department of Radiation Oncology, the First Affiliated Hospital of USTC, 230001, Hefei, Anhui, P.R. China.
  • 5 Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Immunology and Biotherapy, 300060, Tianjin, China. [email protected].
  • 6 Department of Radiation Oncology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, 230001, Hefei, Anhui, P.R. China. [email protected].
  • # Contributed equally.
PMID: 36443299 DOI: 10.1038/s41420-022-01256-2
Abstract

Radiation resistance and unsatisfactory efficacy of radioimmunotherapy are important barriers to non-small cell lung Cancer (NSCLC) treatment. The impacts of anlotinib on radiation and tumor immune microenvironment (TIME) in NSCLC remain to be resolved. Here, we find anlotinib enhances radiosensitivity, and further increases radiotherapy-stimulated CD8+ T cell infiltration and activation via triggering cGAS/STING pathway. Moreover, anlotinib shows significant effects on radioimmunotherapy (radiotherapy plus anti-PD-L1). The addition of anlotinib alleviates CD8+ T cell exhaustion, promotes the cytotoxicity and proliferation of CD8+ T cells, and boosts immune memory activation. Our work reveals the crucial role of anlotinib in antitumor immunity, and provides preclinical evidence for the application of anlotinib combined with radioimmunotherapy in NSCLC treatment.

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