4.3 Article

Lymphocyte activation gene-3 is associated with programmed death-ligand 1 and programmed cell death protein 1 in small cell lung cancer

Journal

ANNALS OF TRANSLATIONAL MEDICINE
Volume 9, Issue 18, Pages -

Publisher

AME PUBLISHING COMPANY
DOI: 10.21037/atm-21-4481

Keywords

Lymphocyte activation gene-3 (LAG3); small cell lung cancer (SCLC); immunotherapy; programmed death-ligand 1 (PD-L1); programmed cell death protein 1 (PD-1)

Funding

  1. National Natural Science Foundation of China [81802255]
  2. Clinical Research Project of Shanghai Pulmonary Hospital [FKLY20010, FK18005]
  3. Young Talents in Shanghai
  4. 'Dream Tutor' Outstanding Young Talents Program [fkyq1901]
  5. Project of Shanghai Municipal Science and Technology Commission
  6. Scientific Research Project of Shanghai Pulmonary Hospital [fkcx1903]
  7. Shanghai Municipal Commission of Health and Family Planning [2017YQ050]
  8. Innovation Training Project of SITP of Tongji University
  9. Youth Project of Hospital Management Research Fund of Shanghai Hospital Association [Q1902037]
  10. National Key R&D Program of China [2018YFC0910500]
  11. Neil Shen's SJTU Medical Research Fund
  12. Key Projects of Leading Talent [19411950300]
  13. Key Discipline in 2019 (Oncology)

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This study demonstrated that LAG3 is an important immune checkpoint closely associated with PD-1/PD-L1, and may be a promising novel immunotherapy target for SCLC.
Background: In recent years, immunotherapy has achieved notable success in cancer treatment. Indeed, the novel immune checkpoint lymphocyte activation gene-3 (LAG3) has shown promising therapeutic efficacy in non-small cell lung cancer. However, it is unclear about the role of LAG3 in immunotherapy and survival in small cell lung cancer (SCLC). Methods: The expression of LAG3 in SCLC was evaluated in four public datasets. The association of LAG3 with programmed death-ligand 1 (PD-L1), programmed cell death protein 1 (PD-1), and overall survival (OS) was investigated. The LAG3-related biological processes and pathways were identified by functional analyses. Results: LAG3 expression was detected in SCLC tumor tissues. In the cBioPortal dataset with 81 clinical SCLC samples, LAG3 expression was markedly associated with PD-1 and PD-L1 expression (both P<0.050). In addition, Patients with high LAG3 expression had a trend toward a better OS (P=0.073). A similar survival trend was also observed in the GSE60052 dataset. Significantly, LAG3 expression was related to immune-related biological processes, such as immune response, antigen processing and presentation, and T cell co-stimulation (all P<0.001). Conclusions: This study demonstrated that LAG3 is an important immune checkpoint that is closely associated with PD-1/PD-L1. LAG3 may be a promising novel immunotherapy target for SCLC.

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