sLAG-3 in non-small-cell lung cancer patients’ serum

Background Anti-programmed cell death-1/programmed cell death ligand-1 monoclonal antibodies have been widely used in non-small-cell lung cancer (NSCLC), but not every patient can get benefits from them. Whether other molecular markers can predict the results of programmed cell death-1/programmed cell death ligand-1 inhibitors need to be explored. Lymphocyte-activation gene-3 (LAG-3) is another important immune checkpoint, which can inhibit tumor immunity. Soluble LAG-3 (sLAG-3) plays different functions from LAG-3. In this study, we detected the serum sLAG-3 level in NSCLC patients. Methods sLAG-3 was detected in 247 hospitalized patients by enzyme-linked immunosorbent assay. Every sample was repeated three times. Results Two-hundred forty-seven hospitalized patients were enrolled in this study. Of them, 71 had benign diseases and 176 were NSCLC patients. sLAG-3 in NSCLC serum was correlated with NSCLC stage. The sLAG-3 levels were significantly higher in stage I–II NSCLC than in stage III–IV (p<0.001). Conclusion The advanced NSCLC had the lower sLAG-3 expression. This might be related to the poor cancer immune response. Increasing sLAG-3 level might be a promising treatment in advanced NSCLC patients.

[1]  Xifeng Wu,et al.  Soluble immune checkpoint-related proteins as predictors of tumor recurrence, survival, and T cell phenotypes in clear cell renal cell carcinoma patients , 2019, Journal of Immunotherapy for Cancer.

[2]  Wanqing Chen,et al.  [Lung cancer incidence and mortality in China in 2013]. , 2017, Zhonghua zhong liu za zhi [Chinese journal of oncology].

[3]  F. Hirsch,et al.  LAG‐3 Protein Expression in Non–Small Cell Lung Cancer and Its Relationship with PD‐1/PD‐L1 and Tumor‐Infiltrating Lymphocytes , 2017, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[4]  J. Wargo,et al.  Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy , 2017, Cell.

[5]  Y. Shentu,et al.  Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. , 2016, The New England journal of medicine.

[6]  Y. Shentu,et al.  Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial , 2016, The Lancet.

[7]  A. Jemal,et al.  Cancer statistics in China, 2015 , 2016, CA: a cancer journal for clinicians.

[8]  Shohei Koyama,et al.  Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints , 2016, Nature Communications.

[9]  C. Rudin,et al.  Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. , 2015, The New England journal of medicine.

[10]  L. Crinò,et al.  Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. , 2015, The New England journal of medicine.

[11]  H. Saito,et al.  Upregulation of Immune Checkpoint Molecules, PD-1 and LAG-3, on CD4+ and CD8+ T Cells after Gastric Cancer Surgery , 2015, Yonago acta medica.

[12]  Jie He,et al.  Lung cancer incidence and mortality in China, 2009 , 2013, Thoracic cancer.

[13]  L. Yao,et al.  Expression of LAG-3 is coincident with the impaired effector function of HBV-specific CD8(+) T cell in HCC patients. , 2013, Immunology letters.

[14]  Kumar Kuna,et al.  Research Highlights and Editors’ Picks , 2013 .

[15]  P. Klenerman.  Faculty Opinions recommendation of Therapeutic blockade of PD-L1 and LAG-3 rapidly clears established blood-stage Plasmodium infection. , 2012 .

[16]  N. Pennell.  Integration of EGFR inhibitors and conventional chemotherapy in the treatment of non-small-cell lung cancer. , 2011, Clinical lung cancer.

[17]  Jun Ma,et al.  Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. , 2011, The Lancet. Oncology.

[18]  G. Giaccone,et al.  American Society of Clinical Oncology provisional clinical opinion: epidermal growth factor receptor (EGFR) Mutation testing for patients with advanced non-small-cell lung cancer considering first-line EGFR tyrosine kinase inhibitor therapy. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  F. Triebel.  LAG-3: a regulator of T-cell and DC responses and its use in therapeutic vaccination. , 2003, Trends in immunology.

[20]  S. Buisson,et al.  MHC class II signal transduction in human dendritic cells induced by a natural ligand, the LAG-3 protein (CD223). , 2003, Blood.

[21]  S. Buisson,et al.  MHC class II engagement by its ligand LAG-3 (CD223) leads to a distinct pattern of chemokine and chemokine receptor expression by human dendritic cells. , 2003, Vaccine.

[22]  P. Gaulard,et al.  T Lymphocytes infiltrating various tumour types express the MHC class II ligand lymphocyte activation gene-3 (LAG-3): role of LAG-3/MHC class II interactions in cell-cell contacts. , 2001, European journal of cancer.