OX40 and LAG3 are associated with better prognosis in advanced gastric cancer patients treated with anti-programmed death-1 antibody.
Adult
Aged
Aged, 80 and over
Antigens, CD
/ genetics
CD4-Positive T-Lymphocytes
/ drug effects
CD8-Positive T-Lymphocytes
/ drug effects
Female
Flow Cytometry
Humans
Male
Middle Aged
Nivolumab
/ administration & dosage
OX40 Ligand
/ genetics
Prognosis
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
Progression-Free Survival
Stomach Neoplasms
/ drug therapy
T-Lymphocytes, Regulatory
/ drug effects
Lymphocyte Activation Gene 3 Protein
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
28
10
2019
accepted:
06
03
2020
revised:
12
02
2020
pubmed:
24
3
2020
medline:
23
12
2020
entrez:
24
3
2020
Statut:
ppublish
Résumé
Anti-PD-1 monoclonal antibody, nivolumab, has shown efficacy for advanced gastric cancer (AGC). However, the specific immune cell subsets predominantly activated during the period of anti-PD-1 therapy for AGC have not been clarified. Peripheral blood of 30 AGC patients treated with nivolumab was prospectively obtained before the initial and second administrations and at the time of progressive disease (PD). The proportions of immune cell subsets and the serum concentrations of cytokines were systematically analysed by flow cytometry. Associations of subsets and serum cytokines with therapeutic effects were evaluated. After the initial administration, significant increases in activated central/effector memory, activated effector T cells, and activated T-helper 1 subsets were observed. At the time of PD, activated regulatory T cells, LAG3-positive CD4+/CD8+ T cells, and TIM3-positive CD4+/CD8+ T cells increased significantly. Significant positive correlations were shown between progression-free survival and proportions of LAG3-positive CD4+/CD8+ T cells and of OX40-positive CD4+/CD8+ T cells (log-rank p = 0.0008, 0.0003, 0.0035 and 0.0040). Nivolumab therapy enhances activation of central/effector memory and effector subsets of CD4+/CD8+ T cells. The expression levels of LAG-3 and OX40 on T cells correlated with the efficacy of nivolumab therapy and could be reasonable biomarkers for anti-PD-1 therapy.
Sections du résumé
BACKGROUND
Anti-PD-1 monoclonal antibody, nivolumab, has shown efficacy for advanced gastric cancer (AGC). However, the specific immune cell subsets predominantly activated during the period of anti-PD-1 therapy for AGC have not been clarified.
METHODS
Peripheral blood of 30 AGC patients treated with nivolumab was prospectively obtained before the initial and second administrations and at the time of progressive disease (PD). The proportions of immune cell subsets and the serum concentrations of cytokines were systematically analysed by flow cytometry. Associations of subsets and serum cytokines with therapeutic effects were evaluated.
RESULTS
After the initial administration, significant increases in activated central/effector memory, activated effector T cells, and activated T-helper 1 subsets were observed. At the time of PD, activated regulatory T cells, LAG3-positive CD4+/CD8+ T cells, and TIM3-positive CD4+/CD8+ T cells increased significantly. Significant positive correlations were shown between progression-free survival and proportions of LAG3-positive CD4+/CD8+ T cells and of OX40-positive CD4+/CD8+ T cells (log-rank p = 0.0008, 0.0003, 0.0035 and 0.0040).
CONCLUSIONS
Nivolumab therapy enhances activation of central/effector memory and effector subsets of CD4+/CD8+ T cells. The expression levels of LAG-3 and OX40 on T cells correlated with the efficacy of nivolumab therapy and could be reasonable biomarkers for anti-PD-1 therapy.
Identifiants
pubmed: 32203221
doi: 10.1038/s41416-020-0810-1
pii: 10.1038/s41416-020-0810-1
pmc: PMC7217874
doi:
Substances chimiques
Antigens, CD
0
OX40 Ligand
0
PDCD1 protein, human
0
Programmed Cell Death 1 Receptor
0
TNFSF4 protein, human
0
Nivolumab
31YO63LBSN
Lymphocyte Activation Gene 3 Protein
0
Lag3 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1507-1517Références
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