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OX40 and LAG3 are associated with better prognosis in advanced gastric cancer patients treated with anti-programmed death-1 antibody
- Source :
- British Journal of Cancer
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- 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.
- Subjects :
- Adult
CD4-Positive T-Lymphocytes
Male
Cancer Research
LAG3
medicine.drug_class
Programmed Cell Death 1 Receptor
OX40 Ligand
CD8-Positive T-Lymphocytes
Monoclonal antibody
T-Lymphocytes, Regulatory
Article
Flow cytometry
Prognostic markers
03 medical and health sciences
0302 clinical medicine
Immune system
Antigens, CD
Stomach Neoplasms
medicine
Humans
Aged
030304 developmental biology
Aged, 80 and over
0303 health sciences
biology
medicine.diagnostic_test
business.industry
Middle Aged
Flow Cytometry
Prognosis
medicine.disease
Lymphocyte Activation Gene 3 Protein
Progression-Free Survival
Nivolumab
Oncology
030220 oncology & carcinogenesis
biology.protein
Cancer research
Female
Antibody
Gastric cancer
business
Progressive disease
CD8
Subjects
Details
- ISSN :
- 15321827 and 00070920
- Volume :
- 122
- Database :
- OpenAIRE
- Journal :
- British Journal of Cancer
- Accession number :
- edsair.doi.dedup.....92ffe52e7dfce2d83bdc5d71cc16cbf1