Identification of PD1-mediated regulation of antitumor antigen response in patients with NSCLC using the trans vivo DTH assay
| Autor: | Ewa Jankowska-Gan, Ticiana Leal, William J. Burlingham, Diego A Lema, Nan Sethakorn |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Cancer Research Lung Neoplasms Programmed Cell Death 1 Receptor Immunology Short Report Mice Immune system Antigen biomarkers tumor Carcinoma Non-Small-Cell Lung Animals Humans Immunology and Allergy Medicine In patient Lung cancer Aged Pharmacology biology business.industry Cancer medicine.disease costimulatory and inhibitory T-cell receptors Phenotype Blockade Oncology Cancer research biology.protein Molecular Medicine Female Antibody business |
| Zdroj: | Journal for Immunotherapy of Cancer |
| ISSN: | 2051-1426 |
| Popis: | ObjectivesEmerging evidence has shown a role for tumor antigen-specific regulation in cancer. Identifying individuals with pre-existing regulatory responses may be key to understand those who are more likely to respond to Programmed Death-1 (PD-1) or PD-1 Ligand 1 (PD-L1) checkpoint blockade. We hypothesized that a functional assay could identify the role of PD-1/PD-L1 interactions on tumor-specific immune cells in the peripheral blood in patients with advanced non-small-cell lung cancer (NSCLC).MethodsWe performed the trans vivo delayed-type hypersensitivity assay to identify the role of PD-1/PD-L1-mediated tumor-specific immune regulation in ten patients with advanced NSCLC.ResultsThe majority of patients had PD-1-mediated anergic immune responses towards their tumor antigens. Eight out of nine of these patients did not respond to their own tumor antigens but responded in the presence of anti-PD-1 antibody (‘PD-1 anergy’ phenotype). A minority (3/9) also had ‘active’ PD-1-mediated immune suppressive regulatory responses. Our results suggest that PD-1-anergy is a common feature of NSCLC immune responses, whereas PD-1-mediated immune suppression is present only in a minority of patients. The latter was associated with poor clinical outcomes in our sample.ConclusionsOverall, our results indicate that bystander suppression or the ‘anergy-only’ phenomenon may be novel biomarkers in NSCLC and suggest prediction value based on these phenotypes. |
| Databáze: | OpenAIRE |
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