T-cell diversification reflects antigen selection in the blood of patients on immune checkpoint inhibition and may be exploited as liquid biopsy biomarker
| Autor: | Toni Thenhausen, Nuray Akyüz, Thorben Mährle, Sonja Loges, Eray Goekkurt, Julia Quidde, Alexander Stein, Carsten Bokemeyer, Benjamin Thiele, Anna Brandt, Simon Schliffke, Janina Radloff, Thomas Haalck, Mascha Binder, Anne Marie Asemissen, Christopher Thomas Ford, Artus Krohn-Grimberghe |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research biology T cell medicine.medical_treatment Immunotherapy Immune checkpoint 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Immune system Oncology Cancer immunotherapy Antigen 030220 oncology & carcinogenesis Immunology medicine biology.protein Liquid biopsy Antibody |
| Zdroj: | International Journal of Cancer. 140:2535-2544 |
| ISSN: | 0020-7136 |
| Popis: | Cancer immunotherapy with antibodies targeting immune checkpoints, such as programmed cell death protein 1 (PD-1), shows encouraging results, but reliable biomarkers predicting response to this costly and potentially toxic treatment approach are still lacking. To explore an immune signature predictive for response, we performed liquid biopsy immunoprofiling in 18 cancer patients undergoing PD-1 inhibition before and shortly after initiation of treatment by multicolor flow cytometry and next-generation T- and B-cell immunosequencing (TCRs/IGH). Findings were correlated with clinical outcomes. We found almost complete saturation of surface PD-1 on all T-cell subsets after the first dose of the antibody. Both T- and B-cell compartments quantitatively expanded during treatment. These expansions were mainly driven by an increase in the activated T-cell compartments, as well as of naive B- and plasma cells. Deep immunosequencing revealed a clear diversification pattern of the clonal T-cell space indicative of antigenic selection in 47% of patients, while the remaining patients showed stable repertoires. 43% of the patients with a diversification pattern showed disease control in response to the PD-1 inhibitor. No disease stabilizations were observed without clonal T-cell space diversification. Our data show for the first time a clear impact of PD-1 targeting not only on circulating T-cells, but also on B-lineage cells, shedding light on the complexity of the anti-tumor immune response. Liquid biopsy T-cell next-generation immunosequencing should be prospectively evaluated as part of a composite response prediction biomarker panel in the context of clinical studies. |
| Databáze: | OpenAIRE |
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