Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Barth, D.
Prospective evaluation of autoantibodies and peripheral blood B-cell subtypes as predictive biomarkers in cancer patients undergoing palliative treatment with immune checkpoint inhibitors.
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Medizinische Universität Graz; 2023. pp. 96
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Klec Christiane
- Pichler Martin
- Stradner Martin Helmut
- Altmetrics:
- Abstract:
- Introduction: Reinduction of anti-cancer immune responses by the means of immune checkpoint inhibitors (ICIs) have greatly impacted systemic cancer treatment across cancer types in the last decade. Focus in research has been primarily on T-cell responses upon ICI therapy, while B-cells, despite being an important part of adaptive immunity through their ability of antigen presentation and antibody production, have been studied to a lesser extent. The presence of autoantibodies in cancer patients undergoing ICI treatment has been suggested as markers for response prediction, yet evidence is inconclusive and prospective studies are missing. Moreover, a longitudinal characterization of circulating B-cell subtypes during ICI therapy has been missing. The aim of this study was to fill this gap, and evaluate both, autoantibodies and circulating B-cell subtypes as markers for treatment response in patients undergoing ICI therapy within a prospective longitudinal biomarker study. Methods: Forty-four cancer patients who were treated with mono- or combination ICI treatment were included in this prospective single-center cohort study. Autoantibody titers, including ANA, ENA, rheumatoid arthritis-, hepatopathy-, and myositis-associated autoantibodies, as well as seven different B-cell subtypes, quantified by fluorescence-activated cell sorting (FACS), were determined at the timepoint before ICI treatment start, and after 8-12 weeks of ICI therapy at the timepoint of first response evaluation. Disease-control rate (DCR) and objective response rate (ORR) were primary endpoints for the analysis of both, autoantibody and B-cells, while progression-free survival (PFS) and the development of immune-related adverse events (irAEs) were co-secondary endpoints in the evaluation of autoantibodies. Results: Autoantibodies at baseline as well as after 8-12 weeks of ICI therapy did not predict ICI treatment efficacy, as indicated by DCR, ORR and PFS. Furthermore, no significant association with the rate of irAEs could be observed. As for circulating B-cell subtypes, at baseline, there was no significant relationship between different B-cell subtypes and response parameters. After 8-12 weeks of ICI therapy, an increase in the frequency of CD21- or switched memory B-cells was significantly associated with decreased odds of response as for both, DCR and ORR (all p<0.05). Conversely, response rates were higher patients who and an increase in the frequency of naïve B-cells upon ICI treatment (p=0.039). Conclusion: In this study, no association of autoantibodies, neither at baseline nor after treatment start of ICIs, with parameters of response or with irAEs could be observed. However, an increase of certain peripheral blood B-cell subtypes, namely CD21-, switched memory and naïve B-cells, were associated with response. This is the first study to link CD21- B-cells, which represent an anergic and exhausted B-cell population, with ICI treatment efficacy.