Patterns of Peripheral Blood B-Cell Subtypes Are Associated With Treatment Response in Patients Treated With Immune Checkpoint Inhibitors: A Prospective Longitudinal Pan-Cancer Study.

Autor:	Barth DA; Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria., Stanzer S; Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria., Spiegelberg JA; Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria., Bauernhofer T; Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria., Absenger G; Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria., Szkandera J; Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria., Gerger A; Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria., Smolle MA; Department of Orthopaedics and Trauma, Medical University of Graz, Graz, Austria., Hutterer GC; Department of Urology, Medical University of Graz, Graz, Austria., Ahyai SA; Department of Urology, Medical University of Graz, Graz, Austria., Madl T; Gottfried Schatz Research Center, Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.; BioTechMed-Graz, Graz, Austria., Posch F; Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria., Riedl JM; Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria., Klec C; Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria., Jost PJ; Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria., Kargl J; Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.; Otto Loewi Research Center, Division of Pharmacology, Medical University of Graz, Graz, Austria., Stradner MH; Division of Rheumatology and Immunology, Department of Internal Medicine, Medical University of Graz, Graz, Austria., Pichler M; Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.; Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Apr 01; Vol. 13, pp. 840207. Date of Electronic Publication: 2022 Apr 01 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.840207
Abstrakt:	Background: Immune checkpoint inhibitors (ICIs) have revolutionized systemic anti-tumor treatments across different types of cancer. Nevertheless, predictive biomarkers regarding treatment response are not routinely established yet. Apart from T-lymphocytes, the humoral immunity of B-lymphocytes is studied to a substantially lesser extent in the respective setting. Thus, the aim of this study was to evaluate peripheral blood B-cell subtypes as potential predictors of ICI treatment response. Methods: Thirty-nine cancer patients receiving ICI therapy were included into this prospective single-center cohort study. All had a first blood draw at the date before treatment initiation and a second at the time of first response evaluation (after 8-12 weeks). Seven different B-cell subtypes were quantified by fluorescence-activated cell sorting (FACS). Disease control- (DCR) and objective response rate (ORR) were co-primary study endpoints. Results: Overall, DCR was 48.7% and ORR was 25.6%, respectively. At baseline, there was no significant association of any B-cell subtype with neither DCR nor ORR. At the first response evaluation, an increase in the frequency of CD21 - B-cells was a statistically significant negative predictor of response, both regarding DCR (OR=0.05, 95%CI=0.00-0.67, p =0.024) and ORR (OR=0.09, 95%CI=0.01-0.96, p =0.046). An increase of the frequency of switched memory B-cells was significantly associated with reduced odds for DCR (OR=0.06, 95%CI=0.01-0.70, p =0.025). Patients with an increased frequency of naïve B-cells were more likely to benefit from ICI therapy as indicated by an improved DCR (OR=12.31, 95%CI=1.13-134.22, p =0.039). Conclusion: In this study, certain B-cell subpopulations were associated with ICI treatment response in various human cancer types. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Barth, Stanzer, Spiegelberg, Bauernhofer, Absenger, Szkandera, Gerger, Smolle, Hutterer, Ahyai, Madl, Posch, Riedl, Klec, Jost, Kargl, Stradner and Pichler.)
Databáze:	MEDLINE
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