AUTHOR=Barth Dominik A. , Stanzer Stefanie , Spiegelberg Jasmin A. , Bauernhofer Thomas , Absenger Gudrun , Szkandera Joanna , Gerger Armin , Smolle Maria A. , Hutterer Georg C. , Ahyai Sascha A. , Madl Tobias , Posch Florian , Riedl Jakob M. , Klec Christiane , Jost Philipp J. , Kargl Julia , Stradner Martin H. , Pichler Martin 

TITLE=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

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.840207

DOI=10.3389/fimmu.2022.840207

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>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<sup>-</sup> B-cells was a statistically significant negative predictor of response, both regarding DCR (OR=0.05, 95%CI=0.00-0.67, <italic>p</italic>=0.024) and ORR (OR=0.09, 95%CI=0.01-0.96, <italic>p</italic>=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, <italic>p</italic>=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, <italic>p</italic>=0.039).</p></sec><sec><title>Conclusion</title><p>In this study, certain B-cell subpopulations were associated with ICI treatment response in various human cancer types.</p></sec>