AUTHOR=Willsmore Zena N. , Harris Robert J. , Crescioli Silvia , Hussein Khuluud , Kakkassery Helen , Thapa Deepika , Cheung Anthony , Chauhan Jitesh , Bax Heather J. , Chenoweth Alicia , Laddach Roman , Osborn Gabriel , McCraw Alexa , Hoffmann Ricarda M. , Nakamura Mano , Geh Jenny L. , MacKenzie-Ross Alastair , Healy Ciaran , Tsoka Sophia , Spicer James F. , Papa Sophie , Barber Linda , Lacy Katie E. , Karagiannis Sophia N. TITLE=B Cells in Patients With Melanoma: Implications for Treatment With Checkpoint Inhibitor Antibodies JOURNAL=Frontiers in Immunology VOLUME=11 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.622442 DOI=10.3389/fimmu.2020.622442 ISSN=1664-3224 ABSTRACT=

The contributions of the humoral immune response to melanoma are now widely recognized, with reports of positive prognostic value ascribed to tumor-infiltrating B cells (TIL-B) and increasing evidence of B cells as key predictors of patient response to treatment. There are disparate views as to the pro- and anti-tumor roles of B cells. B cells appear to play an integral role in forming tumor-associated tertiary lymphoid structures (TLSs) which can further modulate T cell activation. Expressed antibodies may distinctly influence tumor regulation in the tumor microenvironment, with some isotypes associated with strong anti-tumor immune response and others with progressive disease. Recently, B cells have been evaluated in the context of cancer immunotherapy. Checkpoint inhibitors (CPIs), targeting T cell effector functions, have revolutionized the management of melanoma for many patients; however, there remains a need to accurately predict treatment responders. Increasing evidence suggests that B cells may not be simple bystanders to CPI immunotherapy. Mature and differentiated B cell phenotypes are key positive correlates of CPI response. Recent evidence also points to an enrichment in activatory B cell phenotypes, and the contribution of B cells to TLS formation may facilitate induction of T cell phenotypes required for response to CPI. Contrastingly, specific B cell subsets often correlate with immune-related adverse events (irAEs) in CPI. With increased appreciation of the multifaceted role of B cell immunity, novel therapeutic strategies and biomarkers can be explored and translated into the clinic to optimize CPI immunotherapy in melanoma.