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=Volume 11 - 2020

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 recognised, with reports of positive prognostic value ascribed to tumour-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-tumour roles of B cells. B cells appear to play an integral role in forming tumour-associated tertiary lymphoid structures (TLS) which can further modulate T cell activation. Expressed antibodies may distinctly influence tumour regulation in the tumour microenvironment, with some isotypes associated with strong anti-tumour immune response and others with progressive disease. Recently, B cells have been evaluated in the context of cancer immunotherapy. Checkpoint inhibitors (CPI), targeting T cell effector functions, have revolutionised 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 therapy. 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 optimise CPI therapy in melanoma.