Immunity reloaded: Deconstruction of the PD-1 axis in B cell lymphomas

Over the past decade therapies targeting the PD-1 axis with monoclonal antibodies to reinstate host immune function have revolutionized the clinical management of some cancers but have had minimal impact on others. This dichotomy is exemplified by B cell lymphomas. Whilst striking results are observed in classical Hodgkin Lymphoma (cHL) and Primary Mediastinal B Cell Lymphoma (PMBL), responses in other B cell lymphomas are infrequent. Even with cHL and PMBL, responses are not always durable and adverse effects can result in treatment discontinuation. A more nuanced approach to manipulate the PD-1 axis is required before the full benefits of PD-1 axis blockade can be realised. In this review, we provide an outline of PD-1 axis biology, including the range of cellular expression, the molecular mechanisms underlying regulation and the impacts of downstream signalling. These may permit the development of alternate strategies to PD-1 axis blockade to enhance the therapeutic efficacy in B cell lymphomas.