Volume 18 Issue 6, June 2021

A recent meta-analysis examined and validated biomarkers of response to immune-checkpoint inhibitors (ICIs). Herein, we discuss the findings of this analysis, which are consistent with previously identified determinants of ICI efficacy and demonstrate that some genetic variables influence response across multiple cancer types.

An unfavourable gut bacterial composition has been shown to reduce the likelihood of clinical benefit from immune-checkpoint inhibitors (ICIs). The results of two first-in-human studies of faecal microbiota transplantation in patients with melanoma refractory to anti-PD-1 antibodies validate preclinical evidence that this approach can improve the gut microbiota and overcome resistance to ICIs; however, many questions remain.

Antibody–drug conjugates (ADCs) constitute a unique class of anticancer agents with demonstrated clinical efficacy against several different cancer types. Herein, the authors discuss the design and mechanisms of action of ADCs and how these properties are reflected in the clinical activity and toxicity profiles of such agents. Potential strategies to overcome the limitations of ADCs and thereby maximize their therapeutic benefit for patients with cancer are also proposed.

PD-L1 expression is currently the best available biomarker for the prediction of responsiveness to immune-checkpoint inhibitors. However, several immunohistochemical assays are now approved for clinical use in various settings, despite imperfect inter-assay concordance, with important implications for pathology services and, potentially, for clinical outcomes. In this Review, the authors compare the performance of the various FDA-approved PD-L1 assays, discuss the varying implications of PD-L1 expression across different tumour types and provide guidance on possible novel approaches that might optimize the clinical utility of PD-L1 as a biomarker.

A host of additional toxicities and/or potential late effects of chimeric antigen receptor (CAR) T cell therapy beyond cytokine release syndrome (CRS) warrant further investigation. Herein, experts in paediatric cell therapy, supportive care and/or study of late effects from cancer and haematopoietic stem cell transplantation present six key focus research areas related to CAR T cell-related outcomes beyond CRS.

CD19-specific chimeric antigen (CAR)-modified T cells are approved for patients with advanced-stage forms of certain B cell malignancies. However, a subset of patients will have anti-CAR immune responses, leading to a lack of CAR T cell persistence and a rapid loss of any antitumour efficacy. In this Review, the authors describe the extent of anti-CAR immune responses in patients and suggest measures that could be used to better monitor for these events. Additionally, they describe novel approaches to CAR T cell therapy that might reduce the risk of such responses in the future.