Immune-checkpoint inhibitors (ICI) constitute a paradigm shift in the treatment of non-small-cell lung cancer (NSCLC); however, identifying the minority of patients who derive long-term benefit remains problematic, particularly among those with targetable oncogenic drivers who have typically been under-represented in or excluded from clinical trials of ICIs. This Review summarizes the associations of common oncogenic drivers of NSCLC with sensitivity or resistance to ICIs as well as the underlying effects on the immune tumour microenvironment. Potential vulnerabilities that could potentially be exploited to overcome primary resistance to ICIs conferred by certain oncogenic drivers are also highlighted.

Oncolytic viruses (OVs) provide a novel cancer treatment strategy, with a mechanism of action and toxicity profiles that are distinctly different to those of more traditional therapies. Thus far, four OVs have entered clinical use globally, yet only talimogene laherparepvec (T-VEC) has entered widespread clinical use. In this Review, the authors describe the clinical and regulatory experience with T-VEC thus far, and how this can guide the development of novel OVs. Discussions of a range of novel OVs with the potential for clinical implementation in the near future are also provided.

γδ T cells are lymphocytes with properties of both typical αβ T cell and natural killer cells, notable tissue tropisms, and MHC-independent antitumour functions that make them attractive agents for cancer immunotherapy. In this Review, the authors provide an overview of human γδ T cell subsets, discuss the antitumour and pro-tumour activities of these cells and their prognostic value in patients with cancer, and describe the current landscape of γδ T cell-based immunotherapies.

Preclinical models that faithfully recapitulate interactions between the human immune system and tumours are necessary to evaluate human-specific immunotherapies in vivo; however, their number is currently limited. The authors of this Review discuss the currently available humanized mouse models, which are immunodeficient mice co-engrafted with human tumours and immune components, with a focus on their applicability in translational research.

In 2022, the FDA approved numerous new drug and biologic agents, including targeted small molecules, immunotherapeutics, a gene therapy and a radiopharmaceutical. Several drug development challenges were also addressed, and key focus areas for the FDA Oncology Center of Excellence included ongoing monitoring of the Accelerated Approval programme and drug dose optimization.