Nature Outlook |

Cancer immunotherapy

Drugs that mobilize our immune systems against cancer are dramatically improving care for many people, and research is rapidly moving ahead in the lab and the clinic.

This Nature Outlook is editorially independent. It is produced with third party financial support. About this content.

Features and comment

Thousands of clinical trials are unleashing the power of the body's own defences against tumours.

Outlook | | Nature

The next generation of modified T-cell therapies is taking on solid tumours — but it’s an uphill fight.

Outlook | | Nature

More from Nature Research

In this Perspective, June, Bluestone and Warshauer discuss potential cellular and molecular explanations for the autoimmunity often associated with immunotherapy, and propose additional research and changes to reporting practices to aid efforts to understand and minimize these toxic side effects.

Perspective | | Nature Medicine

Therapeutic antibodies that inhibit the interaction of programmed cell death protein (PD-1) with its ligand (PD-L1) are known to activate cytotoxic T cells. Here Irv Weissmann and colleagues study the role for PD-1 on tumour-infiltrating macrophages in mice. The study shows that PD-1-expressing macrophages have limited phagocytic capabilities and that blocking PD-1/PD-L1 enhances phagocytosis and correlates with reduced tumour growth. This finding suggests a T-cell-independent mechanism of therapeutic activity of PD-1/PD-L1 inhibitors which may be clinically relevant.

Letter | | Nature

Using T cells transduced with synthetic chimeric antigen receptors (CARs) is a promising strategy for treating certain types of cancer. Here Michel Sadelain and colleagues provide evidence in a mouse tumour model that knocking the CAR into the endogenous T-cell receptor α constant locus reduces tonic signalling, avoids accelerated T-cell differentiation, and delays T-cell exhaustion. This results in enhanced function and anti-tumour efficacy compared with random integrations.

Letter | | Nature

Only a small proportion of patients with advanced melanoma currently experience a long-term clinical benefit from therapeutic PD-1 blockade. Until now, blood-based profiling has not been widely explored as a means to understand the mechanisms of PD-1 blockade. In this study, Alexander Huang et al. analyse CD8 T cells in the blood and show that the clinical benefit of PD-1 blockade depends on the extent to which it reinvigorates exhausted CD8 T cells in relation to the pre-treatment tumour burden. Identifying the ratio of tumour burden to CD8 T-cell reinvigoration may help to predict how well a patient will respond to PD-1-blocking therapy.

Article | | Nature

Some mutations in cancer cells make them resistant to immunotherapy. Nicholas Restifo and colleagues designed a 'two-cell-type' CRISPR–Cas9 screen to identify tumour-intrinsic genetic mutations associated with the sensitivity of melanoma cells to effector T cell function. The candidate genes identified included mediators of MHC class I antigen presentation and genes unknown to be involved in these immunity processes. The authors highlight the interaction between T-cell-secreted apelin and its receptor APLNR on tumour cells as a node for potent T-cell-mediated killing of cancer cells.

Article | | Nature

The aim of immunotherapy is to treat cancer by enabling the immune system to attack the tumour. In the past decade, remarkable results have been obtained in clinical trials with immunotherapy for patients with advanced-stage cancer. Two types of immunotherapy have been used in the majority of trials conducted in the past decade: immune cell-targeted antibody therapy and adoptive cellular therapy. Herein, the latest advances in both modalities are discussed, including settings for which testing combination strategies and 'armoured' CAR T cells are recommended.

Review Article | | Nature Reviews Clinical Oncology

In this Review, Yarchoanet al. discuss the potential of targeting tumour-specific antigens (neoantigens) to increase antitumour immunity and present a framework for personalized cancer immunotherapy based on the identification and specific targeting of individual tumour neoantigens.

Review Article | | Nature Reviews Cancer

Immune checkpoint inhibition is a novel approach to cancer treatment with enormous potential to improve the outcomes of patients with a range of malignancies. However, owing to this novel approach, a range of adverse events have emerged with different aetiologies to those of more conventional cancer treatments. In this Review, the authors describe the occurrence, and optimal management of adverse events resulting from use of immune checkpoint inhibitors.

Review Article | | Nature Reviews Clinical Oncology