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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.
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.
Mouse and human tumour-associated macrophages express PD-1, which increases with cancer stage and induces decreased phagocytosis by macrophages; by contrast, PD-L1 removal increases phagocytosis in vivo, decreases tumour burden and increases survival of mice.
Rosenberg and colleagues review evidence suggesting that T cells that target tumor neoantigens arising from cancer mutations are the main mediators of many effective cancer immunotherapies in humans.
Introducing chimeric antigen receptors into the endogenous T-cell receptor locus reduces tonic signalling, averts accelerated T-cell differentiation and delays T-cell exhaustion, leading to enhanced function and anti-tumour efficacy compared to random integrations.
The clinical benefit of anti-PD-1 antibody treatment is dependent on the extent to which exhausted CD8 T cells are reinvigorated in relation to the tumour burden of the patient.
The authors describe a two-cell-type CRISPR screen to identify tumour-intrinsic genes that regulate the sensitivity of cancer cells to effector T cell function.
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.
Insights into the effects of targeted therapies, conventional chemotherapy and radiation therapy, on the induction of antitumour immunity will help to advance the design of combination strategies that increase the rate of complete and durable clinical responses in patients.
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.
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.