Focus |

Cancer immunotherapy

Cancer immunotherapy – the targeting or use of immune system components to kill tumour cells – can take many forms, including antibodies, vaccines and T cells. This Focus issue from Nature Reviews Immunology features three Review articles that highlight some of the most promising recent developments in this field: the use of checkpoint inhibitors for molecules such as PD1; the drive towards increased personalization of tumour vaccines; and the use of vaccines for prevention as well as cure. In addition, three Opinion articles discuss how the local tumour microenvironment can be manipulated to improve the efficacy of immunotherapy, by normalizing the tumour vasculature, through local immunomodulation using synthetic, scaffold-based immune niches, and by targeting tumour glycosylation. 

Reviews & Perspectives

In this Review, the authors detail the complex expression patterns and regulation of programmed cell death protein 1 (PD1) and its ligands. The authors focus on the importance of understanding these pathways in order to optimize the efficiency and safety of immune checkpoint blockade in patients.

Review Article | | Nature Reviews Immunology

Normalization of the tumour vasculature can improve immune effector cell infiltration, leading to immunotherapy potentiation. In this Opinion article, Huang et al. propose that reciprocal regulation between tumour vascular normalization and immune reprogramming forms a positive feedback loop that can induce durable antitumour immunity within the tumour microenvironment.

Opinion | | Nature Reviews Immunology

Carl Figdor and colleagues propose that delivering cancer immunotherapy in the context of engineered three-dimensional scaffolds may boost anticancer immunity. The synthetic scaffolds, which can be linked to immunomodulatory factors, can act as immune niches to support the priming and maintenance of antitumour immune responses.

Opinion | | Nature Reviews Immunology

News & Comment

Additional content

CD8+ T cell differentiation and function are regulated by epigenetic changes mainly including DNA methylation, histone modification and modification of chromatin architecture. As described here, a detailed understanding of these epigenetic mechanisms can be harnessed to improve T cell-based immunotherapies.

Review Article | | Nature Reviews Immunology

Initiation of an adaptive immune response depends on the detection of both antigenic epitopes and adjuvant signals. Infectious pathogens and cancer cells often avoid immune detection by limiting the release of danger signals from dying cells. When is cell death immunogenic and what are the pathophysiological implications of this process?

Review Article | | Nature Reviews Immunology

In this Review, the authors summarize the features and the molecular drivers of T cell dysfunction in cancer and compare these with dysfunctional T cells in chronic viral infection. The metabolic competition in the tumour microenvironment is also discussed. Understanding antitumour T cell responses has important implications for cancer immunotherapy.

Review Article | | Nature Reviews Immunology

In addition to avoiding immune attack in the primary tumour, metastatic cancer cells can harness suppressive immune cells to help promote and protect them from immune surveillance as they travel from the primary tumour site, through blood or lymphatic vessels, to the metastatic site. Thus, targeting pro-metastatic immune cells may offer new therapeutic strategies for treating the major cause of death from cancer — metastatic disease.

Review Article | | Nature Reviews Immunology

γδ T cells have unique specificities, high clonal frequencies and a pre-activated differentiation status that allow rapid and non-redundant responses to tumours. Here, the authors review their often contrasting roles in cancer and the opportunities for γδ T cell-based cancer therapies.

Review Article | | Nature Reviews Immunology

Type I interferons (IFNs) are best known for their role in antiviral immunity. As discussed in this Review, recent evidence indicates that these cytokines also have an integral role in natural and therapy-induced anticancer immunity. Harnessing the antineoplastic properties of type I IFNs may lead to the development of ever-more effective anticancer therapies.

Review Article | | Nature Reviews Immunology

Exhausted T cells display a phenotype characterized by progressive loss of function, and they can develop following exposure to persistent antigen and/or inflammatory signals during chronic viral infections or cancer. The authors describe the molecular mechanisms of T cell exhaustion and how the exhausted phenotype is different from other dysfunctional states of T cells.

Review Article | | Nature Reviews Immunology