Reviews & Analysis

In the short time since SARS-CoV-2 infections emerged in humans, much has been learned about the immunological processes that underlie the clinical manifestation of COVID-19. Here, the authors provide an overview of the pathophysiology of SARS-CoV-2 infection and discuss potential therapeutic approaches.

Co-inhibitory receptor signalling — through CTLA4, LAG3, PD1, TIGIT, NRP1 and TIM3 — controls the function and stability of regulatory T cells in autoimmunity and cancer and could therefore be amenable to therapeutic targeting.

The RNA-sensing retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are important inducers of type I interferons and other antiviral immune mediators. Here, Jan Rehwinkel and Michaela Gack explain how members of the RLR family are regulated and reflect on the importance of the RLRs in viral infection, autoimmunity and cancer.

Here a group of leaders in the field define our current understanding of ‘trained immunity’, which refers to the memory-type responses that occur in the innate immune system. The authors discuss our current understanding of the key epigenetic and metabolic processes involved in trained immunity and consider its relevance in immune-mediated diseases and cancer.

Innate lymphoid cell (ILC) subsets with defined phenotypes can adapt to local environmental cues through transdifferentiation. Studies of such plasticity have improved our understanding of the biological roles of ILCs and offer promise for new strategies to treat inflammatory diseases and cancer.

Recent single-cell studies have revealed a previously unappreciated heterogeneity among endothelial cells that line the lymphatic sinuses of the lymph nodes. In this Review, the authors describe these various lymphatic endothelial cell types and how they support the trafficking of cells and antigens through lymph nodes.

Recently, antibody-mediated control of HIV infection has received considerable attention. Here, the authors discuss the importance of CD8⁺ T cells in HIV infection and suggest that efforts to develop vaccines that target these cells in conjunction with B cells should be renewed.

Immune subversion by primary tumours plays a key role in metastatic spread. This Review explores how primary tumours interfere with the crosstalk between immune cells to promote a chronic inflammatory yet immunosuppressed state that enables immune evasion and the formation of metastases.

In this Review, the authors encourage us to extend our concept of memory by considering the diverse cell types within a barrier tissue. They propose that any long-term resident or essential tissue cell type can store memory of previous immune events and cooperate in memory recall.

This Review considers how IgA operates alongside IgM, IgG and IgD to provide immune protection and promote homeostasis at mucosal tissue sites. The authors highlight how some of these neglected mucosal antibody isotypes may strengthen the communication between the mucosal and systemic immune compartments.

This Review describes the breakdown of ‘mucosal firewalls’ in patients with inflammatory bowel disease, involving immunological pathways that regulate microbial recognition and killing, immune responses to microorganisms and the reinforcement of the intestinal barrier.

Getting medicines to the right place at the right time is key to their success. Nanomedicines — drugs formulated in carrier materials that are smaller than 100 nm — show promise in enhancing tumour immunotherapy, owing to the ability to focus their action on target tissues and control their immunomodulatory properties, as reviewed here.

This Review discusses the various ways in which B cells, plasma cells and antibodies shape the immune response in cancer. B cells can have both protumour and antitumour roles, and the authors discuss the potential of targeting these cells for therapy.

Freeman and colleagues draw our attention to the existence of different forms of PDL1 — cell bound and various extracellular forms. Recent studies show that PDL1 on exosomes can inhibit antitumour immune responses and may be a useful biomarker for the management of cancer immunotherapy.

Studies of immune checkpoint therapy for cancer in 2019 uncovered critical insights into the differences between targeting CTLA4 versus PD1 and the role of particular T cell subsets in immune responses to cancer. Moreover, reverse translational studies are informing our understanding of resistance and response mechanisms in patients.