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  • Myeloid cells contribute to the immunosuppressive tumour microenvironment and can be responsible for resistance to cancer immunotherapy. Here, the authors describe the current therapies that aim to modulate the functional activities of myeloid cell populations, impacting their recruitment, survival and activity in the tumour microenvironment, acting at the level of cell surface receptors, signalling pathways, epigenetic machinery and metabolic regulators.

    • Sangeeta Goswami
    • Swetha Anandhan
    • Padmanee Sharma
    Review Article
  • In individuals with Down syndrome, immune dysregulation is partially caused by chromosome 21 trisomy. Here, we discuss how these immune differences may result in poorer COVID-19 outcomes, including diminished responses to vaccination and possibly elevated risk for long COVID.

    • Manini Majithia
    • Susan P. Ribeiro
  • In this Perspective, the authors reflect on the historical development of host-directed immunotherapeutic interventions for viral and bacterial infections, and then focus on how historical insights can be applied to current approaches to therapy of SARS-CoV-2 and Mycobacterium tuberculosis infections.

    • Robert S. Wallis
    • Anne O’Garra
    • Andreas Wack
  • The cytokine thymic stromal lymphopoietin (TSLP) has pleiotropic functions beyond allergic diseases and T helper 2-type immune responses. Here, the authors highlight the roles of TSLP — beneficial or deleterious — in infectious disease, chronic inflammatory disease and cancer by acting on many different cell types.

    • Risa Ebina-Shibuya
    • Warren J. Leonard
    Review Article
  • This Review explains how natural killer (NK) cells promote immunity to tumours. The authors cover the therapeutic approaches that are being developed to mobilize NK cells in patients with cancer, including NK cell activators, checkpoint blockade, cellular therapies, and bispecific and trispecific NK cell activating antibodies.

    • Natalie K. Wolf
    • Djem U. Kissiov
    • David H. Raulet
    Review Article
  • Among the multi-organ complications of Long COVID, those associated with cardiometabolic syndrome were some of the most prevalent in recent studies of population-scale data. Given the potential health and economic burdens, there is an urgent need to better define the inflammatory processes involved.

    • Justin J. Frere
    • Benjamin R. tenOever
  • Lymph node colonization by tumour cells promotes subsequent spread to distant tissues by inducing broad alterations in tumour immunity and generating tumour-specific immune tolerance.

    • Lucy Bird
    Research Highlight
  • Mast cells are complex immune cells with varied functions. This Perspective explores the divergent phenotypes and functions of mast cells resulting from both their hard-wired ‘nature’ defined by their ontogeny and the ‘nurture’ they receive within specialized tissue microenvironments.

    • Ashley L. St. John
    • Abhay P. S. Rathore
    • Florent Ginhoux
  • A preprint by Ho et al. investigates the role of decreased CD58 expression in cancer cell immune evasion, through both lack of T cell co-stimulation and increased T cell inhibition.

    • Max Quastel
    • Michael Dustin
    Journal Club
  • FlipFlop mice, in which the coreceptor proteins encoded by the Cd4 and Cd8 loci are reversed, shed light on the importance of T cell receptor signal length versus signal strength in determining helper versus cytotoxic T cell lineage fates.

    • Kirsty Minton
    Research Highlight
  • Patients with autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, type 1 diabetes and systemic lupus erythematosus, have distinct gut microbiota compositions compared to healthy controls. This Review explores how the gut microbiota influence autoimmune responses in extra-intestinal autoimmune diseases and discusses potential preventative and therapeutic strategies targeted at the microbiota–immune interface.

    • Eiji Miyauchi
    • Chikako Shimokawa
    • Hiroshi Ohno
    Review Article
  • Improving on current cancer immunotherapies will require engaging immune effectors beyond T cells alone. Predator–prey theory can reveal understudied and counterintuitive facets of antitumour immunity, inspiring new approaches to manipulate the tumour ecosystem in favour of cancer cell extinction.

    • Phineas T. Hamilton
    • Bradley R. Anholt
    • Brad H. Nelson
  • Epigenetic rewiring of bone marrow progenitor cells as a result of one inflammatory disease can enhance susceptibility to a distinct disease.

    • Yvonne Bordon
    Research Highlight