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A preprint by Cortez et al. explores how IL-25 produced in response to helminth infection in mice rewires intestinal ILC2s to retain a 'memory' of prior infection.

In non-small cell lung cancer, the presence of monocyte-derived macrophages inversely correlates with the presence of NK cells. Merad and colleagues propose that when monocytes phagocytose tumor debris they express TREM2, become pro-tumorigenic, and suppress NK cell recruitment and activation in tumors.

Response to anti-PD-1 in patients with hepatocellular carcinoma is associated with clonal expansion of intratumoral CXCL13⁺ CD4⁺ helper T cells and effector-like CD8⁺ T cells, and local dendritic cells enriched in expression of maturation and regulatory molecules help facilitate CD8⁺ T cell differentiation.

Antigen present and presented in the structures of the skin can result in immune responses that elicit tolerance, protective immunity or allergy, depending on the immunological context. Here the authors describe a key role for the hair follicle and CD11b⁺ dendritic cells in the priming of local antigenic tolerance.

To mature, dendritic cells collect and synthesize cholesterol to construct lipid nanodomains on their membranes. Obstructing this process impairs their ability to prime T cells.

In this Comment article, Florent Ginhoux, Martin Guilliams and Miriam Merad call for a revised nomenclature of the dendritic cell (DC) lineage to distinguish between DC subsets and DC states and resolve confusion in the light of single-cell transcriptional profiling results.

Early dissemination of cancer cells has been reported to occur in certain breast cancer models. Here the authors show that intra-epithelial macrophages in the early pre-cancer lesions drive early cancer cell dissemination through Wnt-1 secretion and that such events impact the later development of metastasis.

Treatment with ionizing radiation can lead to the accumulation of tumor-infiltrating T_reg cells. Merad and colleagues show that Langherans cells resist ionizing radiation via expression of p21 and potentiate the generation and accumulation of T_reg cells.

Single-cell transcriptomics studies on human and mouse non-small cell lung cancer and conditional knockout mouse models show that IL-4 from bone marrow basophils drives the development of granulocyte-monocyte progenitors to myeloid cells that suppress antitumour immunity.

Amit and colleagues report that the specific interaction of a CD4⁺PD-1⁺CXCL13⁺ T-cell subset with antigen-presenting cells reprograms the tumor microenvironment and response to immune checkpoint inhibitors in non-small cell lung cancer.

Multisystem inflammatory syndrome in children (MIS-C) onsets in COVID-19 patients with manifestations similar to Kawasaki disease (KD). Here the author probe the peripheral blood transcriptome of MIS-C patients to find signatures related to natural killer (NK) cell activation and CD8+ T cell exhaustion that are shared with KD patients.

The transcriptional regulation of commitment to the dendritic cell (DC) lineage and functional specialization of DCs in vivo is poorly understood. In this Resource, Merad and colleagues identify the lineage relationships among various tissue DC subsets.

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis involving evasion of immune control. Here, the authors perform a comprehensive analysis of single-cell multi-omic data revealing either a myeloid-enriched or adaptive-enriched tumour microenvironment, linked to distinct B and T cell clonal selection and differentiation, distinct overall survival, and potential therapeutic approaches.

Using multiple datasets from real-world evidence and completed trials, a machine learning model using routine blood and clinical data is shown to be predictive of patient response to immune checkpoint inhibitor therapy, across cancer types and outperforming standard biomarkers.

Single-cell RNA sequencing and imaging of macrophages in human non-small cell lung cancer and in a mouse model of lung adenocarcinoma show that tissue-resident macrophages have a key role in early tumour progression.

Senescence of hematopoietic progenitor cells, enforced by the BRAF^V600E mutation, underlies the development of Langerhans cell histiocytosis and could be a new target for drug development and therapy of this disease in patients.

Immunoengineering-based cancer therapies have huge potential. Here the authors report on the lipid nanoparticle delivery, to cancer cells, of self-amplifying RNA encoding SARS-CoV-2 spike epitope-loaded MHC I molecules to take advantage of anti-SARS-CoV-2 immunity from a vaccinated population to treat cancer.

A preprint by Baer et al. looks at the role of pancreas tissue-resident macrophages in pancreatic tissue injury and fibrosis during pancreatitis and pancreatic ductal adenocarcinoma.

In situ vaccine recruits and activates cross-presenting dendritic cells and augments PD1 blockade efficacy in patients with indolent non-Hodgkin’s lymphoma.

Activation of a cellular stress response and the transcription factor XBP1 in dendritic cells has now been shown to limit the cells' ability to stimulate antitumour immune responses in a mouse model of ovarian cancer.

Two papers in this issue report the isolation and characterization of a common clonal bone marrow precursor of plasmacytoid and conventional dendritic cells.

Chow et al. report a crucial role for macrophages in erythroblast development in mice. Under conditions that induce new red blood cell formation, macrophage depletion impaired red blood cell recovery. Conversely, macrophage depletion normalized red blood cell counts in a mouse model of polycythemia vera, pointing to a potential new therapeutic strategy for this disease. Findings similar to these are reported in an accompanying paper by Ramos et al.

It is increasingly obvious that individuals are experiencing post-COVID-19 syndromes, or ‘long-haul COVID’. Here, Merad and Mehandru eview currently available knowledge of the underlying pathophysiological mechanisms of these sequelae, elaborating on persistent inflammation, induced autoimmunity and putative viral reservoirs.

This Progress article from Merad and Martin examines our current understanding of the excessive inflammatory responses seen in patients with severe COVID-19. The authors focus on the emerging pathological roles of monocytes and macrophages and discuss the inflammatory pathways that are currently being targeted in the clinic.

In this Comment article, organizers of the International School of Immunotherapy (Immunoschool) reflect on the experience gained from the past ten years in using online technologies for global and inclusive immunology education.

Transcriptomic analyses of acute phase whole blood from a large cohort of patients with COVID-19 identify molecular determinants of post-infection long-term sequelae.

This Comment article from the Precision Immunology Institute at the Icahn School of Medicine (PrIISM), New York, describes their efforts to provide critical reviews of COVID-19 articles posted daily on the preprint servers bioRxiv and medRxiv.

Immunologists are making good progress in unravelling the intricacies of the mononuclear phagocyte system, and this is largely due to recent technological advances. This article describes the current tools that exist for studying the origins and functions of mononuclear phagocytes and discusses the future technologies that will enable further progress in the field.

Macrophages can differentiate to perform homeostatic tissue-specific functions. Here the authors show that RXR signalling is critical for large peritoneal macrophage (LPM) expansion during neonatal life and LPM lipid metabolism and survival during adult homeostasis, and that ovarian cancer growth relies on RXR-dependent LPMs. 

After taking up tumour-associated antigens, dendritic cells in mouse and human tumours upregulate a regulatory gene program that limits dendritic cell immunostimulatory function, and modulating this program can rescue antitumor immunity in mice.

A preprint by Gschwend et al. describes the intercellular crosstalk between alveolar type 2 epithelial cells and basophils via GM-CSF that directs the development and maintenance of alveolar macrophages.

A preprint by Mayer et al. reveals the role played by environmental IL-13 in shaping the balance of type 2 dendritic cell molecular composition in the dermis.

Nature Immunology’s 20^th anniversary is a good opportunity to reminisce about the ImmGen collective endeavor — its goals, successes and horror stories — and the group’s exploration of various modes of scientific publishing.

Macrophages populate the body's tissues and organs, where they become highly specialized to preserve organ integrity in the event of microbial invasion or injury. A dynamic crosstalk between the macrophages and their surrounding tissue cells is crucial to ensuring this homeostatic function. This Review highlights the key molecules and mechanisms involved in macrophage–tissue interactions.

Dendritic cells (DCs) shape the adaptive immune response to peripheral tissue antigens and, as such, are crucial for mounting an effective antitumour immune response in cancer. This Review outlines the molecular basis of DC maturation, highlights the mechanisms through which cancer impairs DC maturation and considers the potential for DC-focused cancer immunotherapeutics.

Filipescu et al. report that macroH2A deficiency in cancer-associated fibroblasts leads to altered chromatin looping and elevated inflammatory gene expression, thereby affecting immune cell function and limiting the anti-tumour response in melanoma.