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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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Our understanding of the origin, phenotype and function of epidermal Langerhans cells and langerin-expressing dendritic cells has expanded in recent years, details of which, as well as the challenges that remain, are discussed in this Review.

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.

Being a parent scientist can feel like a catch-22, feeling guilty for both the time spent away from the children and the time spent away from the bench. Embracing healthy boundaries can be liberating but will only go so far if childcare remains unaffordable.

Window-of-opportunity trials, during which patients receive short-duration pre-surgical therapies, provide a platform for understanding the therapies’ mechanisms of action, but will require a paradigm shift in trial design, specimen collection and analysis.

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.

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.

What is the role and value of consortium biology in immunology? Here, the participants of the Immunological Genome Project share their thoughts on the benefits and shortcomings of 'big science' and discuss how the immunology community can profit from engaging in this type of discovery-led research.

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 addition to cancer cell-intrinsic effects, tumour growth can be regulated by cellular and molecular cues from the local tissue environment. This Review discusses how differences in cellular components and composition between tissue sites may influence the antitumour immune response, with potential implications for the design of therapeutic strategies.

Cells of the mononuclear phagocyte system (MPS) are usually defined by particular functional or phenotypical characteristics. However, this has led to confusion in the field, as many of the criteria that are used to define a particular cell population may actually be shared with other cell types. In this Opinion article, the authors propose that a new nomenclature that is based on cell ontogeny could enable a more robust classification of MPS cells.

Our understanding of the ontogeny of monocytes and macrophages, as well as their maintenance in the steady state, has recently undergone a renaissance. Here, Ginhoux and Jung discuss the evidence that has changed our view of the relationship between monocytes and tissue macrophages during development and in the steady state.