Several recent reports have demonstrated that B cell-targeting chimeric antigen receptor (CAR) T cells offer a viable treatment option for patients with autoantibody-mediated autoimmune diseases. To present additional data on this therapy and discuss strategies for more efficient clinical translation, leading experts in CAR T cell therapy for autoimmunity from various countries, including China, Germany

The role of type I interferon (IFN-I) in systemic lupus erythematosus (SLE) is well documented, but the role of interleukin (IL)-1β remains elusive. In this issue of Immunity, Caielli et al. identified an SLE monocyte population coproducing IL-1β and IFN-I and described how mitochondrial nucleic-acid-containing RBCs engage cGAS/STING, RIG-I, MDA5, and NLRP3 for unconventional IL-1β release.

Tissue-resident memory T (TRM) cells adapt to diverse environments, providing local long-term protection. In this issue of Immunity, Obers et al. and Raynor et al. demonstrate how diet, commensals, and host factors determine TRM cell development, maintenance, and function across tissues.

The mechanisms by which oncogenic mutations and anatomical locations work together to influence the immune environment within tumors are not well understood. In this issue of Immunity, Ross et al. show that H3.3K27M diffuse midline gliomas (DMGs) are enriched with disease-associated myeloid cells (DAMs). Myeloid-targeted strategies reprogram DAMs to a homeostatic state, reduce myeloid infiltration

Insufficient influx of T cells into the tumor microenvironment, including brain metastasis, dramatically limits efficacy of conventional immunotherapy. In this issue of Immunity, Messmer et al. interrogate spatiotemporal dependencies of melanoma brain metastasis T cell infiltration by intravital microscopy. They find that T cells enter these brain tumors through peritumoral venous vessels and can be

Resistance to tyrosine kinase inhibitors (TKIs) in lung cancer brain metastasis (LCBM) remains a clinical challenge. Recently in Cancer Cell, Fu et al. reveal how TKIs reshape the immune microenvironment of LCBM and propose CTLA4 blockade as a promising strategy to overcome resistance.

The immune system recognizes a multitude of innocuous antigens from food and intestinal commensal microbes toward which it orchestrates appropriate, non-inflammatory responses. This process requires antigen-presenting cells (APCs) that induce T cells with either regulatory or effector functions. Compromised APC function disrupts the T cell balance, leading to inflammation and dysbiosis. Although their

The meningeal lymphatics system plays diverse roles in facilitating neuroimmune function at brain borders, yet its specific contribution toward glial function and homeostasis is not known. In this issue of Immunity, Das Neves et al. (2024) describe a novel role for the meningeal lymphatics in maintaining oligodendrocyte survival and myelination.

Understanding the nature of human autoantigen-specific CD4+ T cells is limited by the difficulty of characterizing these cells ex vivo. In this issue of Immunity, Saggau et al. use ARTE technology to profile CD4+ T cells specific to disease-relevant autoantigens and find that such cells develop an exhausted phenotype that includes FOXP3 expression and persist for extended periods of time.

Understanding the factors that lead to the therapeutic success of adoptive cell therapies using tumor-infiltrating lymphocytes (TIL-ACT) will improve current treatment protocols. In this issue of Immunity, Chiffelle et al. comprehensively compare the dynamics of CD8+ T cell clonotypes during the course of ACT between responding and non-responding patients.

It’s crucial for skin to establish efficient defense strategies. Liu et al. reveal that the transcription factor ZNF750 recruits the histone demethylase KDM1A to silence pattern recognition receptors in the outer epidermis, making their expression limited to deeper, undifferentiated keratinocytes to address threats penetrating the skin.

PD-1 blockade partially reverses T cell exhaustion in cancer patients, but broad responses are still limited. Three studies recently published in Cell illuminate how abrogating LAG-3 and PD-1 synergize to further push effector T cell functionality via distinct molecular mechanisms.

Insight into how the immune system recognizes and responds to pathogens had led to landmark advances in biology and medicine in the last decades. This year’s Albert Lasker Award for Basic Medical Research honors Zhijian “James” Chen for the discovery of cGAS, the enzyme that senses foreign and “pathogenic” self-DNA—self-DNA aberrantly located in intracellular compartments. The definition of the cGAS-STING

The immune system has a vital, albeit complex, relationship with the microbes residing within us, one that we are only beginning to understand. We asked investigators what they felt were the fundamental challenges we currently face in unraveling the impacts of microbes and their metabolites on host immunity and to discuss key opportunities toward achieving future insights and innovation.

Our brain is not an immune-privileged island isolated from peripheries, but how non-neuronal brain cells interact with the peripheral system is not well understood. Wei et al. report that microglia in the hypothalamic paraventricular nucleus (PVN) with unique vasculature can detect ATP derived from hemodynamic disturbance. These microglia in the PVN regulate the response to hypertension via ATP-P2Y12-C/EBPβ

Intestinal macrophages play a key role in regulating immune tolerance in the gut. In this issue of Immunity, Mertens et al. uncover a mechanism for the establishment of memory in macrophage tolerance in the gut involving a bistable metabolic switch in macrophages and an intercellular positive feedback between macrophages and intestinal epithelial cells (IECs).

Aging leads to alterations that precipitate or aggravate several diseases that occur across our lifespan. In the CNS, aging affects the capacity to maintain and repair the myelin sheaths that protect axons and facilitate neuronal signaling. Tiwari et al. report aging-associated transcriptional responses in microglia after demyelination, which could be reversed by epigenetic remodeling after BCG vaccination

Tissue-resident memory CD8+ T cells serve as a first-line defense against many pathogens. In this issue of Immunity, Buquicchio et al. unveil the epigenomic landscapes of virus-specific CD8+ T cell subsets, highlighting common and organ-specific regulators driving their differentiation.

Chronic inflammation is considered a hallmark of aging. In a recent issue of Nature, Widjaja et al. examined genetic and pharmacologic inhibition of interleukin (IL)-11 on aging pathology and found that inhibiting IL-11 signaling increases lifespan and healthspan in mice.

Despite decades of antibody research, it remains challenging to predict the specificity of an antibody solely based on its sequence. Two major obstacles are the lack of appropriate models and the inaccessibility of datasets for model training. In this study, we curated >5,000 influenza hemagglutinin (HA) antibodies by mining research publications and patents, which revealed many distinct sequence features

The intestinal microbiota determines immune responses against extraintestinal antigens, including tumor-associated antigens. Indeed, depletion or gross perturbation of the microbiota undermines the efficacy of cancer immunotherapy, thereby compromising the clinical outcome of cancer patients. In this review, we discuss the long-distance effects of the gut microbiota and the mechanisms governing antitumor

The interferon-stimulated gene OAS1 has well-defined antiviral properties. In two recent issues of Immunity, Harioudh et al. describe a non-canonical function of OAS1 that selectively protects the translation of proteins involved in defense against viral or bacterial infections.

Diversity is a key feature of B cell biology—from BCR rearrangement to the heterogeneity of memory B cells. In this issue of Immunity, Wang et al. show that the zinc-finger protein ZFP318 supports mitochondrial health in certain memory B cells, thereby facilitating potent recall upon rechallenge.

Understanding determinants of immune response variation is central to developing treatment options. Even et al. show that naive CD4+ T cell transcriptional heterogeneity is altered by helminth infection leading to impaired immune responses independent of commensals.

The immune system is imprinted by gut microbes in early life. In this issue of Immunity, Perdijk et al. show that dysregulation of airway epithelial function by neonatal antibiotic treatment can be reversed by supplementation with a depleted microbial metabolite.

Response to immune checkpoint blockade is increased in obesity-related cancers, but the mechanisms remain unclear. In a recent issue of Nature, Bader et al. report that obesity in mice induces macrophage PD-1 upregulation to promote tumor growth while potentiating immunotherapy responses.