B cell infiltration in high-grade serous ovarian cancer associates with favorable prognosis. Nathan et al. show that tumor-draining lymph nodes in patients lack active germinal center responses and instead harbor quiescent tumor-reactive memory B cells clonally linked to tumor B cells, highlighting lymph nodes as memory reservoirs supporting intra-tumoral immunity.
Altered astrocyte-microglia interactions have been implicated in the pathogenesis of Alzheimer’s disease, but the underpinning mechanisms remain unclear. Zhang and colleagues show that astrocytic PAD2-mediated citrullination of vimentin activates microglia, worsens Aβ accumulation, and exacerbates cognitive deficits. These findings highlight astrocyte-microglia crosstalk as a potential therapeutic target for Alzheimer’s disease.
Lobel, Fonseca-Pereira, et al. demonstrate that dietary sulfur amino acids (Saa) enhance anti-tumor immunity in colon cancer. A high-Saa diet expands the bacterium Mucispirillum schaedleri, which activates a natural killer T cell-dendritic cell axis to restrict tumor growth, illustrating how nutritional interventions can be leveraged for cancer immunotherapy.
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Systemic lupus erythematosus is characterized by autoantibodies against nuclear antigens. In this issue of Immunity, Al Souz et al. report that kidney damage in lupus nephritis is sustained by stem-like CD8+ T cells that migrate from lymphoid tissues and then, driven by CD4+ T cells and IL-15 and IL-21, differentiate into cytotoxic effectors within tissue and retain pathogenic function despite exhaustion markers.
Diet impacts gut microbes and, subsequently, host immunity, but our understanding of the mechanisms driving this axis remains incomplete. Hattori-Muroi, Maruta, Takahashi, et al. show that dietary soy promotes colonization of commensals that cooperatively induce Tfh cells and polyreactive IgA in Peyer’s patches. This polyreactive IgA maintains gut microbiota homeostasis and confers protection against Salmonella infection.
Preservation of host fitness is a common feature of longevity and immunity to infection. In this issue of Immunity, Triana-Martinez et al. reveal that p16High senescence-associated immune cells promote disease tolerance and healthy aging. Mechanistically, this is dependent on Toll-like receptor 7 (TLR7) and stimulator of interferon genes (STING) innate immune signaling controlling adenosine concentrations.
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Cholesterol metabolism is an essential component of all immune cells. Xu and colleagues review the immunological functions of cholesterol metabolites and proteins and discuss how distinct cholesterol metabolic programs fulfil the metabolic and signaling demands of different immune cells. How immune cholesterol metabolism contributes to major human diseases and relevant therapeutic strategies are also summarized and discussed.
Patients with psoriasis show a durable clinical response to the anti-IL-23 biologic, risankizumab, even after treatment cessation. Here, Jiang et al. generate a longitudinal single-cell and spatial transcriptomics atlas of patients pre- and post-treatment. They reveal reduced CD8+ tissue-resident memory T cell expansion, diminished inflammatory dendritic cells, and decreased APOE+/IL34+ fibroblasts associated with lasting amelioration of psoriatic inflammation.
Fibroblasts are highly attuned for immune crosstalk within lymphoid tissues. In this issue of Immunity, Alouche et al. provide insight into how fibroblast immunoregulatory phenotypes are acquired and maintained, revealing that Ccl19hi fibroblastic reticular cells require continuous signaling via Notch2. Dendritic cells produce Notch ligands to promote CCL19-rich stromal niches, which cluster CD8+ T cells centrally in lymph nodes.
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The presence of tertiary lymphoid structures (TLSs) associates with improved anti-tumor immunity, and as such, understanding why some tumors develop TLSs is of prime interest. In the current issue of Cancer Cell, Kirschstein et al. demonstrate that TGFβ-driven programming of myofibroblastic cancer-associated fibroblasts blocks reticular fibroblast differentiation and TLS formation in pancreatic cancer, a barrier reversible by TGFβR1 inhibition.
