MiTEs are myeloid-targeted immunocytokine prodrugs that block TREM2+ tumor-associated macrophages while activating cytotoxic lymphocytes via TME-specific IL-2 activity, eliciting strong anti-tumor efficacy in preclinical models with minimal systemic toxicity.

Immunosuppressive monocyte-derived macrophages are key targets in cancer therapy; however, the mechanisms of their replenishment and functional plasticity remain elusive. In a recent issue of Nature, Hedge et al. challenge the conventional view that immunosuppressive macrophages are acquired exclusively through tumor microenvironment reprogramming; instead, their study demonstrates that the developmental fate of these macrophages is predisposed in the bone marrow.

Triple-negative breast cancer (TNBC) is characterized by high risks of relapse or metastatic disease. Mattavelli et al. identify a chemokine axis that recruits immunosuppressive monocytes to tumor-dra...

Bi et al. describe cell-type-specific transcriptional signatures of interferon (IFN) signaling in renal cell carcinoma (RCC) tumors and examine effects on immunotherapy outcomes. They find that myeloid IFNγ signaling, but not tumor IFNγ signaling, predicts poor outcomes in clinical trial cohorts, pointing to myeloid cells as mediators of IFN-driven immunotherapy resistance in RCC.

Tu et al. present a systematic analysis of the tumor microenvironment across 14,837 breast cancers, identifying distinct cellular patterns that predict disease-specific survival independently of genomic and intrinsic subtypes. Characterizing microenvironment composition may provide critical prognostic markers that can complement current molecular classification for treatment selection and preventing recurrence.

Triple-negative breast cancer (TNBC) is characterized by high risks of relapse or metastatic disease. Mattavelli et al. identify a chemokine axis that recruits immunosuppressive monocytes to tumor-draining lymph nodes. By co-targeting this recruitment, the TNBC response to immune checkpoint blockade is augmented and metastasis to the lung is reduced.

Lamkanfi, Shirasaki, Izawa and colleagues show that IL-1β release in human monocytes stimulated with lipopolysaccharide or carrying NLRP3 activatory mutations is mostly restricted to cells undergoing…

By sidestepping Cas9 immunogenicity, the StealTHY CRISPR platform enables immune-compatible in vivo genetic screens, directly translatable to humanized cancer models. Using this immune-stealth strategy allows for the discovery of metastatic drivers and reveals the AMH-AMHR2 axis as a clinically actionable pathway for dampening carcinoma metastasis.

Sanchez-Garcia et al. report that systemic hypoxia-induced epigenetic reprogramming of neutrophil progenitors in the bone marrow reduces their effector function to limit lung tissue damage.

Team says it has hit on an explanation for heartbreaking “lip outs”

Targeting FSP1 in lymph nodes has considerable potential for blocking melanoma progression.

This Perspective presents a framework of ‘structural immunity’ that positions immune cells as architects of tissue structure. Beyond their roles in antimicrobial defence, we posit that immune cells co...

Nature Metabolism, Published online: 20 October 2025; doi:10.1038/s42255-025-01398-4Cancer cells often increase their uptake of acetate for acetyl-coenzyme A biosynthesis, a mechanism that facilitates cancer metastasis. We found that, in hepatocellular carcinoma, cancer cells induce acetate secretion from tumour-associated macrophages, driven by a cell–cell metabolic interaction involving lactate, the lipid peroxidation–aldehyde dehydrogenase 2 pathway and acetate.

The developing field of immunometabolism showcases how molecular insights inform on cellular-level responses to both internal context and environmental stimuli. For our focus issue on innate immunity, we spoke with researchers about the new doors they see opening in this area, from molecular crosstalk to therapeutic potential.