Microbiota-shaped neutrophil senescence regulates sexual dimorphism in bladder cancer.

Sex disparities have been epidemiologically demonstrated in non-reproductive cancers, yet how the sex-specific intrinsic microbiome orchestrates the immune system to affect these disparities is unclear. Here we identify a subpopulation of RETNLGLCN2 senescence-like neutrophils (RLSNs) that preferentially accumulate in the male tumor microenvironment and exert a strong immunosuppressive effect to limit antitumor immunity, resulting in poor prognosis for patients with bladder cancer. This difference in enrichment of RLSNs between sexes can be attributed to intestinal bacterium Alistipes shahii, which preferentially populates in females rather than males.

Age-related decline in CD8 tissue resident memory T cells compromises antitumor immunity.

Aging compromises antitumor immunity, but the underlying mechanisms remain elusive. Here, we report that aging impairs the generation of CD8 tissue resident memory T (T) cells in nonlymphoid tissues in mice, thus compromising the antitumor activity of aged CD8 T cells, which we also observed in human lung adenocarcinoma. We further identified that the apoptosis regulator BFAR was highly enriched in aged CD8 T cells, in which BFAR suppressed cytokine-induced JAK2 signaling by activating JAK2 deubiquitination, thereby limiting downstream STAT1-mediated T reprogramming.

Chemoradiotherapy-induced ACKR2 tumor cells drive CD8 T cell senescence and cervical cancer recurrence.

Tumor recurrence after chemoradiotherapy is challenging to overcome, and approaches to predict the recurrence remain elusive. Here, human cervical cancer tissues before and after concurrent chemoradiotherapy (CCRT) analyzed by single-cell RNA sequencing reveal that CCRT specifically promotes CD8 T cell senescence, driven by atypical chemokine receptor 2 (ACKR2) CCRT-resistant tumor cells. Mechanistically, ACKR2 expression is increased in response to CCRT and is also upregulated through the ligation of CC chemokines that are produced by activated myeloid and T cells.

Pre-eclamptic foetal programming predisposes offspring to hepatic steatosis via DNA methylation.

Objectives: Gamete and embryo-foetal origins of adult diseases hypothesis proposes that adulthood chronic disorders are associated with adverse foetal and early life traits. Our study aimed to characterise developmental changes and underlying mechanisms of metabolic disorders in offspring of pre-eclampsia (PE) programmed pregnancy.

Methods: Nω-Nitro-l-arginine methyl ester hydrochloride (L-NAME) induced pre-eclampsia-like C57BL/6J mouse model was used.

BFAR coordinates TGFβ signaling to modulate Th9-mediated cancer immunotherapy.

TGFβ is essential for the generation of anti-tumor Th9 cells; on the other hand, it causes resistance against anti-tumor immunity. Despite recent progress, the underlying mechanism reconciling the double-edged effect of TGFβ signaling in Th9-mediated cancer immunotherapy remains elusive. Here, we find that TGFβ-induced down-regulation of bifunctional apoptosis regulator (BFAR) represents the key mechanism preventing the sustained activation of TGFβ signaling and thus impairing Th9 inducibility.