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Forkhead transcription factor FoxF2 plays a crucial role in the development of organs derived from primitive gut. Here the authors show that reduction of Foxf2 expression in stromal cells is associated with high grade prostate cancer and that increasing prostatic stromal Foxf2 sensitizes prostate cancer to immune checkpoint blockade.

Objective: Osteomyelitis of the hand in adults often requires debridement of necrotic tissue and antibiotics targeted at organisms isolated from bone samples. This study aims to review organisms associated with hand osteomyelitis to inform clinical decision making. Methods: A retrospective review of the organisms isolated from 210 patients with osteomyelitis of the phalanges and metacarpals of the hand in a major trauma centre was performed over twelve years. Results: Microbiological cultures were performed for 195 patients including 122 with positive bone cultures. Staphylococcus aureus was identified in 104 patients (50%), with coagulase negative staphylococci in 57 (27%) and Enterobacterales in 53 (25%). Eighty-eight were polymicrobial infections (42%). Arterial calcification was associated with polymicrobial infections, Enterobacterales and enterococci. Multi-drug resistant organisms occurred in 13 patients and were more frequently Enterobacterales than staphylococci or enterococci. Conclusions: The high incidence of polymicrobial infections and coagulase negative staphylococci in this series suggests that for suspected cases, early microbiological and histopathological confirmation, ideally via bone biopsy, is optimal for osteomyelitis of the hand.Level of evidence: IV.

The priming of immune T cells by their interaction with dendritic cells (DCs) in lymph nodes (LN), one of the early events in productive adaptive immune responses, occurs on a scaffold of lymphoid stromal cells, which have largely been seen as support cells or sources of chemokines and homeostatic growth factors. Here we show that murine fibroblastic reticular cells (FRCs), isolated from LN of B6 mice, play a more direct role in the immune response by sensing and modulating T cell activation through their upregulation of inducible nitric oxide synthase (iNOS) in response to early T cell IFNγ production. Stromal iNOS, which only functions in very close proximity, attenuates responses to inflammatory DC immunization but not to other priming regimens and preferentially affects Th1 cells rather than Th2. The resultant nitric oxide production does not affect T cell-DC coupling or initial calcium signaling, but restricts homotypic T cell clustering, cell cycle progression, and proliferation. Stromal feedback inhibition thus provides basal attenuation of T cell responses, particularly those characterized by strong local inflammatory cues.