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A recent study identifies an immune cell type known as classical monocytes in the peripheral blood as a potential biomarker for response to anti-PD-1 immune checkpoint therapy in metastatic melanoma.
Tailoring treatment to the individual patient has revolutionized cancer therapy, but personalized medicine has yet to make much headway in the treatment of cardiovascular disease. With emerging insight into disease mechanisms and new treatment options, the time is now ripe for the cardiovascular field to adopt a more personalized approach to therapy.
A recent study in mice dissects the mechanisms through which muscle damage leads to kidney dysfunction and identifies macrophage extracellular trap (MET) formation as a new pathogenic driver and potential therapeutic target.
In a recent study using cytomegalovirus (CMV)-vectored vaccines in rhesus macaques, prevention of tuberculosis in over 40% of vaccinated animals is shown and is attributed to reprogrammed innate immunity and CMV's maintenance of vaccine-elicited effector memory T cells.
A large proportion of basal cell carcinomas develop resistance independently of the canonical mutations in genes encoding hedgehog pathway components. An unbiased analysis investigating alternative pathways of resistance uncovers the role of cytoskeletal signaling in driving noncanonical activation of hedgehog signaling through nuclear translocation of SRF and MKL1. These results advance understanding of the mechanisms underlying drug resistance and provide new actionable insights for clinical translation.
Optimal T cell activation requires signaling through the T cell receptor (signal 1), a co-stimulatory receptor (signal 2) and a cytokine receptor (signal 3), yet most chimeric antigen receptors (CARs) lack a domain to transduce signal 3. Kagoya et al. now report their development of a new CAR that incorporates a JAK–STAT cytokine signaling domain and mediates potent antitumor effects.
A small-molecule antagonist of PPAR-γ expands human cord blood HSPCs via downregulation of fructose 1,6-bisphosphatase expression, thereby enhancing glycolysis.
A small molecule selectively targeting the cell-surface glutamine transporter ASCT2 disrupts glutamine signaling and metabolism. This compound displays low toxicity and strong antitumor activity in preclinical in vitro and in vivo models, thus holding promise as a treatment for glutamine-dependent tumors in a clinical setting.
Expression of AXL earmarks melanoma cells resistant to BRAF and MEK inhibitors that either pre-exist in treatment-naive tumors or emerge in response to therapy. The combination of an AXL-MMAE antibody-drug conjugate with BRAF and MEK inhibitors eliminates heterogeneous melanoma cell populations and prolongs survival in experimental in vivo models at tolerable toxicity. This approach is currently being tested in clinical trials and provides insights into the therapeutic targeting of intra-tumor heterogeneity.
Hyer et al. generate a potent and specific small-molecule inhibitor of the E1 ubiquitin-activating enzyme UBE1 that has antitumor activity in mice against a wide variety of tumor types.
Myeloid-derived suppressor cells are induced in newborn mice by breast-milk-derived lactoferrin and confer protection in a model of necrotizing enterocolitis. Their frequency and suppressive activity is decreased in very low-weight infants.
Complete vaccine-mediated immune control of highly pathogenic Mycobacterium tuberculosis is possible if immune effector responses can intercept the infection at its earliest stages.
Peter Scacheri and colleagues report that the activity of enhancer elements in metastatic osteosarcoma is distinct from that in primary tumors and plays a functional role in metastatic progression of osteosarcoma.