Volume 24 Issue 2, February 2018

Two recent studies describe clinical successes for single-dose gene therapy in trials for two forms of hemophilia.

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.

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 recent study investigates the contribution of epigenomic plasticity to lung metastasis in osteosarcoma. Changes in the enhancer landscape were found to be nonrandom and driven by selective forces in the microenvironment.

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.

Complete vaccine-mediated immune control of highly pathogenic Mycobacterium tuberculosis is possible if immune effector responses can intercept the infection at its earliest stages.

Among many populations of blood cells, high dimensional analysis using mass cytometry reveals classical monocyte frequency as strong predictors of response to PD-1 blockade therapy of melanoma.

A recurrent ECSIT mutation in individuals with extranodal natural killer/T cell lymphoma induces NFκB in cancer cells, leading to macrophage activation, and associates with progression to fatal hemophagocytic syndrome. NFκB-targeting therapy produced stable remission in two patients.

Pier Paolo Pandolfi and colleagues report that the genetic background of tumors in mice recruits specific immune-cell subsets, suggesting that precision medicine should account for both the tumor drivers and the distinct immune-cell microenvironments that they elicit.

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.

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.

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.

The deubiquitinase CYLD regulates a TAK1–JNK pathway and can be targeted to ameliorate nonalcoholic steatohepatitis.

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.

Platelet activation after muscle trauma promotes extracellular trap release by macrophages and acute kidney injury.

A luteinizing hormone–releasing hormone antagonist, used clinically for sex-steroid inhibition, promotes quiescence of hematopoietic stem cells and thereby promotes hematopoietic recovery and survival of lethally irradiated mice.