Prolonged inhibition of intratumoral mast cells enhances efficacy of low-dose antiangiogenic therapy.

Low-dose antiangiogenic therapies have demonstrated the ability to enhance normalization of tumor vessels, consequently improving hypoxia levels, drug delivery, and promoting anticancer immune responses. Mast cells have been identified as contributors to resistance against antiangiogenic therapy and facilitators of abnormal neoangiogenesis. In this study, we demonstrate that by simultaneously targeting intratumoral mast cells with Imatinib and administering low-dose anti-VEGFR2 therapy, antitumor efficacy can be enhanced in preclinical models.

Regulation of bone homeostasis by MERTK and TYRO3.

The fine equilibrium of bone homeostasis is maintained by bone-forming osteoblasts and bone-resorbing osteoclasts. Here, we show that TAM receptors MERTK and TYRO3 exert reciprocal effects in osteoblast biology: Osteoblast-targeted deletion of MERTK promotes increased bone mass in healthy mice and mice with cancer-induced bone loss, whereas knockout of TYRO3 in osteoblasts shows the opposite phenotype. Functionally, the interaction of MERTK with its ligand PROS1 negatively regulates osteoblast differentiation via inducing the VAV2-RHOA-ROCK axis leading to increased cell contractility and motility while TYRO3 antagonizes this effect.

AXL Inhibition Represents a Novel Therapeutic Approach in Negative Myeloproliferative Neoplasms.

negative myeloproliferative neoplasms (MPNs) consist of essential thrombocythemia, polycythemia vera, and myelofibrosis. The majority of patients harbor the -activating mutation V617F. JAK2 inhibitors were shown to reduce symptom burden and splenomegaly in MPN patients.

Influence of Androgens on Immunity to Self and Foreign: Effects on Immunity and Cancer.

It is well-known that sex hormones can directly and indirectly influence immune cell function. Different studies support a suppressive role of androgens on different components of the immune system by decreasing antibody production, T cell proliferation, NK cytotoxicity, and stimulating the production of anti-inflammatory cytokines. Androgen receptors have also been detected in many different cells of hematopoietic origin leading to direct effects of their ligands on the development and function of the immune system.

Sexual dimorphism in solid and hematological malignancies.

Cancer represents a leading cause of death with continuously increasing incidence worldwide. Many solid cancer types in non-reproductive organs are significantly more frequent and deadly in males compared to females. This sex-biased difference is also present in hematologic malignancies.