Our data suggest that the angiogenic serum factors VEGF, bFGF, and IL-8 are useful predictive markers for overall and progression-free survival in melanoma patients.

Mitofusin 2 plays an unexpected role in maintaining the terpenoid biosynthesis pathway and is necessary for mitochondrial coenzyme Q biosynthesis.

TCF/Lef1 activity controls establishment of diverse stem and progenitor cell compartments in mouse epidermisThis work investigates cell fate and lineages of hair follicles and sebaceous glands (SG) in the mouse epidermis. The combination of transgenic models with complementary tracing techniques provides unequivocal evidence for a direct contribution of bulge stem cells to the SG units as well as stem cell niches within the isthmus region.

Adoptive T-cell transfer showed promising efficacy in recent trials raising interest in T cells with redirected specificity against tumors. T cells were engineered with a chimeric antigen receptor (CAR) with predefined binding and CD3ζ signaling to initiate T-cell activation. CD28 costimulation provided by a CD28-CD3ζ signaling CAR moreover improved T cell activation and persistence; however, it failed to meet the expectations with respect to mounting attacks against solid tumors infiltrated with regulatory T (Treg) cells. We revealed that a CD28 CAR-redirected T-cell attack is accompanied by higher numbers of Treg cells infiltrating the tumor and is less efficient against cancer cells in presence of Treg cells than a CD3ζ CAR T-cell attack. Deletion of the lck binding moiety in the CD28 CAR endodomain, however, improved redirected anti-tumor activity in presence of Treg cells without impairing interferon-γ (IFN-γ) secretion, proliferation, and cytolysis. CD28 modification abrogated interleukin-2 (IL-2) induction upon CAR engagement which in turn is no longer available to sustain Treg cell persistence. CARs with the modified CD28 endodomain thereby expedite the implementation of adoptive T-cell therapy in patients with a variety of cancer types that are heavily infiltrated by Treg cells.