Repurposing the yellow fever vaccine for intratumoral immunotherapy.

Live 17D is widely used as a prophylactic vaccine strain for yellow fever virus that induces potent neutralizing humoral and cellular immunity against the wild-type pathogen. 17D replicates and kills mouse and human tumor cell lines but not non-transformed human cells. Intratumoral injections with viable 17D markedly delay transplanted tumor progression in a CD8 T-cell-dependent manner.

For Whom the Cell Tolls? Intratumoral Treatment Links Innate and Adaptive Immunity.

Intratumoral immunotherapy can potentially modulate the tumor microenvironment (TME) and potentiate the effects of concomitant or sequential systemic immunotherapies. Intratumoral administration of different Toll-like receptor agonists, including TLR4, can potentiate these effects through innate and adaptive immunity connection.See related article by Bhatia et al.

Mitochondrial Morphological and Functional Reprogramming Following CD137 (4-1BB) Costimulation.

T and NK lymphocytes express CD137 (4-1BB), a costimulatory receptor of the TNFR family whose function is exploitable for cancer immunotherapy. Mitochondria regulate the function and survival of T lymphocytes. Herein, we show that CD137 costimulation provided by agonist mAb and CD137L (4-1BBL) induced mitochondria enlargement that resulted in enhanced mitochondrial mass and transmembrane potential in human and mouse CD8 T cells.

Lipid nanoparticles protect from edelfosine toxicity in vivo.

Edelfosine, an alkyl-lysophospholipid antitumor drug with severe side-effects, has previously been encapsulated into lipid nanoparticles (LN) with the purpose of improving their toxicity profile. LN are made of lipids recognized as safe by the Food and Drug Administration (FDA) and, therefore, these systems are generally considered as nontoxic vehicles. However, toxicity studies regarding the use of LN as vehicles for drug administration are limited.

Edelfosine lipid nanoparticles overcome multidrug resistance in K-562 leukemia cells by a caspase-independent mechanism.

The antitumor ether lipid edelfosine is the prototype of a novel generation of promising anticancer drugs that has been shown to be an effective antitumor agent in numerous malignancies. However, several cancer types display resistance to different antitumoral compounds due to multidrug resistance (MDR). Thus, MDR is a major drawback in anticancer therapy.

Efficacy of edelfosine lipid nanoparticles in breast cancer cells.

Breast cancer is a heterogeneous group of neoplasms predominantly originating in the terminal duct lobular units. It represents the leading cause of cancer death in women and the survival frequencies for patients at advanced stages of the disease remain low. New treatment options need to be researched to improve these rates.

Downregulation of FOXP1 is required during germinal center B-cell function.

B-cell maturation and germinal center (GC) formation are dependent on the interplay between BCL6 and other transcriptional regulators. FOXP1 is a transcription factor that regulates early B-cell development, but whether it plays a role in mature B cells is unknown. Analysis of human tonsillar B-cell subpopulations revealed that FOXP1 shows the opposite expression pattern to BCL6, suggesting that FOXP1 regulates the transition from resting follicular B cell to activated GC B cell.

LMO2 expression reflects the different stages of blast maturation and genetic features in B-cell acute lymphoblastic leukemia and predicts clinical outcome.

Background: LMO2 is highly expressed at the most immature stages of lymphopoiesis. In T-lymphocytes, aberrant LMO2 expression beyond those stages leads to T-cell acute lymphoblastic leukemia, while in B cells LMO2 is also expressed in germinal center lymphocytes and diffuse large B-cell lymphomas, where it predicts better clinical outcome. The implication of LMO2 in B-cell acute lymphoblastic leukemia must still be explored.