Tumor-Specific CD8 T Cells from the Bone Marrow Resist Exhaustion and Exhibit Increased Persistence in Tumor-Bearing Hosts as Compared to Tumor Infiltrating Lymphocytes.

Immunotherapy is now an integral aspect of cancer therapy. Strategies employing adoptive cell therapy (ACT) have seen the establishment of chimeric antigen receptor (CAR)-T cells using peripheral blood lymphocytes as well as tumor infiltrating lymphocytes (TILs) with significant clinical results. Despite these successes, the limitations of the current strategies are also emerging and novel approaches are needed.

RORγ Agonists Enhance the Sustained Antitumor Activity through Intrinsic Tc17 Cytotoxicity and Tc1 Recruitment.

Activation of RORγ with synthetic small-molecule agonists has been shown to enhance type 17 effector (CD4 Th17 and CD8 Tc17 cells) cell functions and decrease immunosuppressive mechanisms, leading to improved antitumor efficacy in adoptive cell transfer and syngeneic murine tumor models. However, whether Tc17 cells possess intrinsic cytotoxicity and the mechanism they use to lyse target cells is controversial. We report here that Tc17 cells were lytic effectors dependent on perforin and granzyme A.

Synthetic RORγ agonists regulate multiple pathways to enhance antitumor immunity.

RORγt is the key transcription factor controlling the development and function of CD4 Th17 and CD8 Tc17 cells. Across a range of human tumors, about 15% of the CD4 T cell fraction in tumor-infiltrating lymphocytes are RORγ+ cells. To evaluate the role of RORγ in antitumor immunity, we have identified synthetic, small molecule agonists that selectively activate RORγ to a greater extent than the endogenous agonist desmosterol.

Emergence of Klebsiella pneumoniae coproducing KPC-2 and 16S rRNA methylase ArmA in Poland.

A Klebsiella pneumoniae epidemic strain that coproduced carbapenemase KPC-2 (K. pneumoniae carbapenemase 2) and 16S rRNA methylase ArmA has emerged in Poland. Four nonduplicate isolates from patients in a hospital in Warsaw, Poland, were found to carry the bla(KPC-2) and armA genes on ca.

[Dissemination of the KPC carbapenemase producing Klebsiella pneumoniae in a hospital in Warsaw, Poland].

Within the last decade, human infections caused by enterobacteria which produce the Klebsiella pneumoniae carbapenemase (KPC) became a serious therapeutic and epidemiological problem worldwide. The KPC producing strains of K. pneumoniae broadly disseminated in the USA then spread to Europe.