Can't drop the MIC(A/B): Preventing stress-ligand shedding to enhance pan-cancer targeting.

Chimeric antigen receptor (CAR)-based cellular therapies have achieved remarkable success against hematologic malignancies, but their application against solid tumors remains challenging. In this issue, Goulding et al. describe a unique CAR natural killer (NK) cell platform with pan-cancer activity via preservation and recognition of stress ligands on tumor cell membranes.

HA and M2 sequences alter the replication of 2013-16 H1 live attenuated influenza vaccine infection in human nasal epithelial cell cultures.

From 2013 to 2016, the H1N1 component of live, attenuated influenza vaccine (LAIV) performed very poorly in contrast to the inactivated influenza vaccine. We utilized a primary, differentiated human nasal epithelial cell (hNEC) culture system to assess the replication differences between isogenic LAIVs containing the HA segment from either A/Bolivia/559/2013 (rBol), which showed poor vaccine efficacy, and A/Slovenia/2903/2015 (rSlov), which had reasonable vaccine efficacy. There were minimal differences in infectious virus production in Madin-Darby Canine Kidney (MDCK) cells, but the rSlov LAIV showed markedly improved replication in hNEC cultures at both 32 °C and 37 °C, demonstrating that the HA segment alone could impact LAIV replication in physiologically relevant systems.

Natural killer cell immunosuppressive function requires CXCR3-dependent redistribution within lymphoid tissues.

NK cell suppression of T cells is a key determinant of viral pathogenesis and vaccine efficacy. This process involves perforin-dependent elimination of activated CD4+ T cells during the first 3 days of infection. Although this mechanism requires cell-cell contact, NK cells and T cells typically reside in different compartments of lymphoid tissues at steady state.

Targeting natural killer cells to enhance vaccine responses.

Vaccination serves as a cornerstone of global health. Successful prevention of infection or disease by vaccines is achieved through elicitation of pathogen-specific antibodies and long-lived memory T cells. However, several microbial threats to human health have proven refractory to past vaccine efforts.