Cancer Immunol Res July 1 2015 3 (7) 703-703; DOI:10.1158/2326-6066.CIR-15-0128
Leo and colleagues compared CARD9-competent and CARD9-deficient APCmin mice and show that CARD9 reduces viability in male mice and promotes tumorigenesis specifically in the large intestine, with a correlative disruption of plasma cytokine expression and immune infiltration of the tumors.
Yu and colleagues show that the loss of SOCS3, a negative regulator of STAT3, in myeloid cells, leads to the development of MDSC and immunosuppressive activity within the tumor microenvironment via a G-CSF/STAT3 axis, and suggest targeting of SOCS3 in myeloid cells to regulate antitumor immunity.
Kao and colleagues performed a comprehensive analysis in a lung cancer mouse model and show that sequential chemoradiotherapy had an equivalent amount of antitumor activity compared with concurrent therapy, but the two regimens elicited differences in immune response biomarkers, including Tregs, microRNA-29c, CD28, and serum IFNγ.
Kloos and colleagues show that polysialic acid–specific retargeting of systemically administered oncolytic viruses leads to effective tumor infection, CD8 T-cell responses for mutated tumor neoepitope Gsta2-Y9H, and improved survival in an immunocompetent mouse model of disseminated lung cancer.
Schmittnaegel and colleagues describe the generation of a novel tumor-peptide-MHCI–antibody fusion protein that redirects a highly functional subset of CMV-specific T cells to eliminate tumor cells by engaging a naturally occurring T-cell population in humans that controls cytomegalovirus infection.
Gibson and colleagues show that outbred domestic cats develop mammary tumors similar to those in humans. Electrovaccination of heterologous or point-mutated feline HER2 DNA overcomes T-cell immune tolerance in 40% of healthy cats and induces antibodies with distinct specificity.
Hartlage, Liu, and colleagues show that vaccination of hu-PBL-SCID mice with EBV protein BZLF1-pulsed dendritic cells induced specific cellular immunity and prolonged survival from fatal EBV-driven lymphoproliferative disease, identifying BZLF1 as a prophylactic vaccine candidate for EBV-associated diseases.
Bardhan and colleagues show that short-chain fatty acid receptor GPR109A functions as a tumor suppressor that is silenced by DNA methylation in colon cancer, while host immune cytokine IFNγ upregulates GPR109A expression, via pSTAT1/p300 activation and H3K18 acetylation, to suppress tumor development.
Dennis and colleagues show that in the small intestine CD4+ T cells are the major sources of IL10, and ablation of IL10 in CD4+ T cells leads to loss of IFNγ-dependent immune surveillance, resulting in inefficient Th1 commitment and carcinoma transition by slowing polyp growth and enhancing invasiveness.
Wang and colleagues describe a new multichain, chimeric antigen receptor (CAR) that uses portions of KIR2DS2 to engage DAP12, mimicking natural NK- and T-cell signaling. This new CAR triggers potent T-cell antitumor responses in vivo due to improved retention of CAR surface expression and effector function.