Masters of Immunology
The Carcinoma-Associated Fibroblast Expressing Fibroblast Activation Protein and Escape from Immune Surveillance
Douglas T. Fearon
Cancer Immunol Res March 1 2014 2 (3) 187-193; DOI:10.1158/2326-6066.CIR-14-0002
Using cobra venom factor to induce transient C3 molecule exhaustion in a mouse model of melanoma, Janelle and colleagues show that the antitumor immune response is NK dependent, uncovering a link between complement proteins and NK cells in tumor development.
Alvarez Arias, Kim, and colleagues show that disruption of CD8+ Tregs binding to Qa-1+ T follicular helper cells (TFH) improves tumor vaccination-elicited immunity, a robust autoimmune antitumor response driven by enhanced TFH activity and a strong antibody response.
Zhou and colleagues identify a mechanism by which immune responses are primed against a developing tumor: Disruption of the HSP-CD91 pathway abrogates cross-presentation of tumor-derived antigenic peptides and prevents antitumor immunity that characterizes tumor immunosurveillance.
Chowdhury and colleagues use whole blood samples in ex vivo assays to show that ChiLob 7/4 induces a pattern of DC activation and cytokine secretion matching the in vivo responses, providing a strategy to predict dosages and cytokine release syndromes.
Chavan and colleagues analyzed peripheral blood monocytic cells from 18 patients with untreated stage IV melanomas; they found a decrease in the frequency of circulating myeloid dendritic cells and classical CD14+ CD16− monocytes, and the latter also have decreased functional capacity.
Ochi and colleagues engineered T cells to express chimeric CD16 V158-CD3ζ receptors that mediate antibody-dependent tumoricidal activity; upon stimulation these T cells proliferate and differentiate into effector memory T cells, which could combine with and enhance clinical responses by anticancer monoclonal antibodies.
Iheagwara and colleagues used a mouse model of influenza virus infection to validate a new cancer immunosurveillance hypothesis and show that viral infections elicit immunity against antigens abnormally expressed in infected cells and cancer cells that can provide effective anticancer control.
Hayes and colleagues report that polyamine elevation in cancer contributes significantly to tumor immunosuppression; they developed a novel polyamine-depletion strategy combining inhibitors of the polyamine transport system and ornithine decarboxylase to prevent tumor immune escape and promote antitumor immunity.