Masters of Immunology
Hye-Jung Kim and Harvey Cantor
Cancer Immunol Res February 1 2014 2 (2) 91-98; DOI:10.1158/2326-6066.CIR-13-0216
Beatty, Haas, and colleagues report antitumor activity in two patients treated with autologous T cells transfected with mRNA encoding a chimeric antigen receptor that recognizes mesothelin and contains the CD3-ζ and 4-1BB costimulatory domains (CARTmeso). The short-lived CARTmeso cells induced novel antiself antibodies and a broadly directed epitope spreading.
Arnold and colleagues identify the FAP+ CD45+ subpopulation of M2 macrophages as the major tumoral source of heme oxygenase-1 (HO-1), the inhibition of which alleviates tumoral immune suppression and arrests tumor growth. The authors suggest that targeting HO-1 may improve cancer immunotherapy.
Yuan, Zhou, and colleagues analyzed levels of serum VEGF in patients before and after ipilimumab therapy; they found that high pretreatment VEGF levels correlate with decreased overall survival. VEGF may serve as a biomarker for ipilimumab treatment.
Gulley and colleagues report immune responses from patients treated with PSA-TRICOM (a vaccinia prime/fowlpox boosts vaccine regimen with vectors expressing human PSA, B7.1, ICAM-1, and LFA-3), with 57% of 104 patients developing PSA-specific immune responses and 68% with antigen spreading.
Redmond and colleagues show that agonist ligation of OX40 while releasing the “brakes” on T cells via CTLA-4 blockade stimulates a unique CD4 and CD8 T-cell response that overcomes the limited efficacy of monotherapy and augments tumor immunotherapy.
Wang, Lo, and colleagues report the efficacy and safety of chimeric antigen receptor T cells specific for mouse fibroblast activation protein in inhibiting the growth of subcutaneously transplanted tumors when used alone and in combination with an antitumor vaccine.
Chen, Fu, and colleagues show that ICOS-mediated PI3K signaling is required for the expression of transcription factor T-bet, which regulates the Th1 antitumor response elicited by anti-CTLA-4 therapy, and suggest that targeting ICOS may improve Th1 antitumor responses.
Rughetti and colleagues show that unlike soluble glycoprotein antigens, MUC1 carried by microvesicles translocates from the endolysosomal/HLA-II to the HLA-I compartment, deglycosylates, and generates novel glycoepitopes for presentation by dendritic cells to MUC1-specific CD8+ T cells stimulating IFNγ responses.