In the Spotlight
Carl H. June
Cancer Immunol Res August 1 2016 4 (8) 643-643; DOI:10.1158/2326-6066.CIR-16-0132
Anti-CCR4 treatment of ATL destroys leukemic and normal Tregs, which can lead to autoimmunity. Only leukemic Tregs expressed CADM1, distinguishing the two populations. Treg depletion was associated with autoimmunity and Treg reemergence with relapse of ATL.
PD-1/CTLA-4 dual blockade has shown substantial promise against refractory tumors in some patients. Biomarkers were sought to identify patients early in treatment who are responding positively. Strong production of IFNγ shortly after treatment commenced significantly correlated with survival.
On-target/off-tumor effects can be problematic if the antigen target for CAR T-cell therapy is also expressed on normal tissue. An inducible CAR expression strategy was used that controlled CAR expression and shows promise in discriminating between tumor and B-cell expression of CD19.
On-target/off-tumor effects can be problematic if the antigen target for CAR T-cell therapy is also expressed on normal tissue. An inducible CAR expression strategy was used that controlled CAR expression and shows promise in discriminating between tumor and B-cell expression of CD19.
PD-1 ligand expression and T-cell infiltration may predict responsiveness to PD-1 pathway inhibitors. ACC tumors expressed PD-L2 and the Wnt and PI3K pathways but had little immune infiltration. Chemoradiotherapy promoted antitumor responses, suggesting potential synergies with PD-1 blockade.
HER2 is overexpressed in many breast tumors. A therapy was developed that targeted pIC (a TLR3 ligand) to HER2-positive tumors. Tumor growth was significantly inhibited, and antitumor immunity was activated via multiple signaling pathways.
Lenalidomide is a potential therapy for patients with CLL. It induces IL21 production by T cells while increasing IL21 receptors on CLL B cells, with concomitant cytotoxicity to CLL B cells, operating through multiple mechanisms.
The mechanisms underlying the costimulatory effects of TLR2 engagement on T cells are poorly understood. Costimulatory TLR1–TLR2 signaling in CD8+ T cells was found to be largely mediated by 4-1BB and contributes to mounting an antitumor immune response.