Masters of Immunology
Eva Klein, Noemi Nagy and Eahsan Rasul
Cancer Immunol Res February 1 2015 3 (2) 97-102; DOI:10.1158/2326-6066.CIR-14-0238
Rodić and colleagues analyzed archival melanocytic lesions and cultured melanomas and found no correlation between melanocyte PD-L1 expression and BRAF V600E mutation, indicating that distinct biomarkers should be used to select patients for BRAF inhibitor and PD-1/PD-L1 checkpoint blockade therapies.
Berrien-Elliott and colleagues report that combination checkpoint blockade induced expression of T-bet and Eomes but only T-bet was required to restore CD8+ antitumor effector function, leading to a >95% cure rate in leukemia-bearing mice given this immunotherapy regimen.
Hudecek, Sommermeyer, and colleagues show that modifications of the length and composition of the extracellular spacer of a chimeric antigen receptor (CAR) that abrogate its binding to Fc receptors can prevent off-target activation of CAR T cells and enhance their antitumor efficacy.
Shen, Sundstedt, and colleagues show in murine models that tasquinimod enhanced the antitumor effects of SurVaxM tumor vaccine for prostate cancer and of 5T4Fab-SEA tumor-targeted superantigen for melanoma by inhibiting the accumulation and function of tumor-infiltrating suppressive myeloid cells.
Chen, Lee, and colleagues compared the antitumor activity of anti-PD-1 in combination with anti-4-1BB versus with anti-LAG-3 and showed in syngeneic, poorly immunogenic mouse tumor models that the combination with anti-4-1BB elicited superior and well-tolerated tumor inhibition that did not require vaccine.
Théate, van Baren, and colleagues used a highly specific antibody to characterize IDO1 expression in a large series of healthy and tumoral human tissues to facilitate the selection of appropriate tumor types for pharmacologic IDO1 inhibition and to anticipate possible side effects of this treatment.
Liu and colleagues show that afucosylated antibodies potentiate ADCC by increasing the cytotoxic rate and number of NK cells capable of killing multiple targets, which results from increased affinity between antibodies and FcγRIIIa to enhance activation of signaling molecules that promote cytoskeletal rearrangement and degranulation.
Rahbar and colleagues show that B7-H4 promotes antitumor immunity against mouse mammary cancer and insulinomas and that its expression levels correlate with those of MHC class I in mouse and human tumors; high B7-H4 expression is associated with improved recurrence-free survival in breast cancer patients.
Zhang, Tang, Zhang, and colleagues report that wide-spectrum antitumor immunity from vaccination with tumor microparticles (T-MP) or T-MP–loaded dendritic cells (DC) is mediated by the cGAS/STING DNA-sensing innate immune pathway and production of type I IFN, which promotes DC maturation and tumor-antigen presentation.
Berger and colleagues adoptively transferred autologous ROR1 chimeric antigen receptor-modified T (CAR-T) cells into nonhuman primates to demonstrate the safety, persistence, and function of ROR1 CAR-T cells in vivo, and the utility of the model for preclinical testing of novel CARs.