Androgen and Estrogen Receptor Status in Breast Cancer
Elebro et al. Page 3640
In this prospective, population-based epidemiological cohort study of 1,026 patients with primary invasive breast cancer, a significantly differential prognostic role of the androgen receptor (AR) tumor expression in patients with estrogen receptor alpha (ER)-positive and ER-negative tumors was demonstrated. Furthermore, AR-negativity was predictive of early treatment failure to aromatase inhibitors, but not to tamoxifen, among chemonaïve patients aged 50 or older with ER-positive tumors. The results warrant confirmation in an independent study, preferably in a randomized trial. In conclusion, AR tumor assessment may be useful in the clinical setting for improved tailoring of breast cancer treatment.
Antigen Spread after Treatment with Sipuleucel-T
GuhaThakurta et al. Page 3619
Antigen spread, an adaptive immune response to nontargeted tumor antigens following treatment with an antigen-specific immunotherapy may indicate tumor cell destruction and subsequent recognition of additional antigens. Using samples from a phase 3 clinical trial, GuhaThakurta and colleagues showed that antigen spread occurs within weeks of administration of sipuleucel-T, a cellular immunotherapy for prostate cancer directed against prostatic acid phosphatase. Most significantly, antigen spread was found to correlate with overall survival. These results suggest that antigen spread may serve as a posttreatment biomarker for the efficacy of immunotherapy, a finding with broad implications for the field of tumor immunology.
High-Dose Radiation Transforms Tumor Microenvironment
Filatenkov et al. Page 3727
Filatenkov and colleagues found that the high-dose radiation transformed the immunosuppressive tumor microenvironment by inducing an intense CD8+ T cell tumor infiltrate, and a loss of myeloid derived suppressor cells (MDSCs). The change was dependent on antigen cross-presenting CD8+ dendritic cells, secretion of IFN-γ, and CD4+T cells expressing CD40L. Antitumor CD8+ T cells entered tumors shortly after radiotherapy, reversed MDSC infiltration, and mediated durable remissions in an IFN-γ dependent manner. Interestingly, extended fractionated radiation regimen did not result in robust CD8+ T-cell infiltration.
Targeting STAT3 in MDSCs from Prostate Cancer Patients
Hossain et al. Page 3771
Prostate cancers develop immunosuppressive microenvironment resisting current treatments and the emerging immunotherapies. Hossain and colleagues identified a population of Lin−CD15HICD33LO granulocytic MDSCs (G-MDSCs) accumulating in patients during prostate cancer progression. The G-MDSCs secreted large amounts of Arginase 1, thereby suppressing T cells' proliferation and activity. The MDSC functions were under control of the STAT3 transcription factor and a central immune checkpoint regulator. To functionally eliminate prostate cancer-associated G-MDSC, the authors successfully employed an siRNA-based approach to silence STAT3 specifically in TLR9-expressing G-MDSCs. These findings underscore the potential of oligonucleotide-based therapeutics to alleviate immunosuppressive signaling in advanced prostate cancers.