What We're Reading
Cancer Immunol Res January 1 2017 5 (1) 1-1;
Low oxygen levels in tumors can act as a barrier to effective antitumor immunity. Mitigation of tumor hypoxia using a commonly prescribed type II diabetes drug, metformin, resulted in significant synergy with PD-1 blockade immunotherapy.
Outcomes for metastatic melanoma patients treated with checkpoint blockade were poor when circulating Ang-2 was high. Ang-2 promoted recruitment of tumor macrophages and upregulated PD-L1, making it a predictive and/or prognostic biomarker and potential target to combine with checkpoint blockade.
Murine syngeneic tumor models are used to study responses to antitumor immunotherapies. To rationalize model selection, the underlying genetic and immunologic biology of the models was analyzed, allowing parallels to be drawn between models and human disease phenotypes.
The proteasome inhibitor bortezomib can synergize with other chemotherapies to kill nasopharyngeal carcinoma cells. Bortezomib released the immune suppression imposed by IFNγ-induced IDO (indoleamine 2,3-dioxygenase) through inhibition of NF-κB translocation, IRF-1 production, and STAT1 signaling.
Broad JAK inhibitors can improve graft-versus-host disease caused by stem cell transplants, but they reduce NK-cell numbers and activity. Selective inhibitors of JAK2, in concert with moDCs or Langerhans cells, preserve STAT5 signaling and NK-cell proliferation and function.
The source and role of IL4 in tumors is not clear. T follicular helper cells in the tumor-draining lymph nodes produced most of the IL4, which profoundly influenced the tumor microenvironment, enhancing M2-macrophage polarization and suppressing antitumor immunity.
Previous work on peptide vaccines has focused primarily on boosting either antibody or CTL responses. Here, a vaccine strategy was optimized that elicited strong and effective CD4 T-cell responses with therapeutic antitumor effects in a murine melanoma model.
This is a reanalysis of data described in Snyder et al., N Eng J Med 2014;371:2189–99, that also provides an open-source tool for comparing epitopes. No predictor of response to anti–CTLA-4 therapy was more accurate than mutation burden.