In the Spotlight
Cancer Immunol Res June 1 2016 4 (6) 473-473; DOI:10.1158/2326-6066.CIR-16-0089
It has become crucial to understand immunotherapy-induced changes to the immune system. Mass cytometry allowed the in-depth monitoring of multiple immune subsets during a patient's therapy, detecting an emerging myelodysplasia and providing insights into the therapeutic response.
Patients undergoing stereotactic radiosurgery for brain metastases may show unexpected effects in the lesions after treatment with antibodies to PD-1. Assessments of clinical and radiologic changes need accurate interpretation in this growing patient population.
Housing mice in enriched environments with multiple stimuli modulated T-cell immunity and inhibited cancer progression. Enhanced immunity was mediated by hypothalamic BDNF, supporting the concept that manipulating a single gene in the brain can improve cancer immunotherapy.
Bispecific chimeric antigen receptors (CARs) have been systematically optimized to simultaneously target two clinically relevant antigens, CD19 and CD20, presenting a clinically applicable solution to antigen escape and facilitating the rational design of receptors with higher-level complexities.
Most patients with B-cell lymphoma are treated with mAbs to CD20, which might interfere with subsequent chimeric antigen receptor (CAR) T cells against CD20. However, function was preserved in vivo in the presence of clinically relevant rituximab concentrations and only modestly impaired in vitro.
Autophagy inhibition has been proposed for treatment of KRAS-driven cancer, but this strategy resulted in a protumorigenic feedback loop that activated TBK1 and induced PD-L1 expression. Therapeutic approaches that counteract this feedback may be necessary to limit pancreatic dysplasia.
Blocking phosphatidylserine (PS) with antibodies reprograms the tumor microenvironment from immunosuppressive to immunosupportive and reactivates innate and adaptive antitumor immunity. Combining PS targeting with immune checkpoint blockade improved the therapeutic efficacy of both approaches in two preclinical tumor models.
Insertion of the small transgene RIAD augmented the efficacy of CAR T cells in solid tumors by blocking the inhibitory activity of PKA. This reduced immunosuppression by adenosine and PGE2, while enhancing CAR T cells trafficking into tumors.
Epithelial tumors are thought to recapitulate an epithelial–mesenchymal transition during the transformation process. By assessing ESRP1 transcripts in melanomas, associations were found between more mesenchymal states, immune cytolytic activity, and checkpoint expression that may have implications for immunotherapy.