What We're Reading
Cancer Immunol Res November 1 2016 4 (11) 893-893;
A patient with testicular germ cell tumor (TGCT) responded to PD-1 blockade. A T-cell signature in the TGCT cohort of The Cancer Genome Atlas predicted benefit from immunotherapy and suggested an immunoinhibitory role for α-fetoprotein.
Analysis of Hodgkin lymphomas revealed frequent reduction/loss of antigen-presentation proteins and 9p24.1/PD-L1/PD-L2 alterations. These immune evasion mechanisms had independent prognostic value after frontline therapy and prompt speculation regarding alternative mechanisms of action of PD-1 blockade.
Intestinal adenomas are driven by inflammation in familial adenomatous polyposis (FAP) and its APCMin/+ mouse model. FAP patients have reduced intestinal retinoic acid; restoring it in mice ameliorated inflammation and reduced tumor burden, suggesting therapeutic approaches for FAP.
The population-based data presented in this study support a possible role for microRNA let-7a in the suppression of antitumor immunity in colorectal cancer patients. This may have implications for expanding the benefit of immunotherapy through targeting microRNAs.
Kinome screens revealed EGFR and MEK as key to reduced MHCI expression on many tumors. FDA-approved inhibitors of these kinases increased surface MHC-I, providing a rationale for clinically testing similar kinase inhibitors with immunotherapies dependent on MHC-I.
GM-CSF is a component of many combination immunotherapeutic strategies. This phase I clinical study investigated GM-CSF effects on circulating and intratumoral immune cells, and found that infiltration of antigen-presenting cells was unaffected, but intratumoral CD8+ T cells increased.
Mutational load, by whole exome sequencing, can correlate with immunotherapy responses. Assessing melanoma mutational load of a fraction of the genome, by hybrid capture-based NGS, provided an accurate surrogate for WES determinations, and predicted response to anti-PD-1.
Tumor-associated neutrophils found in pancreatic tumors were dependent on CXCR2 ligands. The signaling pathways that induce CXCR2 ligand expression were identified, and preventing neutrophil accumulation allowed activated T cells access to the tumor, making CXCR2 a potential therapeutic target.
IL2 is not commonly used as immunotherapy due to its induction of regulatory T cells and dangerous cytokine storms. The IL2 variant, F42K, promoted the expansion and activation of antitumor NK cells without inducing highly suppressive Tregs.