Editorial
Glenn Dranoff
Cancer Immunol Res April 1 2014 2 (4) 287-287; DOI:10.1158/2326-6066.CIR-14-0043
Miller and colleagues analyzed archived annotated breast tumors and evaluated patient data in three public cohorts; they found an inverse association between JAK2 mRNA and risk of recurrence and a correlation between JAK2 expression, improved outcomes, and infiltrating T cells.
Black and colleagues identify, for the first time, that low-avidity antitumor T cells are ineffective due to increased expression of proapoptotic proteins promoting activation-induced T-cell death, which can be overcome by TNFR agonists, implicating their use in cancer immunotherapy.
MacFarlane and colleagues show that tumor resection reverses PD-1 expression on peripheral blood (PB) immune cells and suggest that PD-1 blockade for renal cell carcinoma patients with PD-1 expression on PB cells would be most effective prior to surgery, especially in early-stage cancer.
Charbonneau and colleagues analyzed the genotypes and outcomes of 10,084 women from Ovarian Cancer Association Consortium studies and identified polymorphisms in regulatory T-cell genes associated with the survival of patients with endometrioid (IL2RA) and clear cell (CTLA4) invasive epithelial ovarian cancer.
Matsuzaki, Tsuji, and colleagues show that a unique subset of NY-ESO-1–specific CD4+ T cells directly recognize cancer cells and short 8-9-mer peptides via nonclassical pathways involving proteasomal degradation, transporter-associated antigen processing (TAP)–mediated peptide transport, and endosomal recycling.
Vella and colleagues show that inhibition of BRAF (dabrafenib) had no effect on healthy donor T cells and monocyte-derived dendritic cells (MoDC), but that MEK inhibition (trametinib) suppressed T-cell proliferation, cytokine production, antigen-specific expansion, and MoDC cross-presentation.
Using tissue microarrays containing 105 triple-negative breast cancer (TNBC) specimens, Mittendorf and colleagues show that 20% of the TNBC specimens express PD-L1, half have lost PTEN, and inhibitors of PI3K pathway decrease PD-L1 expression, providing a rationale for therapeutic targeting of PD-L1 for TNBC.
Yao and colleagues surveyed the expression and methylation of CT antigens and clinicopathologic features of ten cancers in The Cancer Genome Atlas RNAseq datasets, identifying multiple tumor subtype-specific CT antigens to be studied as potential biomarkers and targets for immunotherapy.