What We're Reading
Cancer Immunol Res June 1 2018 6 (6) 629-629;
Development of sarcoid-like granulomatosis of the lung after immune-checkpoint inhibition was observed in four patients with different tumor types. This manifestation had distinct clinical, imaging, and histological features, which characterized it as an immune-related adverse event.
An improved peptide prediction tool for murine MHC class I presentation, NetH2pan, was created and cross-validated on MMTV-PyMT tumors. Its predictive powers were more accurate than other tools, enabling epitope discovery in the FVB and other mouse strains.
The pro-inflammatory cytokine IL17A has antitumor effects in certain subtypes of non–small cell lung cancer. Mice whose tumors were infiltrated with IL17A-expressing T cells were associated with increased lung cancer latency and had fewer metastasis.
Type I interferon (IFN-I) inhibits tumor growth and activates antitumor responses. HER2-driven tumors in mice lacking IFN-I receptor were more aggressive, more vascularized, and were enriched in stem cells, suggesting that IFN-I exerts key control over tumor progression.
Expression of tissue factor (TF) on the cancer cells and tumor neovasculature of triple-negative breast cancer provides a target for immunotherapy. An improved TF-targeting second-generation immunoconjugate (called L-ICON1) was tested for immunotherapy of this malignancy in preclinical mouse models.
Combination rIL21 and anti–PD-1/anti–Tim-3 additively enhanced NK cell responses in mice bearing MHCclass I–deficient tumors. This combination facilitated NK effector functions in cancer patients, highlighting its therapeutic potential for patients with MHC class I–deficient tumors.
In a mouse model of chronic lymphocytic leukemia, production of secretory IgM led to more MDSCs, fewer T cells, and shorter survival times for the mice. Thus, secretory IgM may aggravate the progression of this cancer.
Pazopanib, a kinase inhibitor that targets angiogenesis, primed dendritic cells from patients with metastatic renal cell carcinoma and healthy donors. The resultant immune response indicates that this could be exploited to improve outcomes for patients undergoing combination immunotherapy.
PPARγ deficiency in myeloid cells reduced the efficacy of GVAX cancer vaccines, altered DC gene expression and function, and decreased the ratio of vaccine-induced CD8+ T cells to Tregs. Correspondingly, PPARγ agonists improved the efficacy of cancer immunotherapy.
It may be safer to improve adoptive T-cell therapy through increased signaling rather than increased antigen affinity of the TCRs. Modifying intracellular signaling enhanced the proliferation and persistence of CTLs while improving antitumor efficacy.
In CML patients treated with tyrosine kinase inhibitors, KIR alleles were associated with patient outcome. The combination of alleles at KIR3DL1 and HLA-B loci were found to predict the therapeutic effects of tyrosine kinase inhibitor therapy.