Neoantigen landscape dynamics during human melanoma–T-cell interactions
Tumors and their infiltrating T-cell populations reciprocally pressure each other—tumors to avoid recognition, and T cells to spot neoantigens. Longitudinal examination allowed tracking of the dynamic emergence–response relationship between neoepitope expression and T-cell reactivity.
Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy
Image source: https://en.wikipedia.org/wiki/PTK2
For the immune system to successfully eradicate tumors, T cells must first penetrate them. Jiang and colleagues found that FAK induces fibrosis. Inhibiting FAK allowed immune cells to infiltrate, greatly increasing the effectiveness of various immuno- and chemotherapies.
Jiang H, Hegde S, Knolhoff BL, Zhu Y, Herndon JM, Meyer MA, et al. Nat Med 2016;22:851–60.
Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy
Multiple approaches to tumor vaccines are in clinical trials. Kranz and colleagues devised an RNA nanoparticle that, regardless of the antigen, is taken up by DCs. The ensuing innate and adaptive immune responses successfully rejected tumors in an IFNα-dependent process.
Kranz LM, Diken M, Haas H, Kreiter S, Loquai C, Reuter KC, et al. Nature 2016;16;534:396–401.
Identification of shared TCR sequences from T cells in human breast cancer using emulsion RT-PCR
Image source: Munson et al., PNAS
Knowledge of the T-cell receptors used in antitumor responses could enhance immunotherapy. Munson and colleagues developed an enhanced single-cell emulsion RT-PCR assay that identifies TCR pairs, giving insight into antitumor TCR repertoires and potentially identifying tumor antigens.
Mutations associated with acquired resistance to PD-1 blockade in melanoma
Immune-based cancer therapies are promising, but not always permanent, with potential outgrowth of tumor cells insensitive to the treatment. Genetic analysis of resistance to a checkpoint blockade revealed mutations that led to loss of IFNγ expression or HLA surface expression.
Inhibition of T cell receptor signaling by cholesterol sulfate, a naturally occurring derivative of membrane cholesterol
Successful cancer immunotherapies require a firm understanding of the environmental signals affecting T-cell activation and regulation. Wang and colleagues found a ubiquitous cholesterol derivative that physiologically functions to inhibit TCR activation by disrupting the TCR-CD3 nanoclusters necessary for T-cell activation.
Wang F, Beck-García K, Zorzin C, Schamel WW, Davis MM. Nat Immunol 2016;17:844–50.
- ©2016 American Association for Cancer Research.
Volume 4, Issue 9
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- Neoantigen landscape dynamics during human melanoma–T-cell interactions
- Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy
- Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy
- Identification of shared TCR sequences from T cells in human breast cancer using emulsion RT-PCR
- Mutations associated with acquired resistance to PD-1 blockade in melanoma
- Inhibition of T cell receptor signaling by cholesterol sulfate, a naturally occurring derivative of membrane cholesterol
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