Spatially resolved gene expression patterns are emerging as a key component of medical studies,including companion diagnostics,but technologies for quantification and multiplexing are limited.We present a method to pe...Spatially resolved gene expression patterns are emerging as a key component of medical studies,including companion diagnostics,but technologies for quantification and multiplexing are limited.We present a method to perform spatially resolved and multiplexed microRNA(miRNA)measurements from formalin-fixed,paraffin-embedded(FFPE)tissue.Using nanoliter well arrays to pixelate the tissue section and photopatterned hydrogels to quantify miRNA,we identified differentially expressed miRNAs in tumors from a genetically engineered mouse model for non-small cell lung cancer(K-ras&(LSL-G12D/+);p53^(fl/fl)).This technology could be used to quantify heterogeneities in tissue samples and lead to informed,biomarker-based diagnostics.展开更多
Gastric cancer(GC)is the fifth most common cancer worldwide.In approximately 10%of GC cases,cancer cells show ubiquitous and monoclonal Epstein-Barr virus(EBV)infection.A significant feature of EBV-associated GC(EBVaG...Gastric cancer(GC)is the fifth most common cancer worldwide.In approximately 10%of GC cases,cancer cells show ubiquitous and monoclonal Epstein-Barr virus(EBV)infection.A significant feature of EBV-associated GC(EBVaGC)is high lymphocytic infiltration and high expression of immune checkpoint proteins,including programmed death-ligand 1(PD-L1).This highlights EBVaGC as a strong candidate for immune checkpoint blockade therapy.Indeed,several recent studies have shown that EBV positivity in GC correlates with positive response to programmed cell death protein 1(PD-1)/PD-L1 blockade therapy.Understanding the mechanisms that control PD-L1 expression in EBVaGC can indicate new predictive biomarkers for immunotherapy,as well as therapeutic targets for combination therapy.Various mechanisms have been implicated in PD-L1 expression regulation,including structural variations,post-transcriptional control,oncogenic activation of intrinsic signaling pathways,and increased sensitivity to extrinsic signals.This review provides the most recent updates on the multilayered control of PD-L1 expression in EBVaGC.展开更多
基金This work was supported by NIH Grant 1R01CA235740-01A1(P.S.D.,F.J.S.)partially by the Cancer Center Support(core)Grant P30-CA14051 from the National Cancer Institute(P.S.D.,F.J.S.)+4 种基金a Ford Foundation Postdoctoral Fellowship(A.M.T.)a Ludwig Center Fund Postdoctoral Fellowship(A.M.T.)NIHNRSA 5T32HL007893-20(W.C.Z.)the NIH-YALE SPORE in Lung Cancer P50CA196530-03S1(F.J.S.)NIH-NIBIB Grant 5R21EB024101-02(P.S.D.).
文摘Spatially resolved gene expression patterns are emerging as a key component of medical studies,including companion diagnostics,but technologies for quantification and multiplexing are limited.We present a method to perform spatially resolved and multiplexed microRNA(miRNA)measurements from formalin-fixed,paraffin-embedded(FFPE)tissue.Using nanoliter well arrays to pixelate the tissue section and photopatterned hydrogels to quantify miRNA,we identified differentially expressed miRNAs in tumors from a genetically engineered mouse model for non-small cell lung cancer(K-ras&(LSL-G12D/+);p53^(fl/fl)).This technology could be used to quantify heterogeneities in tissue samples and lead to informed,biomarker-based diagnostics.
基金Slack FJ acknowledges the NCI Outstanding Investigator Award(R35CA232105)the support of the Ludwig Institute at Harvard and the V Foundation.
文摘Gastric cancer(GC)is the fifth most common cancer worldwide.In approximately 10%of GC cases,cancer cells show ubiquitous and monoclonal Epstein-Barr virus(EBV)infection.A significant feature of EBV-associated GC(EBVaGC)is high lymphocytic infiltration and high expression of immune checkpoint proteins,including programmed death-ligand 1(PD-L1).This highlights EBVaGC as a strong candidate for immune checkpoint blockade therapy.Indeed,several recent studies have shown that EBV positivity in GC correlates with positive response to programmed cell death protein 1(PD-1)/PD-L1 blockade therapy.Understanding the mechanisms that control PD-L1 expression in EBVaGC can indicate new predictive biomarkers for immunotherapy,as well as therapeutic targets for combination therapy.Various mechanisms have been implicated in PD-L1 expression regulation,including structural variations,post-transcriptional control,oncogenic activation of intrinsic signaling pathways,and increased sensitivity to extrinsic signals.This review provides the most recent updates on the multilayered control of PD-L1 expression in EBVaGC.