Matches in SemOpenAlex for { <https://semopenalex.org/work/W2742188140> ?p ?o ?g. }
- W2742188140 endingPage "1676" @default.
- W2742188140 startingPage "1666" @default.
- W2742188140 abstract "Understanding the mechanisms of acquired resistance to anti-PD-1 will allow development of better treatment strategies for cancer patients. This study evaluated potential mechanisms of acquired resistance to anti-PD-1 in longitudinally collected metastatic melanoma patient biopsies. Thirty-four metastatic melanoma biopsies were collected from 16 patients who had initially responded to either anti-PD-1 (n=13) alone or combination of anti-PD-1 and ipilimumab (n=3) and then progressed. Biopsies were taken prior to treatment (PRE, n=12) and following progression of disease (PROG, n=22). Immunohistochemistry was performed on all biopsies to detect CD8, FOXP3, PD-1 and VISTA expression on T-cells and PTEN, β-catenin, PD-L1, HLA-A, and HLA-DPB1 expression in the tumor. The majority of patients showed significantly increased density of VISTA+ lymphocytes from PRE to PROG (12/18) (P=0.009) and increased expression of tumor PD-L1 from PRE to PROG (11/18). Intratumoral expression of FOXP3+ lymphocytes significantly increased (P=0.018) from PRE to PROG (10/18). Loss of tumor PTEN and downregulation of tumor HLA-A from PRE to PROG were each identified in 5/18 and 4/18 PROG biopsies, respectively. Downregulation of HLA-DPB1 from PRE to PROG was present in 3/18 PROG biopsies, whereas nuclear β-catenin activation was only identified in 2/18 PROG biopsies. Negative immune checkpoint regulation by VISTA represents an important potential mechanism of acquired resistance in melanoma patients treated with anti-PD-1. Downregulation of HLA-associated antigen presentation also occurs with acquired resistance. Augmentation of the VISTA immune checkpoint pathway may hold promise as a therapeutic strategy in metastatic melanoma patients, particularly those failing anti-PD-1 therapy, and warrants assessment in clinical trials." @default.
- W2742188140 created "2017-08-17" @default.
- W2742188140 creator A5001606920 @default.
- W2742188140 creator A5022520811 @default.
- W2742188140 creator A5030883672 @default.
- W2742188140 creator A5035263718 @default.
- W2742188140 creator A5045360865 @default.
- W2742188140 creator A5071577704 @default.
- W2742188140 creator A5077475580 @default.
- W2742188140 creator A5081462567 @default.
- W2742188140 creator A5083061830 @default.
- W2742188140 creator A5083653505 @default.
- W2742188140 date "2017-12-01" @default.
- W2742188140 modified "2023-10-11" @default.
- W2742188140 title "Negative immune checkpoint regulation by VISTA: a mechanism of acquired resistance to anti-PD-1 therapy in metastatic melanoma patients" @default.
- W2742188140 cites W1498931318 @default.
- W2742188140 cites W1538902372 @default.
- W2742188140 cites W1572739876 @default.
- W2742188140 cites W1856892620 @default.
- W2742188140 cites W1901759988 @default.
- W2742188140 cites W2018167187 @default.
- W2742188140 cites W2023082289 @default.
- W2742188140 cites W2039123767 @default.
- W2742188140 cites W2046739604 @default.
- W2742188140 cites W2050574097 @default.
- W2742188140 cites W2084281756 @default.
- W2742188140 cites W2097288420 @default.
- W2742188140 cites W2103675014 @default.
- W2742188140 cites W2112601576 @default.
- W2742188140 cites W2113716683 @default.
- W2742188140 cites W2136498843 @default.
- W2742188140 cites W2161693332 @default.
- W2742188140 cites W2166932124 @default.
- W2742188140 cites W2171709048 @default.
- W2742188140 cites W2201379305 @default.
- W2742188140 cites W2254024193 @default.
- W2742188140 cites W2295795165 @default.
- W2742188140 cites W2301707196 @default.
- W2742188140 cites W2343253911 @default.
- W2742188140 cites W2465860350 @default.
- W2742188140 cites W2490333234 @default.
- W2742188140 cites W2513583837 @default.
- W2742188140 cites W2526607882 @default.
- W2742188140 cites W2748949248 @default.
- W2742188140 doi "https://doi.org/10.1038/modpathol.2017.89" @default.
- W2742188140 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28776578" @default.
- W2742188140 hasPublicationYear "2017" @default.
- W2742188140 type Work @default.
- W2742188140 sameAs 2742188140 @default.
- W2742188140 citedByCount "141" @default.
- W2742188140 countsByYear W27421881402017 @default.
- W2742188140 countsByYear W27421881402018 @default.
- W2742188140 countsByYear W27421881402019 @default.
- W2742188140 countsByYear W27421881402020 @default.
- W2742188140 countsByYear W27421881402021 @default.
- W2742188140 countsByYear W27421881402022 @default.
- W2742188140 countsByYear W27421881402023 @default.
- W2742188140 crossrefType "journal-article" @default.
- W2742188140 hasAuthorship W2742188140A5001606920 @default.
- W2742188140 hasAuthorship W2742188140A5022520811 @default.
- W2742188140 hasAuthorship W2742188140A5030883672 @default.
- W2742188140 hasAuthorship W2742188140A5035263718 @default.
- W2742188140 hasAuthorship W2742188140A5045360865 @default.
- W2742188140 hasAuthorship W2742188140A5071577704 @default.
- W2742188140 hasAuthorship W2742188140A5077475580 @default.
- W2742188140 hasAuthorship W2742188140A5081462567 @default.
- W2742188140 hasAuthorship W2742188140A5083061830 @default.
- W2742188140 hasAuthorship W2742188140A5083653505 @default.
- W2742188140 hasBestOaLocation W27421881401 @default.
- W2742188140 hasConcept C104317684 @default.
- W2742188140 hasConcept C121608353 @default.
- W2742188140 hasConcept C126322002 @default.
- W2742188140 hasConcept C127561419 @default.
- W2742188140 hasConcept C142724271 @default.
- W2742188140 hasConcept C143998085 @default.
- W2742188140 hasConcept C167672396 @default.
- W2742188140 hasConcept C190283241 @default.
- W2742188140 hasConcept C203014093 @default.
- W2742188140 hasConcept C204232928 @default.
- W2742188140 hasConcept C2777609662 @default.
- W2742188140 hasConcept C2777658100 @default.
- W2742188140 hasConcept C2777701055 @default.
- W2742188140 hasConcept C2778326572 @default.
- W2742188140 hasConcept C2779727006 @default.
- W2742188140 hasConcept C2780851360 @default.
- W2742188140 hasConcept C502942594 @default.
- W2742188140 hasConcept C55493867 @default.
- W2742188140 hasConcept C71924100 @default.
- W2742188140 hasConcept C86554907 @default.
- W2742188140 hasConcept C86803240 @default.
- W2742188140 hasConcept C8891405 @default.
- W2742188140 hasConceptScore W2742188140C104317684 @default.
- W2742188140 hasConceptScore W2742188140C121608353 @default.
- W2742188140 hasConceptScore W2742188140C126322002 @default.
- W2742188140 hasConceptScore W2742188140C127561419 @default.
- W2742188140 hasConceptScore W2742188140C142724271 @default.
- W2742188140 hasConceptScore W2742188140C143998085 @default.
- W2742188140 hasConceptScore W2742188140C167672396 @default.