scholarly journals Mismatch Repair Protein Deficiency Is a Risk Factor for Aberrant Expression of HLA Class I Molecules: A Putative "Adaptive Immune Escape" Phenomenon

2017 ◽  
Vol 37 (3) ◽  
pp. 1289-1296 ◽  
2012 ◽  
Vol 131 (8) ◽  
pp. 1828-1836 ◽  
Author(s):  
Renske A. de Jong ◽  
Annemarie Boerma ◽  
H. Marike Boezen ◽  
Marian J.E. Mourits ◽  
Harry Hollema ◽  
...  

2020 ◽  
Vol 8 (1) ◽  
pp. e000410
Author(s):  
Jonathan S Cebon ◽  
Martin Gore ◽  
John F Thompson ◽  
Ian D Davis ◽  
Grant A McArthur ◽  
...  

BackgroundTo compare the clinical efficacy of New York Esophageal squamous cell carcinoma-1 (NY-ESO-1) vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in a randomized, double-blind phase II study in participants with fully resected melanoma at high risk of recurrence.MethodsParticipants with resected stage IIc, IIIb, IIIc and IV melanoma expressing NY-ESO-1 were randomized to treatment with three doses of NY-ESO-1/ISCOMATRIX or ISCOMATRIX adjuvant administered intramuscularly at 4-week intervals, followed by a further dose at 6 months. Primary endpoint was the proportion free of relapse at 18 months in the intention-to-treat (ITT) population and two per-protocol populations. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), safety and NY-ESO-1 immunity.ResultsThe ITT population comprised 110 participants, with 56 randomized to NY-ESO-1/ISCOMATRIX and 54 to ISCOMATRIX alone. No significant toxicities were observed. There were no differences between the study arms in relapses at 18 months or for median time to relapse; 139 vs 176 days (p=0.296), or relapse rate, 27 (48.2%) vs 26 (48.1%) (HR 0.913; 95% CI 0.402 to 2.231), respectively. RFS and OS were similar between the study arms. Vaccine recipients developed strong positive antibody responses to NY-ESO-1 (p≤0.0001) and NY-ESO-1-specific CD4+and CD8+responses. Biopsies following relapse did not demonstrate differences in NY-ESO-1 expression between the study populations although an exploratory study demonstrated reduced (NY-ESO-1)+/Human Leukocyte Antigen (HLA) class I+double-positive cells in biopsies from vaccine recipients performed on relapse in 19 participants.ConclusionsThe vaccine was well tolerated, however, despite inducing antigen-specific immunity, it did not affect survival endpoints. Immune escape through the downregulation of NY-ESO-1 and/or HLA class I molecules on tumor may have contributed to relapse.


2014 ◽  
Vol 38 (3) ◽  
pp. 192-199
Author(s):  
R. Carretero ◽  
H. Gil-Julio ◽  
F. Vázquez-Alonso ◽  
F. Garrido ◽  
J. Castiñeiras ◽  
...  

Blood ◽  
2009 ◽  
Vol 113 (2) ◽  
pp. 347-357 ◽  
Author(s):  
Aurore Brémond ◽  
Ophélie Meynet ◽  
Karim Mahiddine ◽  
Sylvie Coito ◽  
Mélanie Tichet ◽  
...  

Abstract By presenting antigenic peptides on the cell surface, human leukocyte antigen (HLA) class I molecules are critical for immune defense. Their surface density determines, to a large extent, the level of CD8+ T cell–dependent immune reactions; their loss is a major mechanism of immune escape. Therefore, powerful processes should regulate their surface expression. Here we document the mechanisms used by CD99 to mediate HLA class I modulation. Up-regulation of HLA class I by IFN-γ requires CD99. In the trans Golgi network (TGN), and up to the cell surface, CD99 and HLA class I are physically associated via their transmembrane domain. CD99 also binds p230/golgin-245, a coiled-coil protein that recycles between the cytosol and buds/vesicles of the TGN and which plays a fundamental role in trafficking transport vesicles. p230/golgin-245 is anchored within TGN membranes via its Golgin-97, RanBP1, IMh1p, P230 (GRIP) domain and the overexpression of which leads to surface and intracellular down-modulation of HLA class I molecules.


Sign in / Sign up

Export Citation Format

Share Document