PMID- 35162988
OWN - NLM
STAT- MEDLINE
DCOM- 20220408
LR  - 20220408
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 3
DP  - 2022 Jan 19
TI  - GILT Expression in Human Melanoma Cells Enhances Generation of Antigenic Peptides 
      for HLA Class II-Mediated Immune Recognition.
LID - 10.3390/ijms23031066 [doi]
LID - 1066
AB  - Melanoma is an aggressive skin cancer that has become increasingly prevalent in 
      western populations. Current treatments such as surgery, chemotherapy, and 
      high-dose radiation have had limited success, often failing to treat late stage, 
      metastatic melanoma. Alternative strategies such as immunotherapies have been 
      successful in treating a small percentage of patients with metastatic disease, 
      although these treatments to date have not been proven to enhance overall 
      survival. Several melanoma antigens (Ags) proposed as targets for 
      immunotherapeutics include tyrosinase, NY-ESO-1, gp-100, and Mart-1, all of which 
      contain both human leukocyte antigen (HLA) class I and class II-restricted 
      epitopes necessary for immune recognition. We have previously shown that an 
      enzyme, gamma-IFN-inducible lysosomal thiol-reductase (GILT), is abundantly 
      expressed in professional Ag presenting cells (APCs), but absent or expressed at 
      greatly reduced levels in many human melanomas. In the current study, we report 
      that increased GILT expression generates a greater pool of antigenic peptides in 
      melanoma cells for enhanced CD4+ T cell recognition. Our results suggest that the 
      induction of GILT in human melanoma cells could aid in the development of a novel 
      whole-cell vaccine for the enhancement of immune recognition of metastatic 
      melanoma.
FAU - Hathaway-Schrader, Jessica D
AU  - Hathaway-Schrader JD
AD  - Department of Microbiology and Immunology, Hollings Cancer Center, Children's 
      Research Institute, Medical University of South Carolina, 173 Ashley Avenue, 
      Charleston, SC 29425, USA.
FAU - Norton, Duncan
AU  - Norton D
AD  - Department of Microbiology and Immunology, Hollings Cancer Center, Children's 
      Research Institute, Medical University of South Carolina, 173 Ashley Avenue, 
      Charleston, SC 29425, USA.
FAU - Hastings, Katherine
AU  - Hastings K
AD  - Department of Microbiology and Immunology, Hollings Cancer Center, Children's 
      Research Institute, Medical University of South Carolina, 173 Ashley Avenue, 
      Charleston, SC 29425, USA.
FAU - Doonan, Bently P
AU  - Doonan BP
AD  - Department of Microbiology and Immunology, Hollings Cancer Center, Children's 
      Research Institute, Medical University of South Carolina, 173 Ashley Avenue, 
      Charleston, SC 29425, USA.
AD  - UF Brain Tumor Immunotherapy Program, Department of Oncology, University of 
      Florida, Gainesville, FL 3260, USA.
FAU - Fritz, Shaun Tompkins
AU  - Fritz ST
AD  - Department of Microbiology and Immunology, Hollings Cancer Center, Children's 
      Research Institute, Medical University of South Carolina, 173 Ashley Avenue, 
      Charleston, SC 29425, USA.
FAU - Bethard, Jennifer R
AU  - Bethard JR
AD  - Department of Cell and Molecular Pharmacology and Experimental Therapeutics, 
      Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, 
      USA.
FAU - Blum, Janice S
AU  - Blum JS
AD  - Department of Microbiology and Immunology, School of Medicine, Indiana 
      University, Indianapolis, IN 46202, USA.
FAU - Haque, Azizul
AU  - Haque A
AUID- ORCID: 0000-0002-6386-9390
AD  - Department of Microbiology and Immunology, Hollings Cancer Center, Children's 
      Research Institute, Medical University of South Carolina, 173 Ashley Avenue, 
      Charleston, SC 29425, USA.
LA  - eng
GR  - R01 CA129560 and R01 CA129560-S1 to A. Haque/NH/NIH HHS/United States
PT  - Journal Article
DEP - 20220119
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (HLA Antigens)
RN  - 0 (Peptides)
RN  - 0 (Sulfhydryl Compounds)
RN  - EC 1.8.- (Oxidoreductases Acting on Sulfur Group Donors)
SB  - IM
MH  - Antigen Presentation
MH  - Antigens, Neoplasm
MH  - HLA Antigens
MH  - Humans
MH  - Lysosomes/metabolism
MH  - *Melanoma
MH  - Oxidoreductases Acting on Sulfur Group Donors/metabolism
MH  - Peptides
MH  - *Sulfhydryl Compounds
PMC - PMC8835040
OTO - NOTNLM
OT  - Ag presenting cells (APCs)
OT  - CD4+ T cells
OT  - cathepsins
OT  - gamma-IFN-inducible lysosomal thiol-reductase (GILT)
OT  - human leukocyte antigen (HLA) class II
OT  - melanoma
COIS- The authors have no financial conflict of interest.
EDAT- 2022/02/16 06:00
MHDA- 2022/04/09 06:00
PMCR- 2022/01/19
CRDT- 2022/02/15 01:16
PHST- 2021/12/31 00:00 [received]
PHST- 2022/01/11 00:00 [accepted]
PHST- 2022/02/15 01:16 [entrez]
PHST- 2022/02/16 06:00 [pubmed]
PHST- 2022/04/09 06:00 [medline]
PHST- 2022/01/19 00:00 [pmc-release]
AID - ijms23031066 [pii]
AID - ijms-23-01066 [pii]
AID - 10.3390/ijms23031066 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Jan 19;23(3):1066. doi: 10.3390/ijms23031066.