2015
DOI: 10.1074/jbc.m115.676130
|View full text |Cite
|
Sign up to set email alerts
|

Multiple Structural and Epigenetic Defects in the Human Leukocyte Antigen Class I Antigen Presentation Pathway in a Recurrent Metastatic Melanoma Following Immunotherapy

Abstract: Background: Understanding the mechanism of tumor immune resistance can help design effective cancer immunotherapy. Results: A novel tapasin mutation, haplotype loss, and HLA epigenetic repression were identified and characterized in a single tumor population. Conclusion:The first evidence for combined HLA genetic and epigenetic defects in malignant cells was presented. Significance: Combinatorial immunotherapy harnessing T cell responses and DNA demethylation may counteract tumor immune resistance.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
3
1
1

Citation Types

1
46
0

Year Published

2016
2016
2023
2023

Publication Types

Select...
9
1

Relationship

1
9

Authors

Journals

citations
Cited by 60 publications
(48 citation statements)
references
References 54 publications
1
46
0
Order By: Relevance
“…33 In addition, a recent report has shown a novel germline frameshift mutation in a single population of human melanomas, resulting in loss of tapasin, and expression could not be restored by IFNg treatment. 34 Our results raised another intriguing question concerning HLA types and tapasin dependency. It is known that loss of tapasin generally leads to a decrease in HLA surface expression, but the dependency on tapasin differs across HLA-class I allotypes.…”
Section: Discussionmentioning
confidence: 79%
“…33 In addition, a recent report has shown a novel germline frameshift mutation in a single population of human melanomas, resulting in loss of tapasin, and expression could not be restored by IFNg treatment. 34 Our results raised another intriguing question concerning HLA types and tapasin dependency. It is known that loss of tapasin generally leads to a decrease in HLA surface expression, but the dependency on tapasin differs across HLA-class I allotypes.…”
Section: Discussionmentioning
confidence: 79%
“…Opposite to their debated role in the course of PD-1 therapy, more univocal evidence seems to be available concerning the functional relevance of HLA class I molecules in the course of CTLA-4 blockade therapy. Indeed, multiple molecular mechanisms, which can be also independent from B2M gene alterations, have been reported to drive loss or downregulation of HLA class I molecules expression on melanoma cells (40), generating a reduced effectiveness of therapy with ipilimumab (40,41). In this scenario, the upregulation of HLA class I molecules expression on melanoma cells induced by treatment in our NIBIT-M4 study seems to suggest that combined treatment with guadecitabine and ipilimumab may contribute to improve the clinical efficacy of CTLA-4 blockade.…”
Section: Discussionmentioning
confidence: 99%
“…In Europe and America, TNBC constitutes 10 -17 % of breast cancer [9]. The disease generally occurs in premenopausal young women, and the prognosis is closely related to disease stage, tumor grade, socio-economic status of the patient, and ethnic nationality [10].…”
Section: Discussionmentioning
confidence: 99%