Distinct Molecular Mechanisms of Altered HLA Class II Expression in Malignant Melanoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Melanoma Cell Lines, Cell Culture and Treatment
2.2. qPCR Analysis
2.3. Monoclonal Antibodies
2.4. Flow Cytometry
2.5. Analysis of CIITA Methylation Pattern
2.6. Immunohistochemistry of Tissue Microarrays (TMAs)
2.7. Statistical Analysis
2.8. Bioinformatics Evaluation of Clinical Relevance
3. Results
3.1. HLA Class II Expression in Melanoma Cells
3.2. Correlation of Heterogeneous HLA Class II Surface Antigen Expression with Altered APM Component Expression
3.3. Distinct Responsiveness of Melanoma Cells to IFN-γ
3.4. Upregulation of HLA Class II Surface Expression upon Treatment of Melanoma Cells with Epigenetic Drugs
3.5. CIITA Expression as a Major Regulator of the HLA Class II Surface Expression
3.6. Correlation of HLA Class II APM Components and Immune Cell Infiltration with Clinical Relevance
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Samples | HLA-II APM | n 1 | High | Medium | Low | Negative |
---|---|---|---|---|---|---|
Melanoma lesions | HLA class II | 326 | 37 (11.33%) | 68 (20.86%) | 95 (29.14%) | 126 (38.65%) |
HLA-DO | 294 | 0 | 13 (4.42%) | 26 (8.84%) | 255 (86.73%) | |
CIITA tumor | 314 | 0 | 1 (0.32%) | 23 (7.32%) | 284 (90.45%) | |
CIITA lymph. | 314 | 12 (3.82%) | 55 (17.52%) | 139 (44.27%) | 108 (34.39%) | |
Melanoma cell lines | HLA class II | 47 | 4 (8.51%) | 13 (27.66%) | 5 (10.64%) | 25 (53.19%) |
Cell Line | qPCR 1 | Flow Cytometry 2 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
CIITA | HLA-DRa | HLA pan li | Cathepsin | HLA-DMa | HLA-DMb | HLA-DOA | HLA-DOB | CLIP | Classification | % Positive | |
melanocytes | 2 | 2 | 3 | 3 | 3 | 2 | 1 | 1 | 2 | neg. | |
HaCAT | 2 | 2 | 3 | 4 | 3 | 2 | 1 | 2 | 2 | neg. | |
BUF836 | 1 | 2 | 3 | 3 | 2 | 2 | 1 | 1 | 3 | neg. | |
Mel 624 | 1 | 1 | 1 | 2 | 3 | 2 | 1 | 1 | 1 | neg. | |
BUF1495 | 1 | 1 | 2 | 3 | 3 | 3 | 1 | 1 | 1 | neg. | |
BUF1286 | 1 | 1 | 2 | 3 | 3 | 3 | 2 | 1 | 1 | neg. | |
BUF1182 | 1 | 1 | 2 | 1 | 3 | 2 | 1 | 1 | 1 | neg. | |
BUF553b | 1 | 1 | 1 | 3 | 3 | 2 | 1 | 1 | 1 | neg. | |
FM6 | 2 | 1 | 3 | 3 | 3 | 2 | 1 | 2 | 3 | neg. | |
BUF1330 | 1 | 1 | 2 | 3 | 3 | 3 | 1 | 1 | 1 | neg. | |
BUF501 ATC | 1 | 1 | 2 | 3 | 3 | 2 | 1 | 1 | 1 | neg. | |
BUF1011 | 1 | 1 | 2 | 2 | 3 | 2 | 1 | 1 | 2 | neg. | |
BUF1195 | 1 | 1 | 1 | 1 | 2 | 1 | 1 | 1 | 1 | neg. | |
BUF1383 | 1 | 1 | 1 | 3 | 2 | 1 | 1 | 1 | 1 | neg. | |
FM81 | 1 | 1 | 1 | 3 | 3 | 3 | 2 | 2 | 1 | neg. | |
BUF1402 | 1 | 1 | 2 | 2 | 3 | 2 | 1 | 1 | 1 | neg. | |
BUF1287 | 2 | 3 | 5 | 3 | 3 | 2 | 2 | 1 | 3 | neg. | |
1727D | 2 | 3 | 3 | 3 | 3 | 3 | 1 | 1 | 2 | neg. | |
SK Mel29 1 | 2 | 2 | 2 | 2 | 3 | 2 | 1 | 2 | 1 | neg. | |
BUF1280 | 1 | 1 | 1 | 1 | 2 | 1 | 1 | 1 | 1 | neg. | |
Brooks 86 | 1 | 1 | 1 | 3 | 3 | 2 | 1 | 1 | 1 | neg. | |
UKRV Mel14a | 2 | 1 | 2 | 2 | 3 | 2 | 1 | 3 | 1 | neg. | |
BUF1379 | 1 | 1 | 2 | 2 | 3 | 2 | 1 | 1 | 1 | neg. | |
COLO 857 | 1 | 1 | 2 | 2 | 2 | 2 | 1 | 1 | 2 | neg. | |
NA-8 | 1 | 1 | 2 | 2 | 3 | 1 | 1 | 1 | 1 | neg. | |
BUF1520 | 1 | 1 | 3 | 2 | 2 | 2 | 1 | 1 | 3 | neg. | |
BUF624 | 1 | 2 | 2 | 3 | 3 | 2 | 1 | 1 | 2 | neg. | |
WM1862 | 1 | 2 | 3 | 3 | 3 | 2 | 1 | 2 | 2 | low | 11.9 |
MZ Mel3 | 2 | 4 | 3 | 2 | 3 | 3 | 1 | 1 | 3 | low | 13.3 |
M17 | 3 | 4 | 4 | 3 | 3 | 3 | 3 | 1 | 4 | low | 11.5 |
FM82 | 2 | 3 | 3 | 2 | 2 | 1 | 1 | 1 | 4 | low | 3.5 |
BUF1088 | 1 | 1 | 2 | 3 | 3 | 3 | 2 | 1 | 2 | low | 13.7 |
FM79 | 2 | 3 | 3 | 1 | 4 | 3 | 2 | 2 | 3 | med. | 23.3 |
BUF537 | 3 | 4 | 4 | 3 | 4 | 3 | 1 | 1 | 4 | med. | 27.4 |
FM28 | 3 | 4 | 4 | 3 | 4 | 3 | 2 | 2 | 3 | med. | 24.9 |
WM39 | 2 | 4 | 4 | 3 | 3 | 2 | 1 | 2 | 4 | med. | all |
FM3 | 4 | 5 | 5 | 2 | 4 | 4 | 4 | 3 | 5 | med. | 35.8 |
MKR | 3 | 4 | 4 | 2 | 4 | 2 | 2 | 1 | 4 | med. | 58.4 |
WM1552c | 1 | 2 | 1 | 3 | 3 | 3 | 2 | 2 | 1 | med. | all |
2058 Brooks | 2 | 4 | 4 | 4 | 3 | 2 | 2 | 1 | 4 | med. | all |
BUF526 | 2 | 3 | 4 | 2 | 3 | 2 | 1 | 2 | 5 | med. | all |
BUF1317 | 2 | 3 | 4 | 2 | 3 | 2 | 1 | 2 | 4 | med. | all |
GR-M | 3 | 4 | 4 | 3 | 3 | 2 | 1 | 2 | 4 | med. | all |
Mel1359 | 3 | 4 | 4 | 3 | 4 | 4 | 3 | 2 | 4 | med. | all |
Mel JUSO | 4 | 5 | 5 | 1 | 4 | 4 | 4 | 2 | 5 | med. | all |
COLO794 | 3 | 4 | 5 | 3 | 4 | 4 | 2 | 2 | 4 | high | all |
MZMel2 | 4 | 5 | 5 | 2 | 4 | 4 | 4 | 3 | 5 | high | all |
ZKR | 3 | 4 | 5 | 2 | 4 | 4 | 4 | 2 | 5 | high | all |
BUF1102 | 3 | 5 | 5 | 1 | 4 | 3 | 4 | 2 | 5 | high | all |
HLA Component | Melanoma Cells | ||
---|---|---|---|
High | Medium | Negative | |
CIITA | 3 | 21 | 23 |
CLIP | 16 | 13 | 18 |
pan-li | 16 | 23 | 8 |
HLA-DRa | 15 | 11 | 21 |
HLA-DOA | 5 | 12 | 30 |
HLA-DOB | 0 | 19 | 28 |
cathepsin S | 1 | 40 | 6 |
HLA-DMa | 11 | 36 | 0 |
HLA-DMb | 6 | 36 | 5 |
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Meyer, S.; Handke, D.; Mueller, A.; Biehl, K.; Kreuz, M.; Bukur, J.; Koehl, U.; Lazaridou, M.-F.; Berneburg, M.; Steven, A.; et al. Distinct Molecular Mechanisms of Altered HLA Class II Expression in Malignant Melanoma. Cancers 2021, 13, 3907. https://doi.org/10.3390/cancers13153907
Meyer S, Handke D, Mueller A, Biehl K, Kreuz M, Bukur J, Koehl U, Lazaridou M-F, Berneburg M, Steven A, et al. Distinct Molecular Mechanisms of Altered HLA Class II Expression in Malignant Melanoma. Cancers. 2021; 13(15):3907. https://doi.org/10.3390/cancers13153907
Chicago/Turabian StyleMeyer, Stefanie, Diana Handke, Anja Mueller, Katharina Biehl, Markus Kreuz, Jürgen Bukur, Ulrike Koehl, Maria-Filothei Lazaridou, Mark Berneburg, André Steven, and et al. 2021. "Distinct Molecular Mechanisms of Altered HLA Class II Expression in Malignant Melanoma" Cancers 13, no. 15: 3907. https://doi.org/10.3390/cancers13153907