Abstract
Immune checkpoint inhibitors that target the programmed cell death protein 1 (PD1) pathway have revolutionized the treatment of patients with advanced metastatic melanoma. PD1 inhibitors reinvigorate exhausted tumor-reactive T cells, thus restoring anti-tumor immunity. Tumor necrosis factor alpha (TNFα) is abundantly expressed as a consequence of T cell activation and can have pleiotropic effects on melanoma response and resistance to PD1 inhibitors. In this study, we examined the influence of TNFα on markers of melanoma dedifferentiation, antigen presentation and immune inhibition in a panel of 40 melanoma cell lines. We report that TNFα signaling is retained in all melanomas but the downstream impact of TNFα was dependent on the differentiation status of melanoma cells. We show that TNFα is a poor inducer of antigen presentation molecules HLA-ABC and HLA-DR but readily induces the PD-L2 immune checkpoint in melanoma cells. Our results suggest that TNFα promotes dynamic changes in melanoma cells that may favor immunotherapy resistance.
Original language | English |
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Article number | 605 |
Pages (from-to) | 1-11 |
Number of pages | 11 |
Journal | Biomedicines |
Volume | 9 |
Issue number | 6 |
DOIs | |
Publication status | Published - Jun 2021 |
Bibliographical note
Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.Keywords
- Antigen presentation
- Dedifferentiation
- Immune checkpoint inhibitors
- Immunotherapy