Melanoma cell state-specific responses to TNFα

Su Yin Lim, Sara Alavi, Zizhen Ming, Elena Shklovskaya, Carina Fung, Ashleigh Stewart, Helen Rizos*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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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 languageEnglish
Article number605
Pages (from-to)1-11
Number of pages11
JournalBiomedicines
Volume9
Issue number6
DOIs
Publication statusPublished - 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

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