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Review
. 2019 Jul 31:10:1818.
doi: 10.3389/fimmu.2019.01818. eCollection 2019.

The TNF Paradox in Cancer Progression and Immunotherapy

Anne Montfort  1 , Céline Colacios  1   2 , Thierry Levade  1   2   3 , Nathalie Andrieu-Abadie  1 , Nicolas Meyer  1   2   4 , Bruno Ségui  1   2
Affiliations
Review

The TNF Paradox in Cancer Progression and Immunotherapy

Anne Montfort et al. Front Immunol. .

Erratum in

No abstract available

Keywords: CTLA-4; PD-1; immune escape; melanoma; tumor necrosis factor (TNF).

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Figures

Figure 1
Figure 1
Role of TNF in cancer-associated immune responses: from tumor necrosis to resistance to immunotherapies and tumor progression. Recombinant TNF, administered by isolated limb perfusion, potently triggers endothelial cell death, and consequently, tumor necrosis. Immune checkpoint blockers promote an acute TNF production in the tumor microenvironment, which contributes to (i) the immune-related adverse events, (ii) the expression of the immunosuppressive molecules PD-L1 and TIM-3 on tumor-infiltrating leukocytes and/or cancer cells, (iii) the activation-induced cell death (AICD) process in CD8+ TILs. Adoptive T cell transfer of CD8 T cells is also associated with TNF production, which leads to melanoma dedifferentiation as well as expression of the CD73 ectonucleotidase. TNF-dependent expression of immunosuppressive molecules in the tumor microenvironment as well as AICD of CD8+ TILs and dedifferentiation of cancer cells favor acquired resistance to immunotherapies. During chronic inflammation, TNF likely contributes to immune escape and tumor progression by facilitating the biological activity and/or expansion of immunosuppressive cells such as regulatory T cells (Tregs), regulatory B cells (Bregs), and myeloid-derived suppressor cells (MDSCs).
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