TNF in the era of immune checkpoint inhibitors: friend or foe?
Review of clinical and preclinical studies that address the relationship between TNF, TNF inhibition and cancer.
Citation: Chen, A.Y., Wolchok, J.D. & Bass, A.R. TNF in the era of immune checkpoint inhibitors: friend or foe?. Nat Rev Rheumatol 17, 213–223 (2021).
Abstract: Immune checkpoint inhibitors (ICIs) are effective in the treatment of patients with
advanced cancer and have emerged as a pillar of standard cancer care. However, their use is
complicated by adverse effects known as immune-related adverse events (irAEs), including
ICI-induced inflammatory arthritis. ICI-induced inflammatory arthritis is distinguished from other
irAEs by its persistence and requirement for long-term treatment. TNF inhibitors are commonly
used to treat inflammatory diseases such as rheumatoid arthritis, spondyloarthropathies and
inflammatory bowel disease, and have also been adopted as second-line agents to treat irAEs
refractory to glucocorticoid treatment. Experiencing an irAE is associated with a better antitumour
response after ICI treatment. However, whether TNF inhibition can be safely used to treat irAEs
without promoting cancer progression, either by compromising ICI therapy efficacy or via another
route, remains an open question. In this Review, we discuss clinical and preclinical studies that
address the relationship between TNF, TNF inhibition and cancer. The bulk of the evidence suggests
that at least short courses of TNF inhibitors are safe for the treatment of irAEs in patients with
cancer undergoing ICI therapy. Data from preclinical studies hint that TNF inhibition might
augment the antitumour effect of ICI therapy while simultaneously ameliorating irAEs.