Background: Up to 60% of patients treated with cancer immunotherapy develop severe or life threatening immune-related adverse events (irAEs). Immunosuppression with high doses of corticosteroids or, in refractory cases, with tumor necrosis factor (TNF) antagonists, are the mainstay of treatment for irAEs. It is currently unknown what is the impact of corticosteroids and anti-TNF on the activity of antitumor T-cells. Methods: The influence of clinically relevant doses of dexamethasone (corresponding to an oral dose of 10 to 125 mg prednisolone) and infliximab (anti-TNF) on the activation and killing capacity of tumor-infiltrating lymphocytes (TILs) was tested in vitro. Results: Overall, dexamethasone at low or intermediate/high dose impaired the activation (respectively -46% and -62% in n=8) and tumor-killing ability (respectively -48% and -53% in n=6) of tumor-specific TILs. In contrast, a standard clinical dose of infliximab only had a minor effect on T-cell activation and tumor killing (respectively -20% in n=8 and -10% in n=6). A brief resting following exposure to dexamethasone was sufficient to rescue the in vitro activity of TILs. Conclusions: Clinically relevant doses of infliximab only influenced to a lesser extent the activity of tumor-specific TILs in vitro, whereas even low doses of corticosteroids markedly impaired the antitumor activity of TILs. These data support steroid-sparing strategies and early initiation of anti-TNF for the treatment of irAEs in immuno-oncology.
Citation Format: Marco Donia, Troels H. Borch, Haja D. Radic, Christopher Chamberlain, Aishwarya Gokuldass, Inge Marie Stentoft Svane, Arianna Draghi. Differential effects of corticosteroids and anti-TNF on tumor-specific immune responses— Implications for the management of irAEs [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B154.