JEM: selective inhibition of low affinity memory CD8 + T cells by early corticosteroid administration

November 10, 2019 / BIOON / - -- in the past decade, immune checkpoint blockade (ICB) has shown significant effectiveness in the treatment of multiple advanced cancers However, ICB treatment is often complicated by immune related adverse events (iraes), which may be life-threatening if not treated Treatment of Irae may require systemic immunosuppressive drugs, such as corticosteroids, which may run the risk of inhibiting the antitumor effects of ICB However, recent clinical literature has shown that short-term use of systemic corticosteroids may not have a significant effect on the antitumor effect, but there are few studies on its mechanism To solve these problems, in a new study, Tokunaga et al Studied the effect of corticosteroids on mouse melanoma models treated with ICB targeting CTLA-4 or PD-L1 at different time points They determined that early corticosteroid administration, rather than later, can lead to tumor regeneration, suggesting that early corticosteroid administration inhibits memory CD8 + T cells associated with persistent antitumor response Picture from Journal of experimental medicine, 2019, DOI: 10.1084/jem.20190738 Further studies showed that ICB enhanced the new antigen specific CD8 + T cell response with high affinity Systemic corticosteroid administration did not affect these high affinity responses, but decreased the low affinity memory T cell responses in a time-dependent manner Next, the authors studied whether corticosteroid administration affected response in a cohort of patients with metastatic melanoma treated with ipilimumab The authors did not find a significant difference in survival whether the patients were treated with corticosteroids at 16 or 7 weeks Further subset analysis showed that patients with lower mutation load who received steroid treatment earlier had poor prognosis, while the choice of treatment time did not seem to be important for patients with higher mutation load In view of the fact that the single drug treatment of epimab is no longer the standard treatment for advanced melanoma, it is necessary to carry out extensive human research on the current ICB treatment scheme This study highlights the importance of further understanding the mechanism of ICB promoting antitumor response and identifying alternative methods to inhibit Irae while still maintaining the therapeutic effect of ICB An important reminder is that only female mice are used in all experiments, while the gender of human patients is unknown In order to confirm these findings and determine the optimal administration time and dose of immunosuppressive drugs to minimize Irae and maximize anti-tumor response, larger preclinical studies on two genders of mice are needed, treatment options (including combination of immunosuppressive checkpoint inhibitors) are expanded, and clinical studies on gender specific patient cohorts are carried out (bio Com) reference: 1 Akihiro Tokunaga et al Selective initiation of low affinity memory CD8 + T cells by corticosteroids Journal of experimental medicine, 2019, DOI: 10.1084/jem.20190738 2 Rajan P Kulkarni Later is better: Corticosteroids selectively suppress early memory T cells Science Translational Medicine, 2019, doi:10.1126/scitranslmed.aaz3711.