Cytokine changes during immune-related adverse events and corticosteroid treatment in melanoma patients receiving immune checkpoint inhibitors
- 31 July 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cancer Immunology, Immunotherapy
- Vol. 70 (8), 2209-2221
- https://doi.org/10.1007/s00262-021-02855-1
Abstract
Background Immune checkpoint inhibitors (ICIs) often cause immune-related adverse events (irAEs), most of which are treated with corticosteroids despite evidence suggesting that corticosteroids may blunt antitumor efficacy. We sought to identify cytokine changes that correlate with irAEs and study the impact of corticosteroid treatment on cytokine levels. Methods We analyzed expression of 34 cytokines in 52 melanoma patients who developed irAEs during therapy with ICIs. Luminex serum assay was performed at baseline, 1, 2, and 3 months after starting ICI. Baseline cytokine levels and longitudinal log(2) fold-change was compared with incidence and grade of irAEs. Cytokine patterns were compared between patients based on development of irAEs and steroid treatment. Results There were no differences in baseline cytokine levels between patients who developed grade 1-2 irAEs (N = 28) vs. grade 3-4 irAEs (N = 24). Dermatitis patients (N = 8) had significantly higher baseline Ang-1 (p = 0.006) and CD40L (p = 0.005). Pneumonitis patients (N = 4) had significantly higher baseline IL-17 (p = 0.009). Colitis patients (N = 8) had a trend toward decreased GCSF (p = 0.08). Through Spearman's correlation analysis, patients who developed irAEs without receiving corticosteroids (N = 23) exhibited harmonization of cytokine fold-change, with 0/276 pairwise comparisons demonstrating significant divergence. In contrast, corticosteroid treatment in patients with irAEs (N = 15) altered fold-change to a discordant pattern (42/276 diverged, 15.2%). This discordant cytokine pattern in patients receiving corticosteroids is similar to the cytokine pattern in patients who did not develop irAEs (N = 8) during the longitudinal profiling period (41/276, 14.9%). Conclusions Baseline levels of certain cytokines correlate with specific irAEs in melanoma patients receiving ICIs. irAEs drive a concordant pattern of cytokine fold-change, which is disrupted by corticosteroid treatment.Funding Information
- Parker Institute for Cancer Immunotherapy (5812101)
This publication has 57 references indexed in Scilit:
- Baseline circulating IL-17 predicts toxicity while TGF-β1 and IL-10 are prognostic of relapse in ipilimumab neoadjuvant therapy of melanomaJournal for ImmunoTherapy of Cancer, 2015
- Immune Checkpoint InhibitorsJAMA Oncology, 2015
- Keratinocytic Vascular Endothelial Growth Factor as a Novel Biomarker for Pathological Skin ConditionBiomolecules & Therapeutics, 2015
- Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patientsNature, 2014
- Management of Immune-Related Adverse Events and Kinetics of Response With IpilimumabJournal of Clinical Oncology, 2012
- Toll‐like receptor 6 drives interleukin‐17A expression during experimental hypersensitivity pneumonitisImmunology, 2010
- New treatment options in the management of IBD – focus on colony stimulating factorsBiologics: Targets and Therapy, 2008
- The Progression of Inflammation Parallels the Dermal Angiogenesis in a Keratin 14 IL‐4‐Transgenic Model of Atopic DermatitisMicrocirculation, 2008
- In situ Expression of CD40 and CD40 Ligand in PsoriasisDermatology, 2004
- Altered Expression of Angiopoietins and Tie2 Endothelium Receptor in PsoriasisJournal of Investigative Dermatology, 2001