Checkpoint-blocker-induced autoimmunity is associated with favourable outcome in metastatic melanoma and distinct T-cell expression profiles
Watson, R. A.
Cheung, V. T. F.
Morgan, Robert David
Taylor, C. A.
Matin, R. N.
Middleton, M. R.
Sacco, J. J.
Payne, M. J.
Fairfax, B. P.
AffiliationOxford University Clinical Academic Graduate School, University of Oxford, Oxford
MetadataShow full item record
AbstractBackground: Immune checkpoint blockers (ICBs) activate CD8+ T cells, eliciting both anti-cancer activity and immune-related adverse events (irAEs). The relationship of irAEs with baseline parameters and clinical outcome is unclear. Methods: Retrospective evaluation of irAEs on survival was performed across primary (N = 144) and secondary (N = 211) independent cohorts of patients with metastatic melanoma receiving single agent (pembrolizumab/nivolumab-sICB) or combination (nivolumab and ipilimumab-cICB) checkpoint blockade. RNA from pre-treatment and post-treatment CD8+ T cells was sequenced and differential gene expression according to irAE development assessed. Results: 58.3% of patients developed early irAEs and this was associated with longer progression-free (PFS) and overall survival (OS) across both cohorts (log-rank test, OS: P < 0.0001). Median survival for patients without irAEs was 16.6 months (95% CI: 10.9-33.4) versus not-reached (P = 2.8 × 10-6). Pre-treatment monocyte and neutrophil counts, but not BMI, were additional predictors of clinical outcome. Differential expression of numerous gene pathway members was observed in CD8+ T cells according to irAE development, and patients not developing irAEs demonstrating upregulated CXCR1 pre- and post-treatment. Conclusions: Early irAE development post-ICB is associated with favourable survival in MM. Development of irAEs is coupled to expression of numerous gene pathways, suggesting irAE development in-part reflects baseline immune activation.
CitationYe W, Olsson-Brown A, Watson RA, Cheung VTF, Morgan RD, Nassiri I, et al. Checkpoint-blocker-induced autoimmunity is associated with favourable outcome in metastatic melanoma and distinct T-cell expression profiles. Br J Cancer. 2021.
JournalBritish Journal of Cancer
- Association between immune-related side effects and efficacy and benefit of immune checkpoint inhibitors - A systematic review and meta-analysis.
- Authors: Hussaini S, Chehade R, Boldt RG, Raphael J, Blanchette P, Maleki Vareki S, Fernandes R
- Issue date: 2021 Jan
- Anti-PD1-Induced Immune-Related Adverse Events and Survival Outcomes in Advanced Melanoma.
- Authors: Suo A, Chan Y, Beaulieu C, Kong S, Cheung WY, Monzon JG, Smylie M, Walker J, Morris D, Cheng T
- Issue date: 2020 May
- Correlation between immune-related adverse events and prognosis in patients with gastric cancer treated with nivolumab.
- Authors: Masuda K, Shoji H, Nagashima K, Yamamoto S, Ishikawa M, Imazeki H, Aoki M, Miyamoto T, Hirano H, Honma Y, Iwasa S, Okita N, Takashima A, Kato K, Boku N
- Issue date: 2019 Oct 21
- Multisystem Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors for Treatment of Non-Small Cell Lung Cancer.
- Authors: Shankar B, Zhang J, Naqash AR, Forde PM, Feliciano JL, Marrone KA, Ettinger DS, Hann CL, Brahmer JR, Ricciuti B, Owen D, Toi Y, Walker P, Otterson GA, Patel SH, Sugawara S, Naidoo J
- Issue date: 2020 Dec 1
- Association of Immune-Related Adverse Events with Clinical Benefit in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Nivolumab.
- Authors: Toi Y, Sugawara S, Kawashima Y, Aiba T, Kawana S, Saito R, Tsurumi K, Suzuki K, Shimizu H, Sugisaka J, Ono H, Domeki Y, Terayama K, Nakamura A, Yamanda S, Kimura Y, Honda Y
- Issue date: 2018 Nov