Immunologic Profiling of Immune-Related Cutaneous Adverse Events with Checkpoint Inhibitors Reveals Polarized Actionable Pathways.
Clin Cancer Res
; 30(13): 2822-2834, 2024 Jul 01.
Article
en En
| MEDLINE
| ID: mdl-38652814
ABSTRACT
PURPOSE:
Immune-related cutaneous adverse events (ircAE) occur in ≥50% of patients treated with checkpoint inhibitors, but the underlying mechanisms for ircAEs are poorly understood. EXPERIMENTALDESIGN:
Phenotyping/biomarker analyses were conducted in 200 patients on checkpoint inhibitors [139 with ircAEs and 61 without (control group)] to characterize their clinical presentation and immunologic endotypes. Cytokines were evaluated in skin biopsies, skin tape strip extracts, and plasma using real-time PCR and Meso Scale Discovery multiplex cytokine assays.RESULTS:
Eight ircAE phenotypes were identified pruritus (26%), maculopapular rash (MPR; 21%), eczema (19%), lichenoid (11%), urticaria (8%), psoriasiform (6%), vitiligo (5%), and bullous dermatitis (4%). All phenotypes showed skin lymphocyte and eosinophil infiltrates. Skin biopsy PCR revealed the highest increase in IFNγ mRNA in patients with lichenoid (P < 0.0001) and psoriasiform dermatitis (P < 0.01) as compared with patients without ircAEs, whereas the highest IL13 mRNA levels were detected in patients with eczema (P < 0.0001, compared with control). IL17A mRNA was selectively increased in psoriasiform (P < 0.001), lichenoid (P < 0.0001), bullous dermatitis (P < 0.05), and MPR (P < 0.001) compared with control. Distinct cytokine profiles were confirmed in skin tape strip and plasma. Analysis determined increased skin/plasma IL4 cytokine in pruritus, skin IL13 in eczema, plasma IL5 and IL31 in eczema and urticaria, and mixed-cytokine pathways in MPR. Broad inhibition via corticosteroids or type 2 cytokine-targeted inhibition resulted in clinical benefit in these ircAEs. In contrast, significant skin upregulation of type 1/type 17 pathways was found in psoriasiform, lichenoid, bullous dermatitis, and type 1 activation in vitiligo.CONCLUSIONS:
Distinct immunologic ircAE endotypes suggest actionable targets for precision medicine-based interventions.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Citocinas
/
Inhibidores de Puntos de Control Inmunológico
Límite:
Aged80
Idioma:
En
Revista:
Clin Cancer Res
Asunto de la revista:
NEOPLASIAS
Año:
2024
Tipo del documento:
Article