학술논문
Distinct molecular and immune hallmarks of inflammatory arthritis induced by immune checkpoint inhibitors for cancer therapy
Document Type
Original Paper
Author
Kim, Sang T.; Chu, Yanshuo; Misoi, Mercy; Suarez-Almazor, Maria E.; Tayar, Jean H.; Lu, Huifang; Buni, Maryam; Kramer, Jordan; Rodriguez, Emma; Hussain, Zulekha; Neelapu, Sattva S.; Wang, Jennifer; Shah, Amishi Y.; Tannir, Nizar M.; Campbell, Matthew T.; Gibbons, Don L.; Cascone, Tina; Lu, Charles; Blumenschein, George R.; Altan, Mehmet; Lim, Bora; Valero, Vincente; Loghin, Monica E.; Tu, Janet; Westin, Shannon N.; Naing, Aung; Garcia-Manero, Guillermo; Abdel-Wahab, Noha; Tawbi, Hussein A.; Hwu, Patrick; Oliva, Isabella C. Glitza; Davies, Michael A.; Patel, Sapna P.; Zou, Jun; Futreal, Andrew; Diab, Adi; Wang, Linghua; Nurieva, Roza
Source
Nature Communications. 13(1)
Subject
Language
English
ISSN
2041-1723
Abstract
Immune checkpoint inhibitors are associated with immune-related adverse events (irAEs), including arthritis (arthritis-irAE). Management of arthritis-irAE is challenging because immunomodulatory therapy for arthritis should not impede antitumor immunity. Understanding of the mechanisms of arthritis-irAE is critical to overcome this challenge, but the pathophysiology remains unknown. Here, we comprehensively analyze peripheral blood and/or synovial fluid samples from 20 patients with arthritis-irAE, and unmask a prominent Th1-CD8+ T cell axis in both blood and inflamed joints. CX3CR1hi CD8+ T cells in blood and CXCR3hi CD8+ T cells in synovial fluid, the most clonally expanded T cells, significantly share TCR repertoires. The migration of blood CX3CR1hi CD8+ T cells into joints is possibly mediated by CXCL9/10/11/16 expressed by myeloid cells. Furthermore, arthritis after combined CTLA-4 and PD-1 inhibitor therapy preferentially has enhanced Th17 and transient Th1/Th17 cell signatures. Our data provide insights into the mechanisms, predictive biomarkers, and therapeutic targets for arthritis-irAE.
Arthritis is the most common rheumatic immune-related adverse event (irAE) occurring in cancer patients receiving immune checkpoint inhibitors. Here the authors study the immune landscape of blood and synovial fluid samples from patients with arthritis-irAE, reporting immunological differences and similarities with classic autoimmune arthritis.
Arthritis is the most common rheumatic immune-related adverse event (irAE) occurring in cancer patients receiving immune checkpoint inhibitors. Here the authors study the immune landscape of blood and synovial fluid samples from patients with arthritis-irAE, reporting immunological differences and similarities with classic autoimmune arthritis.