Distinct molecular and immune hallmarks of inflammatory arthritis induced by immune checkpoint inhibitors for cancer therapy

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-...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9005525/
https://www.ncbi.nlm.nih.gov/pubmed/35413951
http://dx.doi.org/10.1038/s41467-022-29539-3
Descripción
Sumario: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. CX3CR1(hi) CD8(+) T cells in blood and CXCR3(hi) CD8(+) T cells in synovial fluid, the most clonally expanded T cells, significantly share TCR repertoires. The migration of blood CX3CR1(hi) 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.

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