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

Sang T. Kim, Yanshuo Chu, Mercy Misoi, Maria E. Suarez-Almazor, Jean H. Tayar, Huifang Lu, Maryam Buni, Jordan Kramer, Emma Rodriguez, Zulekha Hussain, Sattva S. Neelapu, Jennifer Wang, Amishi Y. Shah, Nizar M. Tannir, Matthew T. Campbell, Don L. Gibbons, Tina Cascone, Charles Lu, George R. Blumenschein, Mehmet Altan, Bora Lim, Vincente Valero, Monica E. Loghin, Janet Tu, Shannon N. Westin, Aung Naing, Guillermo Garcia-Manero, Noha Abdel-Wahab, Hussein A. Tawbi, Patrick Hwu, Isabella C. Glitza Oliva, Michael A. Davies, Sapna P. Patel, Jun Zou, Andrew Futreal, Adi Diab, Linghua Wang () and Roza Nurieva ()
Additional contact information
Sang T. Kim: The University of Texas MD Anderson Cancer Center
Yanshuo Chu: The University of Texas MD Anderson Cancer Center
Mercy Misoi: Baylor College of Medicine
Maria E. Suarez-Almazor: The University of Texas MD Anderson Cancer Center
Jean H. Tayar: The University of Texas MD Anderson Cancer Center
Huifang Lu: The University of Texas MD Anderson Cancer Center
Maryam Buni: The University of Texas MD Anderson Cancer Center
Jordan Kramer: The University of Texas MD Anderson Cancer Center
Emma Rodriguez: The University of Texas MD Anderson Cancer Center
Zulekha Hussain: The University of Texas MD Anderson Cancer Center
Sattva S. Neelapu: The University of Texas MD Anderson Cancer Center
Jennifer Wang: The University of Texas MD Anderson Cancer Center
Amishi Y. Shah: The University of Texas MD Anderson Cancer Center
Nizar M. Tannir: The University of Texas MD Anderson Cancer Center
Matthew T. Campbell: The University of Texas MD Anderson Cancer Center
Don L. Gibbons: The University of Texas MD Anderson Cancer Center
Tina Cascone: The University of Texas MD Anderson Cancer Center
Charles Lu: The University of Texas MD Anderson Cancer Center
George R. Blumenschein: The University of Texas MD Anderson Cancer Center
Mehmet Altan: The University of Texas MD Anderson Cancer Center
Bora Lim: The University of Texas MD Anderson Cancer Center
Vincente Valero: The University of Texas MD Anderson Cancer Center
Monica E. Loghin: The University of Texas MD Anderson Cancer Center
Janet Tu: The University of Texas MD Anderson Cancer Center
Shannon N. Westin: The University of Texas MD Anderson Cancer Center
Aung Naing: The University of Texas MD Anderson Cancer Center
Guillermo Garcia-Manero: The University of Texas MD Anderson Cancer Center
Noha Abdel-Wahab: The University of Texas MD Anderson Cancer Center
Hussein A. Tawbi: The University of Texas MD Anderson Cancer Center
Patrick Hwu: The University of Texas MD Anderson Cancer Center
Isabella C. Glitza Oliva: The University of Texas MD Anderson Cancer Center
Michael A. Davies: The University of Texas MD Anderson Cancer Center
Sapna P. Patel: The University of Texas MD Anderson Cancer Center
Jun Zou: The University of Texas MD Anderson Cancer Center
Andrew Futreal: The University of Texas MD Anderson Cancer Center
Adi Diab: The University of Texas MD Anderson Cancer Center
Linghua Wang: The University of Texas MD Anderson Cancer Center
Roza Nurieva: The University of Texas MD Anderson Cancer Center

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-29539-3

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