Nature Communications (Apr 2022)
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,
- Roza Nurieva
Affiliations
- Sang T. Kim
- Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center
- Yanshuo Chu
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center
- Mercy Misoi
- Department of General Internal Medicine, Baylor College of Medicine
- Maria E. Suarez-Almazor
- Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center
- Jean H. Tayar
- Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center
- Huifang Lu
- Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center
- Maryam Buni
- Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center
- Jordan Kramer
- Department of Immunology, The University of Texas MD Anderson Cancer Center
- Emma Rodriguez
- Department of Infectious Disease, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center
- Zulekha Hussain
- Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center
- Sattva S. Neelapu
- Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center
- Jennifer Wang
- Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center
- Amishi Y. Shah
- Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center
- Nizar M. Tannir
- Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center
- Matthew T. Campbell
- Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center
- Don L. Gibbons
- Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center
- Tina Cascone
- Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center
- Charles Lu
- Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center
- George R. Blumenschein
- Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center
- Mehmet Altan
- Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center
- Bora Lim
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center
- Vincente Valero
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center
- Monica E. Loghin
- Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center
- Janet Tu
- Department of General Oncology, The University of Texas MD Anderson Cancer Center
- Shannon N. Westin
- Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center
- Aung Naing
- Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center
- Guillermo Garcia-Manero
- Department of Leukemia, The University of Texas MD Anderson Cancer Center
- Noha Abdel-Wahab
- Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center
- Hussein A. Tawbi
- Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center
- Patrick Hwu
- Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center
- Isabella C. Glitza Oliva
- Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center
- Michael A. Davies
- Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center
- Sapna P. Patel
- Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center
- Jun Zou
- Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center
- Andrew Futreal
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center
- Adi Diab
- Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center
- Linghua Wang
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center
- Roza Nurieva
- Department of Immunology, The University of Texas MD Anderson Cancer Center
- DOI
- https://doi.org/10.1038/s41467-022-29539-3
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 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.
