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.

Details

Title
Distinct molecular and immune hallmarks of inflammatory arthritis induced by immune checkpoint inhibitors for cancer therapy
Author
Kim, Sang T. 1   VIAFID ORCID Logo  ; Chu, Yanshuo 2 ; Misoi, Mercy 3 ; Suarez-Almazor, Maria E. 1 ; Tayar, Jean H. 1 ; Lu, Huifang 1 ; Buni, Maryam 1 ; Kramer, Jordan 4 ; Rodriguez, Emma 5 ; Hussain, Zulekha 1 ; Neelapu, Sattva S. 6   VIAFID ORCID Logo  ; Wang, Jennifer 7 ; Shah, Amishi Y. 7   VIAFID ORCID Logo  ; Tannir, Nizar M. 7 ; Campbell, Matthew T. 7   VIAFID ORCID Logo  ; Gibbons, Don L. 8   VIAFID ORCID Logo  ; Cascone, Tina 8   VIAFID ORCID Logo  ; Lu, Charles 8 ; Blumenschein, George R. 8 ; Altan, Mehmet 8 ; Lim, Bora 9 ; Valero, Vincente 9 ; Loghin, Monica E. 10 ; Tu, Janet 11   VIAFID ORCID Logo  ; Westin, Shannon N. 12   VIAFID ORCID Logo  ; Naing, Aung 13   VIAFID ORCID Logo  ; Garcia-Manero, Guillermo 14   VIAFID ORCID Logo  ; Abdel-Wahab, Noha 15 ; Tawbi, Hussein A. 16   VIAFID ORCID Logo  ; Hwu, Patrick 17 ; Oliva, Isabella C. Glitza 16 ; Davies, Michael A. 16   VIAFID ORCID Logo  ; Patel, Sapna P. 16   VIAFID ORCID Logo  ; Zou, Jun 18   VIAFID ORCID Logo  ; Futreal, Andrew 2   VIAFID ORCID Logo  ; Diab, Adi 16 ; Wang, Linghua 19   VIAFID ORCID Logo  ; Nurieva, Roza 20   VIAFID ORCID Logo 

1  The University of Texas MD Anderson Cancer Center, Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
2  The University of Texas MD Anderson Cancer Center, Department of Genomic Medicine, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
3  Baylor College of Medicine, Department of General Internal Medicine, Houston, USA (GRID:grid.39382.33) (ISNI:0000 0001 2160 926X) 
4  The University of Texas MD Anderson Cancer Center, Department of Immunology, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776); Georgetown University, Department of Biology, Washington, USA (GRID:grid.213910.8) (ISNI:0000 0001 1955 1644) 
5  The University of Texas MD Anderson Cancer Center, Department of Infectious Disease, Infection Control and Employee Health, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
6  The University of Texas MD Anderson Cancer Center, Department of Lymphoma and Myeloma, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
7  The University of Texas MD Anderson Cancer Center, Department of Genitourinary Medical Oncology, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
8  The University of Texas MD Anderson Cancer Center, Department of Thoracic Head and Neck Medical Oncology, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
9  The University of Texas MD Anderson Cancer Center, Department of Breast Medical Oncology, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
10  The University of Texas MD Anderson Cancer Center, Department of Neuro-Oncology, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
11  The University of Texas MD Anderson Cancer Center, Department of General Oncology, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
12  The University of Texas MD Anderson Cancer Center, Department of Gynecologic Oncology and Reproductive Medicine, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
13  The University of Texas MD Anderson Cancer Center, Department of Investigational Cancer Therapeutics, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
14  The University of Texas MD Anderson Cancer Center, Department of Leukemia, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
15  The University of Texas MD Anderson Cancer Center, Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776); The University of Texas MD Anderson Cancer Center, Department of Melanoma Medical Oncology, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776); Assiut University, Department of Rheumatology and Rehabilitation, Assiut University Hospitals, Faculty of Medicine, El Fateh, Egypt (GRID:grid.252487.e) (ISNI:0000 0000 8632 679X) 
16  The University of Texas MD Anderson Cancer Center, Department of Melanoma Medical Oncology, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
17  The University of Texas MD Anderson Cancer Center, Department of Melanoma Medical Oncology, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776); H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA (GRID:grid.468198.a) (ISNI:0000 0000 9891 5233) 
18  The University of Texas MD Anderson Cancer Center, Department of Laboratory Medicine, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
19  The University of Texas MD Anderson Cancer Center, Department of Genomic Medicine, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776); The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences (GSBS), Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
20  The University of Texas MD Anderson Cancer Center, Department of Immunology, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776); The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences (GSBS), Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
Pages
1970
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-022-29539-3
ProQuest document ID
2649422715
Copyright
© The Author(s) 2022. corrected publication 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.