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

doi:10.1038/s41467-022-29539-3

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

Nat Commun. 2022 Apr 12;13(1):1970. doi: 10.1038/s41467-022-29539-3.

Authors

Sang T Kim^#¹, Yanshuo Chu^#², Mercy Misoi³, Maria E Suarez-Almazor¹, Jean H Tayar¹, Huifang Lu¹, Maryam Buni¹, Jordan Kramer^{4

5}, Emma Rodriguez⁶, Zulekha Hussain¹, Sattva S Neelapu⁷, Jennifer Wang⁸, Amishi Y Shah⁸, Nizar M Tannir⁸, Matthew T Campbell⁸, Don L Gibbons⁹, Tina Cascone⁹, Charles Lu⁹, George R Blumenschein⁹, Mehmet Altan⁹, Bora Lim¹⁰, Vincente Valero¹⁰, Monica E Loghin¹¹, Janet Tu¹², Shannon N Westin¹³, Aung Naing¹⁴, Guillermo Garcia-Manero¹⁵, Noha Abdel-Wahab^{1

16

17}, Hussein A Tawbi¹⁶, Patrick Hwu^{16

18}, Isabella C Glitza Oliva¹⁶, Michael A Davies¹⁶, Sapna P Patel¹⁶, Jun Zou¹⁹, Andrew Futreal², Adi Diab¹⁶, Linghua Wang^{20

21}, Roza Nurieva^{22

23}

Affiliations

¹ Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
² Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
³ Department of General Internal Medicine, Baylor College of Medicine, Houston, TX, 77030, USA.
⁴ Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
⁵ Department of Biology, Georgetown University, Washington, DC, 20057, USA.
⁶ Department of Infectious Disease, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
⁷ Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
⁸ Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
⁹ Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
¹⁰ Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
¹¹ Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
¹² Department of General Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
¹³ Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
¹⁴ Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
¹⁵ Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
¹⁶ Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
¹⁷ Department of Rheumatology and Rehabilitation, Assiut University Hospitals, Faculty of Medicine, Assiut University, El Fateh, Egypt.
¹⁸ H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.
¹⁹ Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
²⁰ Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. lwang22@mdanderson.org.
²¹ The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences (GSBS), Houston, TX, 77030, USA. lwang22@mdanderson.org.
²² Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. rnurieva@mdandesron.org.
²³ The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences (GSBS), Houston, TX, 77030, USA. rnurieva@mdandesron.org.

^# Contributed equally.

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. 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.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Arthritis* / chemically induced
Arthritis* / drug therapy
CD8-Positive T-Lymphocytes
Humans
Immune Checkpoint Inhibitors / adverse effects
Immunotherapy / adverse effects
Neoplasms* / drug therapy
Neoplasms* / etiology

Substances

Immune Checkpoint Inhibitors

Abstract

Publication types

MeSH terms

Substances

Grants and funding