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Abstract Number: 1571

Distinct T Cell Responses in Inflammatory Arthritis Associated with Combined CTLA-4 and PD-1 Inhibitor Therapy

Sang Kim1, Jean Tayar2, Maria Suarez-Almazor3, Huifang Lu4, Yang-Zhi Zhao5, Margarita Divenko5, William Padron5, Emma Rodriguez5, Sattva Neelapu5, Jennifer Wang5, Amish Shah5, Nizar Tannir5, Don Gibbons5, Guillermo Garcia-Manero5, Hussein Tawbi5, Patrick Hwu5, Andrew Futreal5, Adi Diab5 and Roza Nurieva5, 1The Univesrity of Texas MD Andesron Cancer Center, Pearland, TX, 2The University of Texas, MD Anderson Cancer Center, Houston, TX, 3University of Texas MD Anderson Cancer Center, Houston, TX, 4MD Anderson, Houston, TX, 5MD Anderson, Houston

Meeting: ACR Convergence 2020

Keywords: autoimmune diseases, corticosteroids, immunology, TH17 Cells

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Session Information

Date: Monday, November 9, 2020

Session Title: Immunological Complications of Therapy Poster

Session Type: Poster Session D

Session Time: 9:00AM-11:00AM

Background/Purpose: Despite of unprecedented clinical success in cancer therapeutics, immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs), including arthritis (arthritis-irAE). Arthritis-irAE can not only cause bone erosions but also warrant early termination of ICI treatment. Further, treatment for the arthritis-irAE can mitigate anti-tumor immunity revived by the ICI treatment. To overcome such clinical challenges, understanding the pathophysiology of arthritis-irAE is critical; however, these mechanisms remain unknown.

Methods: We collected and performed immunoprofiling of synovial fluid from seven patients with active arthritis-irAE and three control patients with osteoarthritis. In parallel, we examined the impact of ICIs on collagen induced arthritis (CIA).

Results: Four patients developed arthritis after PD-1 inhibitor monotherapy and three after combination therapy with CTLA-4 and PD-1 inhibitors. Two patients in the combination therapy group required interleukin (IL)-6 receptor inhibitor therapy in addition to steroids, compared with one patient in the monotherapy group (sulfasalazine). IL-17-producing CD4+ T cells (Th17) were enriched in the combination therapy group compared to monotherapy group (1.01±0.73% in live CD4+ T cells in the monotherapy group compared with 3.19±0.31% in the combination therapy group; P=0.005). Synovial fluid levels of IL-6 and IL-17A, key cytokines for Th17 cell differentiation and function, were higher in the combination ICI therapy group than in the monotherapy group, suggesting the role of Th17-related cytokines in disease pathogenesis. Like humans, ICIs, especially in combinations, facilitate the development and progression of CIA. Importantly, although not reached statistical significance, like humans, collagen-specific Th17 cells were enriched in CIA mice receiving combined ICI treatment.

Conclusion: Our data suggests that Th17 cells, especially in post combination ICI therapy, play a critical role in the disease pathogenesis. Comprehensive studies with more patients/controls along with recapitulating mouse models will unmask underlying mechanisms of arthritis-irAE. Further, understanding of altered immunity in the arthritis-irAE will provide insights of inflammatory arthritis secondary to the classical autoimmune diseases.


Disclosure: S. Kim, None; J. Tayar, None; M. Suarez-Almazor, None; H. Lu, None; Y. Zhao, None; M. Divenko, None; W. Padron, None; E. Rodriguez, None; S. Neelapu, None; J. Wang, None; A. Shah, None; N. Tannir, None; D. Gibbons, None; G. Garcia-Manero, None; H. Tawbi, None; P. Hwu, None; A. Futreal, None; A. Diab, None; R. Nurieva, None.

To cite this abstract in AMA style:

Kim S, Tayar J, Suarez-Almazor M, Lu H, Zhao Y, Divenko M, Padron W, Rodriguez E, Neelapu S, Wang J, Shah A, Tannir N, Gibbons D, Garcia-Manero G, Tawbi H, Hwu P, Futreal A, Diab A, Nurieva R. Distinct T Cell Responses in Inflammatory Arthritis Associated with Combined CTLA-4 and PD-1 Inhibitor Therapy [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/distinct-t-cell-responses-in-inflammatory-arthritis-associated-with-combined-ctla-4-and-pd-1-inhibitor-therapy/. Accessed June 25, 2022.
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