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

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^*

^*Corresponding author for this work

University of Texas MD Anderson Cancer Center
Baylor College of Medicine
Georgetown University
Assiut University
Moffitt Cancer Center

Research output: Contribution to journal › Article › peer-review

99 Scopus citations

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.

Original language	English
Article number	1970
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-29539-3
State	Published - Dec 2022
Externally published	Yes

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SDG 3 Good Health and Well-being

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10.1038/s41467-022-29539-3

Cite this

Kim, S. T., Chu, Y., Misoi, M., Suarez-Almazor, M. E., Tayar, J. H., Lu, H., Buni, M., Kramer, J., Rodriguez, E., Hussain, Z., Neelapu, S. S., Wang, J., Shah, A. Y., Tannir, N. M., Campbell, M. T., Gibbons, D. L., Cascone, T., Lu, C., Blumenschein, G. R., ... Nurieva, R. (2022). Distinct molecular and immune hallmarks of inflammatory arthritis induced by immune checkpoint inhibitors for cancer therapy. Nature Communications, 13(1), Article 1970. https://doi.org/10.1038/s41467-022-29539-3

@article{3c61dbf0f9fa4247aa126475d23354f5,

title = "Distinct molecular and immune hallmarks of inflammatory arthritis induced by immune checkpoint inhibitors for cancer therapy",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41467-022-29539-3",

language = "英语",

volume = "13",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

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Kim, ST, Chu, Y, Misoi, M, Suarez-Almazor, ME, Tayar, JH, Lu, H, Buni, M, Kramer, J, Rodriguez, E, Hussain, Z, Neelapu, SS, Wang, J, Shah, AY, Tannir, NM, Campbell, MT, Gibbons, DL, Cascone, T, Lu, C, Blumenschein, GR, Altan, M, Lim, B, Valero, V, Loghin, ME, Tu, J, Westin, SN, Naing, A, Garcia-Manero, G, Abdel-Wahab, N, Tawbi, HA, Hwu, P, Oliva, ICG, Davies, MA, Patel, SP, Zou, J, Futreal, A, Diab, A, Wang, L & Nurieva, R 2022, 'Distinct molecular and immune hallmarks of inflammatory arthritis induced by immune checkpoint inhibitors for cancer therapy', Nature Communications, vol. 13, no. 1, 1970. https://doi.org/10.1038/s41467-022-29539-3

TY - JOUR

T1 - Distinct molecular and immune hallmarks of inflammatory arthritis induced by immune checkpoint inhibitors for cancer therapy

AU - Kim, Sang T.

AU - Chu, Yanshuo

AU - Misoi, Mercy

AU - Suarez-Almazor, Maria E.

AU - Tayar, Jean H.

AU - Lu, Huifang

AU - Buni, Maryam

AU - Kramer, Jordan

AU - Rodriguez, Emma

AU - Hussain, Zulekha

AU - Neelapu, Sattva S.

AU - Wang, Jennifer

AU - Shah, Amishi Y.

AU - Tannir, Nizar M.

AU - Campbell, Matthew T.

AU - Gibbons, Don L.

AU - Cascone, Tina

AU - Lu, Charles

AU - Blumenschein, George R.

AU - Altan, Mehmet

AU - Lim, Bora

AU - Valero, Vincente

AU - Loghin, Monica E.

AU - Tu, Janet

AU - Westin, Shannon N.

AU - Naing, Aung

AU - Garcia-Manero, Guillermo

AU - Abdel-Wahab, Noha

AU - Tawbi, Hussein A.

AU - Hwu, Patrick

AU - Oliva, Isabella C.Glitza

AU - Davies, Michael A.

AU - Patel, Sapna P.

AU - Zou, Jun

AU - Futreal, Andrew

AU - Diab, Adi

AU - Wang, Linghua

AU - Nurieva, Roza

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85128008376

U2 - 10.1038/s41467-022-29539-3

DO - 10.1038/s41467-022-29539-3

M3 - 文章

C2 - 35413951

AN - SCOPUS:85128008376

SN - 2041-1723

VL - 13

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1970

ER -

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

Abstract

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