Adiponectin reduces immune checkpoint inhibitor-induced inflammation without blocking anti-tumor immunity

被引：0

作者：

Braun, Lukas M. ^{[1
,2
]}

Giesler, Sophie ^{[1
]}

Andrieux, Geoffroy ^{[3
]}

Riemer, Roxane ^{[1
]}

Talvard-Balland, Nana ^{[1
]}

Duquesne, Sandra ^{[1
]}

Rueckert, Tamina ^{[1
,2
]}

Unger, Susanne ^{[4
]}

Kreutmair, Stefanie ^{[1
,4
]}

Zwick, Melissa ^{[1
,2
]}

Follo, Marie ^{[1
]}

Hartmann, Alina ^{[1
]}

Osswald, Natascha ^{[1
]}

Melchinger, Wolfgang ^{[1
]}

Chapman, Stefanie

Hutchinson, James A. ^{[5
]}

Haferkamp, Sebastian ^{[6
]}

Torster, Leopold ^{[7
]}

Koett, Julian ^{[7
]}

Gebhardt, Christoffer ^{[7
]}

Hellwig, Dirk ^{[8
]}

Karantzelis, Nikolaos ^{[1
]}

Wallrabenstein, Till ^{[1
]}

Lowinus, Theresa ^{[1
]}

Yuecel, Mehtap ^{[1
]}

Brehm, Niklas ^{[1
]}

Rawluk, Justyna ^{[1
]}

Pfeifer, Dietmar ^{[1
]}

Bronsert, Peter ^{[9
]}

Rogg, Manuel ^{[9
]}

Mattern, Sven ^{[10
]}

Heikenwaelder, Mathias

Fusco, Stefano ^{[12
]}

Malek, Nisar P. ^{[12
]}

Singer, Stephan ^{[10
,11
]}

Schmitt-Graeff, Annette ^{[13
]}

Ceteci, Fatih ^{[14
]}

Greten, Florian R. ^{[14
]}

Blazar, Bruce R. ^{[15
]}

Boerries, Melanie ^{[3
,16
]}

Koehler, Natalie ^{[1
]}

Duyster, Justus ^{[1
,16
]}

Ihorst, Gabriele ^{[17
]}

Lassmann, Silke ^{[9
]}

Keye, Philip ^{[18
]}

Minguet, Susana ^{[19
]}

Schadendorf, Dirk ^{[20
,21
,22
]}

Ugurel, Selma ^{[20
,21
]}

Rafei-Shamsabadi, David ^{[23
]}

Thimme, Robert ^{[24
]}

机构：

[1] Univ Freiburg, Dept Internal Med 1, Med Ctr Univ Freiburg, Dept Neuroradiol, Freiburg, Germany

[2] Univ Freiburg, Fac Biol, Freiburg, Germany

[3] Univ Freiburg, Inst Med Bioinformat & Syst Med, Med Ctr, Fac Med, Freiburg, Germany

[4] Univ Zurich, Inst Expt Immunol, Zurich, Switzerland

[5] Univ Hosp Regensburg, Dept Surg, Regensburg, Germany

[6] Univ Hosp Regensburg, Dept Dermatol, Regensburg, Germany

[7] Univ Med Ctr Hamburg Eppendorf, Dept Dermatol & Venereol, Hamburg, Germany

[8] Univ Hosp Regensburg, Dept Nucl Med, Regensburg, Germany

[9] Univ Freiburg, Inst Surg Pathol, Fac Med, Med Ctr, Freiburg, Germany

[10] Univ Klinikum, Inst Pathol, D-72076 Tubingen, Germany

[11] Cluster Excellence, Cluster Excellence iFIT EXC Image Guided & Functio, D-72076 Tubingen, Germany

[12] Uniklin Tubingen, Med Klin I, D-38126 Braunschweig, Germany

[13] Univ Freiburg, Freiburg, Germany

[14] Georg Speyer Haus, Inst Tumor Biol & Expt Therapy, Frankfurt, Germany

[15] Univ Minnesota, Dept Pediat, Div Blood & Marrow Transplant & Cellular Therapy, Minneapolis, MN USA

[16] Univ Freiburg, Partnership DKFZ & Med Ctr, German Canc Consortium DKTK, Partner Site Freiburg, Freiburg, Germany

[17] Univ Freiburg, Med Ctr, Fac Med, Clin Trials Unit, Freiburg, Germany

[18] Univ Freiburg, Fac Med, Eye Ctr, Med Ctr, Freiburg, Germany

[19] Univ Freiburg, Signalling Res Ctr BIOSS, Freiburg, Germany

[20] Univ Duisburg Essen, Univ Hosp Essen, Dept Dermatol, Essen, Germany

[21] German Canc Consortium DKTK, Partner Site Essen Duesseldorf, Essen, Germany

[22] Univ Duisburg Essen, Natl Ctr Tumor Dis NCT West, Res Ctr One Hlth, Campus Essen & Res Alliance Ruhr, Essen, Germany

[23] Univ Freiburg, Fac Med, Med Ctr, Dept Dermatol, Freiburg, Germany

[24] Univ Freiburg, Dept Internal Med 2, Med Ctr Univ Freiburg, Dept Neuroradiol, Freiburg, Germany

[25] Univ Freiburg, Signalling Res Ctr BIOSS, Freiburg, Germany

[26] Univ Freiburg, CIBSS Ctr Integrat Biol Signalling Studies, Freiburg, Germany

[27] Johns Hopkins Sch Med, Bloomberg Kimmel Inst Canc Immunotherapy, Dept Oncol, Baltimore, MD 21287 USA

[28] Univ Hosp Basel, Fac Med, Dept Biomed, Basel, Switzerland

[29] Univ Basel, Basel, Switzerland

[30] Univ Hosp Basel, Div Hematol, Basel, Switzerland

来源：

CANCER CELL | 2025年 / 43卷 / 02期

关键词：

VERSUS-HOST-DISEASE; EXTRACORPOREAL PHOTOPHERESIS; MACROPHAGE POLARIZATION; INDUCED COLITIS; ADVERSE EVENTS; TNF-ALPHA; CELLS; IPILIMUMAB; MELANOMA; CANCER;

D O I：

10.1016/j.ccell.2025.01.004

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Immune-related adverse events (irAEs) in cancer patients receiving immune checkpoint inhibitors (ICIs) cause morbidity and necessitate cessation of treatment. Comparing irAE treatments, we find that anti-tumor immunity is preserved in mice after extracorporeal photopheresis (ECP) but reduced with glucocorticosteroids, TNFa blockade, and a4b7-integrin inhibition. Local adiponectin production elicits a tissue-specific effect by reducing pro-inflammatory T cell frequencies in the colon while sparing tumor-specific T cell development. A prospective phase-1b/2 trial (EudraCT-No.2021-002073-26) with 14 patients reveals low ECPrelated toxicity. Overall response rate for all irAEs is 92% (95% confidence interval [CI]: 63.97%-99.81%); colitis-specific complete remission rate is 100% (95% CI: 63.06%-100%). Glucocorticosteroid dosages could be reduced for all patients after ECP therapy. The ECP-adiponectin axis reduces intestinal tissue-resident memory T cell activation and CD4+IFN-g+ T cells in patients with ICI-induced colitis without evidence of loss of anti-tumor immunity. In conclusion, we identify adiponectin as an immunomodulatory molecule that controls ICI-induced irAEs without blocking anti-tumor immunity.

引用

页数：43

共 50 条

[41] RORγ agonists regulate immune checkpoint receptors to enhance anti-tumor immunity
Hu, Xiao
Liu, Xikui
Moisan, Jacques
Paulos, Chrystal
Wang, Yahong
Spooner, Chauncey
Lesch, Charles
Morgan, Rodney
Mertz, David
Bousley, Dick
Taylor, Clarke
Van Huis, Chad
Skalitzky, Don
Aicher, Thomas
Toogood, Peter
Carter, Laura
CANCER RESEARCH, 2016, 76
[42] Immune checkpoint inhibitor-induced immune-related AEs
Reactions Weekly, 2024, 2033 (1) : 12 - 12
[43] Immune checkpoint inhibitor-induced colitis: A comprehensive review
Som, Aniruddh
Mandaliya, Rohan
Alsaadi, Dana
Farshidpour, Maham
Charabaty, Aline
Malhotra, Nidhi
Mattar, Mark C.
WORLD JOURNAL OF CLINICAL CASES, 2019, 7 (04) : 405 - 418
[44] Treatment of immune checkpoint inhibitor-induced inflammatory arthritis
Jeurling, Susanna
Cappelli, Laura C.
CURRENT OPINION IN RHEUMATOLOGY, 2020, 32 (03) : 315 - 320
[45] Immune checkpoint inhibitor-induced polyarthritis: a case series
Smith-Uffen, Megan
Tselios, Konstantinos
CANCER IMMUNOLOGY RESEARCH, 2022, 10 (12)
[46] Immune Checkpoint Inhibitor-Induced Colitis in Patients With Malignancy
Chu, Yan
Vaidyan, Philip
AMERICAN JOURNAL OF GASTROENTEROLOGY, 2020, 115 : S939 - S939
[47] Clinicopathological Characteristics of Immune Checkpoint Inhibitor-induced Hepatitis
Parrack, Paige
Shih, Angela
Zucker, Stephen
Li, Michael
Zhao, Lei
LABORATORY INVESTIGATION, 2023, 103 (03) : S1398 - S1400
[48] Immune Checkpoint Inhibitor-Induced Bilateral Phrenic Neuropathy
Anderson, D. K.
Olson, E. J.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2020, 201
[49] IMMUNE CHECKPOINT INHIBITOR-INDUCED FATAL HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS
Fowler, Cosmo
Kumar, Sany
Joseph, Ormena
Shakya, Sabnam
Pastores, Stephen
CRITICAL CARE MEDICINE, 2024, 52
[50] IMMUNE CHECKPOINT INHIBITOR-INDUCED THYROIDITIS: CASE REPORT
Aloyan, T.
Antonov, E.
Salimova, D.
Chandra, G.
ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY, 2024, 133 (06) : S105 - S105

← 1 2 3 4 5 →