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

被引：18

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

页码：269 / 291.e19

页数：43

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