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

Cancer Cell, Год журнала: 2025, Номер 43(2), С. 269 - 291.e19

Опубликована: Фев. 1, 2025

Highlights•Drugs currently used against irAEs reduce anti-tumor immunity•ECP induces adiponectin production in inflamed organs while sparing tumor tissue•ECP high response rates patients with ICI-induced irAEsSummaryImmune-related adverse events (irAEs) cancer receiving immune checkpoint inhibitors (ICIs) cause morbidity and necessitate cessation of treatment. Comparing irAE treatments, we find that immunity is preserved mice after extracorporeal photopheresis (ECP) but reduced glucocorticosteroids, TNFα blockade, α4β7-integrin inhibition. Local elicits a tissue-specific effect by reducing pro-inflammatory T cell frequencies the colon tumor-specific development. A prospective phase-1b/2 trial (EudraCT-No.2021-002073-26) 14 reveals low ECP-related toxicity. Overall rate for all 92% (95% confidence interval [CI]: 63.97%–99.81%); colitis-specific complete remission 100% CI: 63.06%–100%). Glucocorticosteroid dosages could be ECP therapy. The ECP-adiponectin axis reduces intestinal tissue-resident memory activation CD4+IFN-γ+ cells colitis without evidence loss immunity. In conclusion, identify as an immunomodulatory molecule controls blocking immunity.Graphical abstract

Язык: Английский

Increased serum NfL and GFAP levels indicate different subtypes of neurologic immune‐related adverse events during treatment with immune checkpoint inhibitors

International Journal of Cancer, Год журнала: 2025, Номер unknown

Опубликована: Янв. 20, 2025

Abstract Neurologic immune‐related adverse events (nirAEs) represent rare, yet severe side effects associated with immune checkpoint inhibitor (ICI) therapy. Given the absence of established diagnostic biomarkers for nirAEs, we aimed to evaluate utility serum Neurofilament Light Chain (NfL) and Glial Fibrillary Acidic Protein (GFAP). Fifty‐three patients were included at three comprehensive cancer centers, these 20 manifest nirAEs 11 irHypophysitis. Controls without any irAE ( n = 8) other irAEs 14). Using a single‐molecule enzyme‐linked immunosorbent assay (Simoa), levels measured prior to, during after manifestation (n)irAEs in 80 samples. Symptom severity was graded according Common Criteria Adverse Events (CTCAE) version 5.0. Serum NfL significantly higher nirAE group 20) compared irHypophysitis 11; p .0025) controls 22; .0384). Subgroup analysis demonstrated significant elevation peripheral nerves (PNirAE) contrast neuromuscular syndromes (NMirAE) .0260). GFAP highest affecting central nervous system (CNSirAE) PNirAE NMirAE .0064). increased .0069, .0092). Individuals elevated exhibited less favorable outcomes .0199). Measurement may be helpful differentiation broad spectrum serve as an indicator symptom severity. Further investigation is needed their potential prognostic biomarkers.

Язык: Английский

Extracorporeal photopheresis effective in immune-related capillary leak/polyserositis in splenectomized patient

European Journal of Cancer, Год журнала: 2024, Номер 216, С. 115189 - 115189

Опубликована: Дек. 18, 2024

Язык: Английский