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Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT).
Genta, Sofia; Lajkosz, Katherine; Yee, Noelle R; Spiliopoulou, Pavlina; Heirali, Alya; Hansen, Aaron R; Siu, Lillian L; Saibil, Sam; Stayner, Lee-Anne; Yanekina, Maryia; Sauder, Maxwell B; Keshavarzi, Sareh; Salawu, Abdulazeez; Vornicova, Olga; Butler, Marcus O; Bedard, Philippe L; Razak, Albiruni R Abdul; Rottapel, Robert; Chruscinski, Andrzej; Coburn, Bryan; Spreafico, Anna.
Affiliation
  • Genta S; Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
  • Lajkosz K; Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, ON, Canada.
  • Yee NR; Toronto General Research Institute, University Health Network Toronto, Toronto, ON, Canada.
  • Spiliopoulou P; Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
  • Heirali A; Toronto General Research Institute, University Health Network Toronto, Toronto, ON, Canada.
  • Hansen AR; Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
  • Siu LL; Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
  • Saibil S; Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
  • Stayner LA; Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
  • Yanekina M; Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
  • Sauder MB; Division of Dematology, Department of Medicine, University of Toronto, Toronto, ON, Canada.
  • Keshavarzi S; Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, ON, Canada.
  • Salawu A; Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
  • Vornicova O; Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
  • Butler MO; Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
  • Bedard PL; Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
  • Razak ARA; Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
  • Rottapel R; Department of Immunology, University of Toronto, Toronto, ON, Canada.
  • Chruscinski A; University Health Network, University of Toronto, Toronto, ON, Canada.
  • Coburn B; Toronto General Research Institute, University Health Network Toronto, Toronto, ON, Canada.
  • Spreafico A; Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada. anna.spreafico@uhn.ca.
J Exp Clin Cancer Res ; 42(1): 276, 2023 Oct 21.
Article in En | MEDLINE | ID: mdl-37865776
ABSTRACT

BACKGROUND:

Immune-checkpoint inhibitors (ICI) can lead to immune-related adverse events (irAEs) in a significant proportion of patients. The mechanisms underlying irAEs development are mostly unknown and might involve multiple immune effectors, such as T cells, B cells and autoantibodies (AutoAb).

METHODS:

We used custom autoantigen (AutoAg) microarrays to profile AutoAb related to irAEs in patients receiving ICI. Plasma was collected before and after ICI from cancer patients participating in two clinical trials (NCT03686202, NCT02644369). A one-time collection was obtained from healthy controls for comparison. Custom arrays with 162 autoAg were used to detect IgG and IgM reactivities. Differences of median fluorescent intensity (MFI) were analyzed with Wilcoxon sign rank test and Kruskal-Wallis test. MFI 500 was used as threshold to define autoAb reactivity.

RESULTS:

A total of 114 patients and 14 healthy controls were included in this study. irAEs of grade (G) ≥ 2 occurred in 37/114 patients (32%). We observed a greater number of IgG and IgM reactivities in pre-ICI collections from patients versus healthy controls (62 vs 32 p < 0.001). Patients experiencing irAEs G ≥ 2 demonstrated pre-ICI IgG reactivity to a greater number of AutoAg than patients who did not develop irAEs (39 vs 33 p = 0.040). We observed post-treatment increase of IgM reactivities in subjects experiencing irAEs G ≥ 2 (29 vs 35, p = 0.021) and a decrease of IgG levels after steroids (38 vs 28, p = 0.009).

CONCLUSIONS:

Overall, these results support the potential role of autoAb in irAEs etiology and evolution. A prospective study is ongoing to validate our findings (NCT04107311).
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Autoantigens / Immune Checkpoint Inhibitors Limits: Humans Language: En Journal: J Exp Clin Cancer Res Year: 2023 Document type: Article Affiliation country: Canada
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Autoantigens / Immune Checkpoint Inhibitors Limits: Humans Language: En Journal: J Exp Clin Cancer Res Year: 2023 Document type: Article Affiliation country: Canada