Oral Presentation ESA-SRB 2023 in conjunction with ENSA

Immune cell representations following immune checkpoint blockade in patients experiencing thyroid irAEs (#170)

Christopher A Muir 1 2 , Thomas Ashhurst 3 , Venessa HM Tsang 2 4 , Alexander M Menzies 2 5 6 , Roderick J Clifton-Bligh 2 4 7 , Georgina Long 2 6 , Richard Scolyer 2 , Mainthan Palendira 3
  1. St. Vincent's Hospital, Darlinghurst, NSW, Australia
  2. Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia
  3. Charles Perkins Centre, University of Sydney, Camperdown, NSW, Australia
  4. Endocrinology, Royal North Shore Hospital, St. Leonard's, NSW, Australia
  5. Medical Oncology, Royal North Shore Hospital, St. Leonard's, NSW, Australia
  6. Medical Oncology, Melanoma Institute Australia, Wollstonecraft, NSW, Australia
  7. Cancer Genetics, Kolling Institute of Medical Research, St. Leonard's, NSW, Australia

Background: Thyroid immune related adverse events (irAEs) are a frequent side effect of immune checkpoint inhibitor (ICI)-treatment and often result in permanent hypothyroidism requiring lifelong thyroid hormone replacement. Despite the frequency of thyroid-irAEs and their prognostic importance, pathogenic mechanisms driving onset remain incompletely characterized.

Aims: To compare immune cell subpopulations in ICI-treated patients with thyroid-irAEs to those without thyroid-irAEs.

Methods: Using mass cytometric analysis, we studied immune cell populations in peripheral blood samples from patients receiving ICI-treatment for melanoma. Samples were collected at baseline (prior to ICI-treatment) and at the time of a thyroid-irAE (or at a matched timepoint for control group patients) to define the composition of circulating immune cells and associated ICI-treatment induced changes.

Results: Ten patients were enrolled in the study (7 ‘thyroid-irAE’ and 3 ‘control’ patients). Initial unsupervised FlowSOM clustering identified 40 meta-clusters representing cell populations within the major innate and adaptive immune compartments. Differences in circulating immune cells were present at baseline between the two groups. As a percentage of total cells, B-lymphocytes were higher in thyroid-irAE group patients (median 9%, range 7-13) compared with control patients (median 4%, range 4-6; p=0.02). Conversely, NK-cells were lower in thyroid-irAE group patients (median 22%, range 8-24) compared with control group patients (median 38%, range 27-40; p=0.02). As a percentage of total cells at baseline, CD4+ T-cells, CD8+ T-cells, monocytes, and gdT-cells were not different between groups. Furthermore, thyroid-irAE patients experienced significant ICI-treatment related alterations in the composition of circulating cells, whereas no ICI-treatment related changes were observed in any cell lineage in control group (no thyroid-irAE) patients.

Conclusions: Significant differences in the composition of immune cells exist between ICI-treated patients with thyroid-irAEs and those without. Further study is required to determine whether differences have relevance as biomarkers of thyroid irAE susceptibility.