45 Characterization of B cell responses during checkpoint inhibitor therapy in Melanoma

Cevhertas Lacin1/2/3, Flatz Lukas4/5/6, Akdis Mübeccel1, van de Veen Willem1/2

  1. Swiss Institute of Allergy and Asthma Research (SIAF), University Zurich, Davos, Switzerland
  2. Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland
  3. Department of Medical Immunology, Institute of Health Sciences, Bursa Uludag University, Bursa, Turkey
  4. Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland
  5. Department of Dermatology and Allergology, Kantonsspital St. Gallen, Switzerland
  6. Department of Oncology and Haematology, Kantonsspital St. Gallen, Switzerland

Background: Malignant melanoma (22%), is one of the most common immune-related tumours and represents a major cause of death from skin cancer. Checkpoint inhibitor (CI) therapy is a form of cancer treatment that can block inhibitory checkpoints, thereby restoring the immune response to tumours. CI therapy increased the progression-free and overall survival of melanoma patients with less severe adverse effects compared to chemotherapy. These immunotherapeutic agents induce the anti-tumour response by reactivating the immune cells and usually cause immune-related side effects. However, the effect of CIs on B cells , which are the source of antibody production, is not fully understood.

Aim: This study is aimed at delineating the role of B cells in CI therapy and their association with a good clinical response as well as the development of toxicity/side-effects of treatment.

Methods: We performed a longitudinal study of patients with advanced melanoma who were treated with three different CIs as monotherapy or combined therapy. We collected blood and isolated lymphocytes from 27 melanoma patients with three different time points; before (Time point 1, T1), one week after start treatment (T2) and at 5th visit (T3). We performed flow cytometric analysis with thirty different cell surface molecules on B cells. This laser-based technology is a method to analyze the expression of cell surface molecules with fluorochrome-conjugated antibodies, which allows detailed phenotyping of individual cells.

Results: Fourteen patients responded and thirteen non-responded to the treatment. Nineteen patients (70%) developed toxicity. B memory cells which have the capacity to remember a foreign substance, reduced frequency after treatment while the naïve-untrained B cells were uprising in blood in all non-responders and also who had side effects. Overall, our data suggest that antibody-producing cell levels change over the course of therapy.