Investigation of NEW B cell subgroups in malignant melanoma cases.

Determining predictive bio-markers is beneficial for selecting and monitoring the effect of immune checkpoint inhibitor (ICI) treatment in malignant melanoma patients. Although the main target of ICI in malignant melanoma is T cell effector functions, it is suggested that mature and differentiated B cell phenotypes also have a positive relationship with ICI response. However, there are few studies in this context have been conducted. This longitudinal study aimed to investigate the B cell-related immune responses to ICI therapy in metastatic melanoma (MM) patients, differences of B cell subgroups between responding and non-responding MM patients regarding their state of response to ICI treatment, the potential utilization of B cell-related cytokines as prognostic and predictive clinical bio-markers to immunotherapy. Peripheral blood samples were taken from MM patients and healthy donors and B cell subsets were analysed by flow cytometry. BAFF and APRIL serum levels were detected by Elisa in same groups. While ICI treatment increased naive B cell frequency in non-responders, switched memory (IgD-CD27+), classical (CD21+CD27+), unswitched memory B cell and IgA+ B cell frequencies were decreased. Switched (IgM-IgD-) and switched memory B cell frequency were elevated in responders at early and late visits. During ICI treatment, CD21-/lo switched B cell frequencies were increased in NR patients, BAFF-R expression was decreased in R patients. Responders had higher expression of BAFF-R and TACI than non-responders at all visits. At the initiation of ICI therapy, BAFF serum concentrations were detected to be significantly higher in non-responders compared to responders and healthy controls. Results of the thesis suggest that serum levels of BAFF, BAFF-R and TACI expressions and CD21-/lo B cell frequencies can have a role in effective anti-tumour responses in MM cases under immunotherapy.