The advent of immune checkpoint blockers such as Pembrolizumab (anti-PD-1) has transformed melanoma treatment by blocking PD-1 on the activated T cells, improving overall survival, progression free survival and overall response rates. However, some metastatic melanoma patients do not have a durable response and can present with upfront primary or longer-term secondary resistance to anti-PD1 immunotherapy.
Chemokines are a family of small cytokines that induce the migration of cells through interactions with their transmembrane receptors. Recently it has been shown that various types of cancer cells express chemokine receptors and the chemokines may play a role in cancer progression. CXCR6 is considered to be an inflammatory chemokine receptor, which can guide effector T cells to sites of inflammation.
The aim of this study was develop a peripheral blood immune profile to monitor the CD4 and CD8 T cell populations, which when combined with RECIST score, reflects the response to pembrolizumab.
Whole blood, sequentially collected, at every treatment cycle for up to 12 months from 16 metastatic melanoma patients receiving Pembrolizumab at the Calvary Mater Hospital, Newcastle. The following markers were assessed by flow cytometry on a BD Biosciences Fortessa II: CD3, CD4, CD8, CD45, CD45RA, FoxP3, IL-9, HLA-DR, CD25, CD274, CD38, CXCR6 and PD-1. Number of cycles received per patient ranged from 2 to 26 with a medium of 19 cycles of pembrolizumab at the commencement of blood collection. Patients with confirmed relapse during the 12 months of blood collection all presented with CXCR6 on CD8+ T cells and disease progression was confirmed by iRECIST.
The results of this study indicate blood immune profiles can be further developed as real-time biomarkers of anti-PD1 resistance, leading to the outcome of detecting resistance and earlier consideration other treatment options for patients that do not respond to anti-PD1 immunotherapy.