Immune checkpoint blockades have received significant clinical efficacy in the past decade in many malignancies. However, both primary and acquired resistance becomes one of the major obstacles that cannot be ignored, which seriously limits its clinical efficacy. To predict immunotherapy efficacy remains challenging. Dynamic changes in the systemic immune signature in response to multiple infusions of anti-PD-1antibody are poorly understood.
We collected whole blood samples from cancer patients before and after every cycle anti-PD-1 infusion and isolated PBMCs using Ficoll gradient centrifugation. PBMCs were stained for mass cytometry analyses, and the data were acquired on a CyTOF 2 Helios (Fluidigm). We evaluated tumour responses using Response Evaluation Criteria in Solid Tumours, version 1.1 (RECIST v1.1) by computed tomography (CT). In addition, we conducted animal experiments to verify our experimental results.
We revealed a marked increase in the percentage of CXCR3+ CD4+ CD8- T cells in blood from cancer patients after the first pembrolizumab infusion. Intriguingly, the percentage went down after the second infusion in responding patients. Interestingly, a continuous high percentage of CXCR3+ CD4+ CD8- T cells was observed from patients with progressing disease, while a low percentage with stable disease or partial response confirmed by conventional flow cytometry. Furthermore, depletion of CXCR3+ cells abolished the improvement of melanoma by anti-PD-1 treatment in mice.
The dynamic changes in CXCR3+ CD4+ CD8- T cells in blood could be a prognostic factor and a continuous high percentage of CXCR3+ CD4+ CD8- T cells may reflect resistance to anti-PD-1 therapy.
Clinical trial identification
Legal entity responsible for the study
The First Affiliated Hospital of Nanjing Medical University.
National Natural Science Foundation of China Jiangsu Province Key Medical Talents.
All authors have declared no conflicts of interest.