Immune Checkpoint Programmed Cell Death Protein-1 (PD-1) Expression on Bone Marrow T Cell Subsets in Patients With Plasma Cell Myeloma
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Background: Plasma cell myeloma (PCM) is caused by immune dysregulation. We evaluated the expression of immune checkpoint programmed cell death protein-1 (PD-1) on T cell subsets in PCM patients according to disease course and cytogenetic abnormalities. This study aimed to find a target group suitable for therapeutic use of PD-1 blockade in PCM. Methods: A total of 188 bone marrow (BM) samples from 166 PCM patients and 32 controls were prospectively collected between May 2016 and May 2017. PD-1 expression on BM T cell subsets was measured using flow cytometry. Results: At diagnosis, the median PD-1 expression on CD4+ T cells was 24.6%, which did not significantly differ from that in controls. After stem cell transplantation, PD-1 expression on CD4+ T cells was higher than that at diagnosis (P<0.001), regardless of residual disease. PD-1 expression on CD4+ T cells in patients with residual disease after chemotherapy was significantly higher than that at diagnosis (P=0.001) and after complete remission following chemotherapy (P=0.044). PD-1 expression on CD8+ T cells was higher in PCM patients with cytogenetic abnormalities, including monosomy 13, 1q gain, complex karyotype, and hypodiploidy. Conclusions: PD-1 blockade might have therapeutic potential in refractory PCM patients after chemotherapy, especially in those with high- or intermediate-risk cytogenetic abnormalities.
Abstract
Background: Plasma cell myeloma (PCM) is caused by immune dysregulation. We evaluated the expression of immune checkpoint programmed cell death protein-1 (PD-1) on T cell subsets in PCM patients according to disease course and cytogenetic abnormalities. This study aimed to find a target group suitable for therapeutic use of PD-1 blockade in PCM. Methods: A total of 188 bone marrow (BM) samples from 166 PCM patients and 32 controls were prospectively collected between May 2016 and May 2017. PD-1 expression on BM T cell subsets was measured using flow cytometry. Results: At diagnosis, the median PD-1 expression on CD4+ T cells was 24.6%, which did not significantly differ from that in controls. After stem cell transplantation, PD-1 expression on CD4+ T cells was higher than that at diagnosis (P<0.001), regardless of residual disease. PD-1 expression on CD4+ T cells in patients with residual disease after chemotherapy was significantly higher than that at diagnosis (P=0.001) and after complete remission following chemotherapy (P=0.044). PD-1 expression on CD8+ T cells was higher in PCM patients with cytogenetic abnormalities, including monosomy 13, 1q gain, complex karyotype, and hypodiploidy. Conclusions: PD-1 blockade might have therapeutic potential in refractory PCM patients after chemotherapy, especially in those with high- or intermediate-risk cytogenetic abnormalities.
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