Ann Lab Med.  2021 May;41(3):259-267. 10.3343/alm.2021.41.3.259.

Immune Checkpoint Programmed Cell Death Protein-1 (PD-1) Expression on Bone Marrow T Cell Subsets in Patients With Plasma Cell Myeloma

• Lee MY
• Park CJ
• Cho YU
• You E
• Jang S
• Seo EJ
• Lee JH
• Yoon DH
• Suh C

• KMID: 2512683
• DOI: http://doi.org/10.3343/alm.2021.41.3.259

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.

Keyword

Plasma cell myeloma; Immune checkpoint programmed cell death protein-1 (PD-1); Flow cytometry; T cell subset

Figure

• 

  Fig. 1 Percentages of PD-1 expression on (A) CD4+ T cells and (B) CD8+ T cells in the controls and PCM patients with various disease states. In each box plot, the median value is reported beside the box. The upper end, lower end, and inner line of the boxes correspond to the 3rd quartile, 1st quartile, and median value, respectively. Error bars denote minimum and maximum values, and circles indicate outlier values. Statistically significant differences are marked with *if P<0.05, with †if P<0.01, and with ‡if P<0.001. Abbreviations: CTx-CR, complete remission after chemotherapy; CTx-RD, residual disease after chemotherapy; PD-1, immune checkpoint programmed cell death protein-1; PCM, Plasma cell myeloma; SCT-CR, complete remission after stem cell transplantation; SCT-RD, residual disease after stem cell transplantation.

• 

  Fig. 2 Correlation between PD-1 expression on T cell subsets and involved/uninvolved free light chain ratio in PCM. The PD-1 expression on CD8+ T cells was weakly correlated with involved/uninvolved free light chain ratio; however, the PD-1 expression on CD4+ T cells was not correlated with involved/uninvolved free light chain ratio. Abbreviations: PCM, plasma cell myeloma; PD-1, immune checkpoint programmed cell death protein-1.

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