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Updated: Jun 30, 2026
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
PD-1/TIM-3-Expressing Myeloid Cells During the Early Immune Reconstitution in Patients with Multiple Myeloma After
Polina A Serpeninova1, Tamara V Tyrinova1, Egor V Batorov1
1Laboratory of Cellular Immunotherapy, Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia.
Background:
In multiple myeloma (MM), immune checkpoint blockade is being explored as a treatment strategy. However, the role of inhibitory checkpoint receptors on myeloid cells remains poorly understood. The aim of our study was to investigate the expression of PD-1 and TIM-3 on monocytes and monocytic myeloid-derived suppressor cells (M-MDSCs) and their contribution to early immune reconstitution.
Methods:
The count of monocytic cells and expression of PD-1 and TIM-3 was assessed by flow cytometry.
Results:
At the engraftment, monocyte subsets counts were similar to pre-transplant values, while the relative content of M-MDSCs was significantly higher. The frequencies of TIM-3-positive cells among intermediate and non-classical monocytes were significantly increased. Incubation of mononuclear cells of MM patients in remission with homeostatic cytokines led to a significant increase in intermediate monocytes and a trend to an increase in the M-MDSCs count and stimulated the expression of PD-1 and TIM-3. PD-1 and TIM-3 expression on monocytes and M-MDSCs inversely correlated with lymphocyte count at the engraftment. TIM-3 expression on monocytic cells was associated with regulatory T-cell count. After auto-HSCT, PD-1/TIM-3-expressing cells exhibited significantly elevated IL-10 production (with decreased TNFα production).
Conclusion:
PD-1 and TIM-3 on monocytic cells may play a significant role in immune reconstitution.
Insights
Immune checkpoint receptors programmed death-1 (PD-1) and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) on myeloid cells are crucial for immune reconstitution after multiple myeloma treatment.
Area of Science:
- Immunology
- Oncology
- Hematology
Background:
- Immune checkpoint blockade is a promising strategy for multiple myeloma (MM).
- The role of inhibitory checkpoint receptors on myeloid cells in MM is not well understood.
- Investigating programmed death-1 (PD-1) and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) on myeloid cells is critical for understanding immune reconstitution.
Purpose of the Study:
- To investigate the expression of PD-1 and TIM-3 on monocytes and monocytic myeloid-derived suppressor cells (M-MDSCs).
- To determine the contribution of these cells to early immune reconstitution in multiple myeloma patients.
Main Methods:
- Flow cytometry was used to assess monocytic cell counts and PD-1/TIM-3 expression.
- Analysis was performed on patients undergoing autologous hematopoietic stem cell transplantation (auto-HSCT) for multiple myeloma.
Main Results:
- M-MDSCs increased significantly post-transplant, with elevated TIM-3 expression on monocyte subsets.
- PD-1 and TIM-3 expression on monocytic cells inversely correlated with lymphocyte counts.
- PD-1/TIM-3-expressing cells showed increased IL-10 and decreased TNFα production post-auto-HSCT.
Conclusions:
- PD-1 and TIM-3 on monocytic cells play a significant role in immune reconstitution following multiple myeloma treatment.
- Targeting these checkpoints on myeloid cells may be a therapeutic strategy to improve immune recovery.
