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Lunch & Poster Display session

12P - The expression of PD-1 alone by T cells is associated with cell activation while the co-expression of TIM-3 indicates exhausted subsets both in peripheral blood and bone marrow of multiple myeloma patients

Date

12 Dec 2019

Session

Lunch & Poster Display session

Presenters

Egor Batorov

Citation

Annals of Oncology (2019) 30 (suppl_11): xi1-xi11. 10.1093/annonc/mdz447

Authors

E. Batorov1, V. Sergeevicheva2, T. Aristova2, S. Sizikova2, G. Ushakova2, A. Maximova1, A. Morenkova1, E. Shevela1, A. Ostanin1, E. Chernykh1

Author affiliations

  • 1 Laboratory Of Cellular Immunology, Research Institute of Fundamental and Clinical Immunology, 630099 - Novosibirsk/RU
  • 2 Department Of Hematology And Bone Marrow Transplantation, Research Institute of Fundamental and Clinical Immunology, 630099 - Novosibirsk/RU
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Abstract 12P

Background

Multiple myeloma (MM) is a lymphoid neoplasm characterized by the accumulation of malignant clones of plasma cells, usually within the bone marrow (BM). Despite the increase of T cells expressing inhibitory signal molecules (ISMs) — PD-1, TIM-3 etc. — having been described in MM, the first results of anti-PD-1 therapy for MM remain modest. ISMs are expressed on T cells and modulate the functional activity. A stable expression of ISMs on T cells is associated with T cell exhaustion, the condition of severe decrease of both cytotoxicity and cytokine secretion. At the same time, ISMs are also expressed by activated T cells. We studied the expression of PD-1 and TIM-3 by circulating and bone marrow (BM) T cells as a manifestation of T cell exhaustion treated MM patients.

Methods

Peripheral blood (PB) and BM samples of 45 MM patients were obtained during routine diagnostic procedures. The expression of PD-1 and TIM-3 by CD4+ and CD8+ T cells, intracellular production of IFNγ and intracellular expression of Ki-67 by T cells and Granzyme B production by CD8+ T cells were assessed using flow cytometry.

Results

Relative counts of PD-1+ subset of CD8+ T cells and both PD-1+ and TIM-3+ subsets of CD4+ T cells were higher in BM compared with PB. BM samples also contained higher amounts of double-positive PD-1+TIM-3+ subsets of CD8+ and CD4+ T cells compared with PB. Percentage of PB CD8+PD-1+, CD4+PD-1+, CD4+TIM-3+, CD8+PD-1+TIM-3+ and CD4+PD-1+TIM-3+ T cells correlated with the content of respective subsets in BM. Both PB and BM CD8+PD-1+ and CD4+PD-1+ T cells of MM patients retain a cytotoxic, proliferative and cytokine-producing potential appropriate to PD-1-negative subsets. On the contrary, the functional activity of CD8+PD-1+TIM-3+ and CD4+PD-1+TIM-3+ T cells was significantly reduced compared with PD-1- and TIM-3-negative subsets.

Conclusion

PD-1+ T cells in MM patients are related to activated rather than exhausted populations. T cell exhaustion is associated with cells co-expressing PD-1 and TIM-3. It is recommended to evaluate T cell subsets co-expressing PD-1, TIM-3 and other ISMs, and to study their functional properties.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

The Russian Science Foundation (grant no. 18-75-00050).

Disclosure

All authors have declared no conflicts of interest.

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