Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Dec 31;24(1):2278229.
doi: 10.1080/15384047.2023.2278229. Epub 2023 Nov 14.

Higher PD-1/Tim-3 expression on IFN-γ+ T cells is associated with poor prognosis in patients with acute myeloid leukemia

Shuxin Huang  1 , Yujie Zhao  1 , Wenpu Lai  1 , Jiaxiong Tan  1 , Xue Zheng  2 , Xianfeng Zha  3 , Yangqiu Li  1 , Shaohua Chen  1
Affiliations

Higher PD-1/Tim-3 expression on IFN-γ+ T cells is associated with poor prognosis in patients with acute myeloid leukemia

Shuxin Huang et al. Cancer Biol Ther. .

Abstract

With the success of immune checkpoint inhibitors (ICI), such as anti- programmed death-1 (PD-1) antibody for solid tumors and lymphoma immunotherapy, a number of clinical trials with ICIs have been attempted for acute myeloid leukemia (AML) immunotherapy; however, limited clinical efficacy has been reported. This may be due to the heterogeneity of immune microenvironments and various degrees of T cell exhaustion in patients and may be involved in the IFN-γ pathway. In this study, we first characterized the percentage of PD-1+ and T cell immunoglobulin mucin-domain-containing-3 (Tim-3) +IFN-γ+ T cells in peripheral blood (PB) in AML compared with healthy individuals (HIs) by flow cytometry and further discussed the possibility of the reversal of T cell exhaustion to restore the secretion capacity of cytokines in T cells in AML based on blockade of PD-1 or Tim-3 (anti-PD-1 and anti-Tim-3 antibody) in vitro using a cytokine protein chip. A significantly increased percentage of PD-1+, Tim-3+, and PD-1+Tim-3+ IFN-γ+ T cells was observed in PB from patients with AML in comparison with HIs. Moreover, higher PD-1+IFN-γ+CD3+/CD8+ T cell levels were associated with poor overall survival in AML patients. Regarding leukemia cells, the percentage of Tim-3 in CD117+CD34+ AML cells was positively correlated with PD-1 in IFN-γ+CD4+ T cells. Furthermore, blocking PD-1 and Tim-3 may involve multiple cytokines and helper T cell subsets, mainly Th1 and Treg cells. Blockade of PD-1 or Tim-3 tends to restore cytokine secretion to a certain extent, a synergistic effect shown by the co-blockade of PD-1 and Tim-3. However, we also demonstrated the heterogeneity of secretory cytokines in ICI-treated T cells in AML patients.

Keywords: AML; IFN-γ; PD-1; T cell exhaustion; Tim-3; immune checkpoint inhibitors.

PubMed Disclaimer

Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Increasing PD-1 and Tim-3 on IFN-γ+ T cell subsets in PB in AML.
Figure 2.
Figure 2.
Higher PD-1 and Tim-3 on IFN-γ+ T cell subsets are related with poor prognosis in AML.
Figure 3.
Figure 3.
Distribution and frequency of PD-L1/PD-L2/Gal-9/Tim-3 in AML cells in PB and BM.
Figure 4.
Figure 4.
The characteristics of the secretory cytokines in ICI-treated T cells in vitro detected by protein chip.
See this image and copyright information in PMC

References

    1. Daver N, Alotaibi AS, Bücklein V, Subklewe M.. T-cell-based immunotherapy of acute myeloid leukemia: current concepts and future developments. Leukemia. 2021. May 07;35(7):1843–9. doi: 10.1038/s41375-021-01253-x. - DOI - PMC - PubMed
    1. Wang M, Bu J, Zhou M, Sido J, Lin Y, Liu G, Lin Q, Xu X, Leavenworth JW, Shen E. CD8(+)T cells expressing both PD-1 and TIGIT but not CD226 are dysfunctional in acute myeloid leukemia (AML) patients. Clin Immunol. 2018;190:64–73. 2017 September 13. doi: 10.1016/j.clim.2017.08.021. - DOI - PubMed
    1. Li Z, Philip M, Ferrell PB. Alterations of T-cell-mediated immunity in acute myeloid leukemia. Oncogene. 2020. March 05;39(18):3611–3619. doi: 10.1038/s41388-020-1239-y. - DOI - PMC - PubMed
    1. Huang S, Liang C, Zhao Y, Deng T, Tan J, Zha X, Li Y, Chen S. Increased TOX expression concurrent with PD-1, Tim-3, and CD244 expression in T cells from patients with acute myeloid leukemia. Cytometry B Clin Cytom. 2022;102(2):143–152. 2021 December 17. doi: 10.1002/cyto.b.22049. - DOI - PubMed
    1. Chen X, Du Y, Lin X, Qian Y, Zhou T, Huang Z, CD4+CD25+ regulatory T cells in tumor immunity. Int Immunopharmacol. 2016. March 20;34:244–249. doi: 10.1016/j.intimp.2016.03.009. - DOI - PubMed

Publication types