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. 2021 Aug 12:2021:4468140.
doi: 10.1155/2021/4468140. eCollection 2021.

LAG3 and PD1 Regulate CD8+ T Cell in Diffuse Large B-cell Lymphoma Patients

Ying Liu  1   2 , Xinhong Guo  1   2 , Lingbo Zhan  3 , Lei Wang  1   2 , Xinyou Wang  1   2 , Ming Jiang  1   2
Affiliations

LAG3 and PD1 Regulate CD8+ T Cell in Diffuse Large B-cell Lymphoma Patients

Ying Liu et al. Comput Math Methods Med. .

Retraction in

Abstract

Background: Diffuse large B-cell lymphoma (DLBCL) is a clinically and genetically heterogeneous lymphoid malignancy. The unsatisfactory outcome for refractory patients has prompted efforts to explore new therapeutic approaches for DLBCL. However, the mechanisms involved in treatment associated with immune checkpoints remain unclear. This study is aimed at investigating the potential roles of programmed cell death protein 1 (PD1) and lymphocyte activation gene 3 (LAG3) in CD8+ T cells for treatment in DLBCL.

Methods: Utilizing flow cytometry, we examined the content of T cells, the levels of cytokines, and the expression of PD1 and LAG3 in patients with DLBCL as well as in healthy controls. Levels of cytokines in CD8+ T cells from DLBCL patients before and after treatment were compared by blocking of PD1 and LAG3 in magnetic bead-sorted CD8+ T cells.

Results: We found that the proportion of CD4+ T cells and CD8+ T cells was increased in DLBCL patients after treatment. The levels of cytokines trended toward those of healthy controls in treatment. PD1 (+), LAG3 (+), or PD1 (+) LAG3 (+) were all expressed in lower amounts in CD4+ T cells and CD8+ T cells after treatment than in untreated DLBCL patients. In addition, blockade of PD1 and LAG3 in sorted CD8+ T cells markedly inhibited cytokine production in response to treatment.

Conclusion: PD1 and LAG3 in CD8+ T cells may be important targets of therapy and play therapeutic role in patients with DLBCL.

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Conflict of interest statement

All authors declare no competing interests.

Figures

Figure 1
Figure 1
The proportion of T cells in peripheral blood was detected by flow cytometry. (a). The contents of CD4+ and CD8+ T cells in peripheral blood were detected in different groupings by flow cytometry. (b). The contents of Th1, Th2, Th17, and Treg cells in peripheral blood were detected in different groupings by flow cytometry. ∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001. DLBCL: diffuse large B-cell lymphoma; Three: three courses of treatment; Six: six courses of treatment.
Figure 2
Figure 2
The content of cytokines in peripheral blood was detected by CBA kit. ∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001. DLBCL: diffuse large B-cell lymphoma; Three: three courses of treatment; Six: six courses of treatment.
Figure 3
Figure 3
Flow cytometric detection of immune checkpoint expression in CD4+ and CD8+ T cells. (a) The expression of PD1 and LAG3 in CD4+ T cells. ∗P < 0.05 and ∗∗∗P < 0.001. (b) The expression of PD1 and LAG3 in CD8+ T cells. ∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001. DLBCL: diffuse large B-cell lymphoma; Three: three courses of treatment; Six: six courses of treatment.
Figure 4
Figure 4
Immune targets of CD8+ T cell responses to treatment for DLBCL patients. (a) Purity of sorted CD8+ T cells from DLBCL patients. (b) Cytokine production levels in the cells of each group. ∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001 compared with treatment group. DLBCL: diffuse large B-cell lymphoma; PD1: programmed cell death protein 1; LAG3: lymphocyte activation gene 3.
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