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

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.

Prediction significance of autophagy-related genes in survival probability and drug resistance in diffuse large B-cell lymphoma

“…Compared to healthy individuals, DLBCL patients, especially those at high risk, exhibited decreased counts of CD3+, CD4+, and CD8+ T cells, as well as natural killer (NK) cells [ 84 ]. Remarkably, the proportion of CD4+ and CD8+ T cells increased in these patients after treatment [ 85 ]. Moreover, a recent study demonstrated that higher CD8+ T cell levels were associated with improved immunotherapy outcomes in DLBCL [ 86 ].…”

A unique expression pattern of LAG3 distinct from that of other immune checkpoints in diffuse large B‐cell lymphoma

“…The anti‐human LAG‐3 antibody relatlimab was first introduced in 2019 29 . Although there are few clinical trial results for anti‐LAG‐3 antibodies in lymphoma, several studies have experimentally shown the potential of LAG‐3 as a target for DLBCL treatment 30,31 . In chronic lymphocytic leukemia patients, treatment of peripheral blood mononuclear cells with relatlimab depleted leukemia cells and restored NK‐cell and T‐cell‐mediated responses 32 .…”

Comprehensive Analysis of the Prognosis and Correlations with Immune Infiltration of CXC Chemokine Family Members in Diffuse Large B-cell Lymphoma

“…In recent years, the suppression therapy of immune checkpoints has become a breakthrough point for refractory/relapsed malignant tumors. Some scholars have found that the combined inhibition of PD1/PD-L1, PD1/CTLA4, PD1/TIM-3, and PD1/LAG3 can significantly inhibit cytokines in response to malignant neoplasm therapy [5,[41][42][43][44]. T cell immunoglobulin and ITIM domain (TIGIT), as an inhibitory receptor, is an emerging cancer immunotherapy target.…”