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.
Highlights
Diffuse large B-cell lymphoma (DLBCL) is a clinically and genetically heterogeneous lymphoid malignancy
PD1 (+) lymphocyte activation gene 3 (LAG3) (+) all showed a decreasing trend after treatment compared with untreated DLBCL patients (Figure 3(b)). These results suggested that treatment of DLBCL patients may involve the PD1 and LAG3 immune checkpoints on immune cells
In this study, we found that the distribution of Th1/T helper 2 (Th2) cells changed after treatment in DLBCL patients, and these changes may be associated with the response of patients to therapy
Summary
Diffuse large B-cell lymphoma (DLBCL) is a clinically and genetically heterogeneous lymphoid malignancy. 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+. The use of rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (R-CHOP) standard therapy has significantly improved overall survival in DLBCL [6]. R-DA-EPOCH (rituximab, doxorubicin, etoposide, prednisone, vincristine, cyclophosphamide) was commonly used for relapsed DLBCL patients [2]. Existing methods maynot accurately or effectively predict therapeutic efficacy before treatment of DLBCL [9]. Understanding the potential effect mechanism of the chemotherapeutic agent acting on DLBCL is essential to improve protocols for improving patient prognosis
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