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

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Ying Liu ◽  
Xinhong Guo ◽  
Lingbo Zhan ◽  
Lei Wang ◽  
Xinyou Wang ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Immune Checkpoints ◽  
Healthy Controls ◽  
Large B Cell Lymphoma ◽  
Large B Cell

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.

scholarly journals Corrigendum to “Genetic Mutations of Tim-3 Ligand and Exhausted Tim-3+ CD8+ T Cells and Survival in Diffuse Large B Cell Lymphoma”

2021 ◽  
Vol 2021 ◽  
pp. 1-1
Author(s):  
Tingting Zhang ◽  
Tianyuan Ren ◽  
Zheng Song ◽  
Jing Zhao ◽  
Lei Jiao ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Cd8 T Cells ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Genetic Mutations ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals Predominance of CD4+ T Cells in T-Cell/Histiocyte-Rich Large B-Cell Lymphoma and Identification of a Subset of Patients With Peripheral B-Cell Lymphopenia

2017 ◽  
Vol 147 (6) ◽  
pp. 596-603 ◽  
Author(s):  
Christian Kunder ◽  
Michael J. Cascio ◽  
Anthony Bakke ◽  
Girish Venkataraman ◽  
Dennis P. O’Malley ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Cd4 T Cells ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals Effect of interleukin 21 and its receptor on CD8+ T cells in the pathogenesis of diffuse large B-cell lymphoma

2014 ◽  
Vol 8 (1) ◽  
pp. 421-425 ◽  
Author(s):  
ZHANSHAN CHA ◽  
HAIHUI GU ◽  
HUIJUN GUO ◽  
XIAOHUA TU ◽  
YAN ZANG ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Cd8 T Cells ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Interleukin 21 ◽  
Large B Cell

scholarly journals Genetic Mutations of Tim-3 Ligand and Exhausted Tim-3+ CD8+ T Cells and Survival in Diffuse Large B Cell Lymphoma

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Tingting Zhang ◽  
Tianyuan Ren ◽  
Zheng Song ◽  
Jing Zhao ◽  
Lei Jiao ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Median Survival ◽  
Cd8 T Cells ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Genetic Mutations ◽  
Mrna Levels ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Tim-3 is a promising target for antitumor immunotherapy. A number of clinical trials are evaluating the efficacy of anti-Tim-3 therapies as a single agent or combinations in solid tumors and haematologic malignancies. However, there remains a considerable lack of data on Tim-3 signalling, especially the genetic characteristics and immune microenvironment, in diffuse large B cell lymphoma (DLBCL). Herein, we identified three genetic mutations in galectin-9, a major ligand of Tim-3, in six patients with DLBCL (6/188, 3.2%) that were not detected in the COSMIC database. The Oncomine database showed that the mRNA levels of Tim-3 were higher in DLBCL cells than those in normal B cells. Multiplexed immunofluorescence revealed that patients with Tim-3-expressing tumor-infiltrating lymphocytes (Tim-3+ TILs) exhibited poor outcomes than those with Tim-3- TILs ( p = 0.041 ). The median survival times of these patients were 65.0 (95% confidence interval (CI): 71.2–88.6) and 79.9 months (95% CI: 54.4–75.6), respectively. Furthermore, we defined a novel subtype of exhausted T cells, named as exhausted Tim-3+ CD8+ T cells, and found that patients with exhausted Tim-3+ CD8+ T cells (median survival, 62.8 months, 95% CI: 50.0–75.6) exhibited shorter survival than those with nonexhausted Tim-3- CD8+ T cells (median survival, 82.5 months, 95% CI: 72.0–92.9; p = 0.034 ). Overall, these findings provide the genetic status of the Tim-3 ligand in DLBCL. Patients with Tim-3+ TILs and exhausted Tim-3+ CD8+ T cells exhibited inferior survival, thus highlighting the possibility of potential therapeutic applications of the inhibition of Tim-3 alone or in combination with other immune checkpoints for treatment of patients with DLBCL.

scholarly journals Gene expression profiling-based risk prediction and profiles of immune infiltration in diffuse large B-cell lymphoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Selin Merdan ◽  
Kritika Subramanian ◽  
Turgay Ayer ◽  
Johan Van Weyenbergh ◽  
Andres Chang ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
B Cell ◽  
Risk Prediction ◽  
Expression Profiling ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Gene Signatures ◽  
Large B Cell Lymphoma ◽  
Large B Cell

AbstractThe clinical risk stratification of diffuse large B-cell lymphoma (DLBCL) relies on the International Prognostic Index (IPI) for the identification of high-risk disease. Recent studies suggest that the immune microenvironment plays a role in treatment response prediction and survival in DLBCL. This study developed a risk prediction model and evaluated the model’s biological implications in association with the estimated profiles of immune infiltration. Gene-expression profiling of 718 patients with DLBCL was done, for which RNA sequencing data and clinical covariates were obtained from Reddy et al. (2017). Using unsupervised and supervised machine learning methods to identify survival-associated gene signatures, a multivariable model of survival was constructed. Tumor-infiltrating immune cell compositions were enumerated using CIBERSORT deconvolution analysis. A four gene-signature-based score was developed that separated patients into high- and low-risk groups. The combination of the gene-expression-based score with the IPI improved the discrimination on the validation and complete sets. The gene signatures were successfully validated with the deconvolution output. Correlating the deconvolution findings with the gene signatures and risk score, CD8+ T-cells and naïve CD4+ T-cells were associated with favorable prognosis. By analyzing the gene-expression data with a systematic approach, a risk prediction model that outperforms the existing risk assessment methods was developed and validated.

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