Immunological microenvironment gene expression in patients with diffuse large B cell non Hodgkin lymphoma

Elhelbawy, Nesreen G; Nassar, Adel; El-Torgoman, Abd El-Monem Abd El-Kader; Saber, Safa M; Badr, Eman

doi:10.1016/j.bbrep.2020.100731

Cited by 8 publications

(6 citation statements)

References 37 publications

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“…Programmed cell death 1 (PD‐1) immune checkpoint proteins on the surface of T cells function as “off switches” upon coming into contact with the proteins of other (cancerous) cells, thereby preventing the immune system from attacking 10 . A recent study showed that overexpression of PD‐1 proteins is associated with high tumor aggressiveness in DLBCL 11,12 . Therefore, PD‐1 inhibitor drugs may be immunological targets for R/R DLBCL therapy.…”

Section: Introductionmentioning

confidence: 99%

“…10 A recent study showed that overexpression of PD-1 proteins is associated with high tumor aggressiveness in DLBCL. 11,12 Therefore, PD-1 inhibitor drugs may be immunological targets for R/R DLBCL therapy. The CAR T cells, T cells with high PD-1 expression that have been genetically altered in a lab, have a reduced anti-tumor activity, which results in the failure of this therapy.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy of programmed cell death 1 inhibitor maintenance therapy after combined treatment with programmed cell death 1 inhibitors and anti‐CD19‐chimeric antigen receptor T cells in patients with relapsed/refractory diffuse large B‐cell lymphoma and high tumor burden

Deng

et al. 2022

Hematological Oncology

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We studied the efficacy and safety of the combined treatment with programmed cell death 1 (PD‐1) inhibitors and anti‐CD19 chimeric antigen receptor (CAR) T‐cell therapy and subsequent PD‐1 inhibitor maintenance treatment in patients with relapsed/refractory (R/R) diffuse large B‐cell lymphoma (DLBCL) and high tumor burden. Forty‐four R/R DLBCL patients with high tumor burden were enrolled in this study. The experimental group of 26 patients received combined therapy with PD‐1 inhibitors and anti‐CD19‐CAR T cells, while the control group of 18 patients received anti‐CD19‐CAR T‐cell therapy alone. The objective response rate (ORR) was 65.39% and 61.11% in the combination and control groups, respectively. The PD‐1 inhibitor maintenance therapy was selected for patients who achieved complete response or partial response in the combination therapy group. Progression‐free survival and overall survival rates in the combination group were higher than those in the control group 3 and 12 months after CAR T‐cell infusion. There was no significant difference in the grade of cytokine release syndrome or immune effector cell associated neurotoxic syndrome between the two groups. In the maintenance therapy group, only eight patients experienced grade 1 Common Terminology Criteria for Adverse Events (CTCAE) and three grade 2 CTCAE. Overall, we found that the ORR was not affected by the combination therapy with PD‐1 inhibitors and anti‐CD19‐CAR T cells. However, patients who had achieved the ORR might benefit from PD‐1 inhibitor maintenance therapy after combination therapy without increased side effects.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Efficacy of programmed cell death 1 inhibitor maintenance therapy after combined treatment with programmed cell death 1 inhibitors and anti‐CD19‐chimeric antigen receptor T cells in patients with relapsed/refractory diffuse large B‐cell lymphoma and high tumor burden

Deng

et al. 2022

Hematological Oncology

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“…When motivated, it produced regulation of certain molecules, on whose surface shared in T-lymphocyte stimulation. 29 , 30 …”

Section: Discussionmentioning

confidence: 99%

Identification and Development of a 4-Gene Ferroptosis Signature Predicting Overall Survival for Diffuse Large B-Cell Lymphoma

Zhang

et al. 2023

Technol Cancer Res Treat

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Background: Diffuse large B-cell lymphoma (DLBCL) is a well-differentiated disease, which makes the diagnosis and therapeutic strategy a difficult problem. While ferroptosis, as an iron-dependent form of regulated cell death, it plays an important role in causing several types of cancer. This study is aimed at exploring the prognostic value of ferroptosis-related genes in DLBCL. Methods: In our study, mRNA expression and matching clinical data of DLBCL patients were derived from Gene Expression Omnibus (GEO) database. First, multivariate cox regression model and nomogram which can predict the DLBCL patients’ prognosis were built and validated. The multigene signature was constructed and optimized by the least absolute shrinkage and selection operator (LASSO) cox regression model. Also, ferroptosis-related subtypes were developed by consistent cluster. Last but not least, we explored the association between categories of infiltrating immune cells and model genes’ expression. Results: Our results showed that 27 gene expressions were correlated with overall survival (OS) in the univariate cox regression analysis. A 4-gene signature was constructed through these genes to stratify patients into high-low risk groups using risk score derived from model (model 1:gene expression model). The OS of patients in the high-risk group was shorter than that of patients in the low-risk group in the TNM stage and clinically distinct subtypes (activated B cell [ABC], germinal center B cell [GCB]) ( P < .001). Furthermore, it was shown that the risk score was an independent factor in clinical cox regression model for OS (model 2:clinical model) (HR>1, P < .010). Besides, in consistent cluster analysis, ferroptosis prognosis status was different among 3 subtypes. Moreover, the correlation analysis between 4-gene with immune cells showed dendritic cells may be significantly associated with DLBCL. Conclusion: This research constructed an innovative ferroptosis-related gene signature for prognostic estimation of DLBCL patients. Solutions targeting ferroptosis could be an important therapeutic intervention for DLBCL.

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“…Several lines of evidence suggest an important prognostic significance of CD11c(+) dendritic cells for lymphoma. First, higher levels of CD11c in serum correlate with lower Lugano stages and better overall survival [ 38 ]. Second, small cohorts have demonstrated the survival benefit of high CD11c expression in tumor tissue [ 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

DecreasedCD11c‐positive dendritic cells in the tumor microenvironment predict double‐hit/triple‐hit genotype and survival in diffuse large B‐cell lymphoma

Yuan

Chuang

Pei-yuan

et al. 2022

The Journal of Pathology CR

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Diffuse large B‐cell lymphoma (DLBCL) is the most common type of non‐Hodgkin lymphoma and is a potentially curable disease. However, it is heterogenous, and the prognosis is poor if the tumor cells harbor fusions involving MYC and BCL2 or MYC and BCL6 (double‐hit [DH] lymphoma), or fusions involving all three genes (triple‐hit [TH] lymphoma). Fluorescence in situ hybridization is currently the gold standard for confirming the presence of DH/TH genotypes. However, the test is laborious and not readily available in some laboratories. Germinal center B (GCB) signatures and dual expression of MYC and BCL2 are commonly used as initial screening markers (traditional model) in clinical practice. Our study proposes immunohistochemical markers for more conveniently and accessibly screening DH/TH genotypes in DLBCL. We retrospectively reviewed the clinical and pathological parameters of patients with DLBCL. We assessed the proliferative index, apoptotic index, and tumor microenvironment (TME), with regard to T cells and CD11c(+) dendritic cells, in formalin‐fixed paraffin‐embedded tissue. We then generated a decision tree as a screening algorithm to predict DH/TH genotypes and employed decision curve analysis to demonstrate the superiority of this new model in prediction. We also assessed the prognostic significance of related parameters. Our study revealed that GCB subtypes, a Ki67 proliferative index higher than 70%, and BCL2 expression were significantly associated with DH/TH genotypes. Decreased CD11c(+) dendritic cells in the TME indicated additional risk. Our proposed screening algorithm outperformed a traditional model in screening for the DH/TH genotypes. In addition, decreased CD11c(+) dendritic cells in the DLBCL TME were an independent unfavorable prognosticator. In conclusion, we provide a convenient, well‐performing model that predicts DH/TH genotypes in DLBCL. The prognostic significance of CD11c(+) dendritic cells in the TME might influence the classification and development of immunotherapy for DLBCL in the future.

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Immunological microenvironment gene expression in patients with diffuse large B cell non Hodgkin lymphoma

Cited by 8 publications

References 37 publications

Efficacy of programmed cell death 1 inhibitor maintenance therapy after combined treatment with programmed cell death 1 inhibitors and anti‐CD19‐chimeric antigen receptor T cells in patients with relapsed/refractory diffuse large B‐cell lymphoma and high tumor burden

Efficacy of programmed cell death 1 inhibitor maintenance therapy after combined treatment with programmed cell death 1 inhibitors and anti‐CD19‐chimeric antigen receptor T cells in patients with relapsed/refractory diffuse large B‐cell lymphoma and high tumor burden

Identification and Development of a 4-Gene Ferroptosis Signature Predicting Overall Survival for Diffuse Large B-Cell Lymphoma

DecreasedCD11c‐positive dendritic cells in the tumor microenvironment predict double‐hit/triple‐hit genotype and survival in diffuse large B‐cell lymphoma

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