scholarly journals Targeting the tumor microenvironment in B-cell lymphoma: challenges and opportunities

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yingyue Liu ◽  
Xiangxiang Zhou ◽  
Xin Wang
Keyword(s):  
Tumor Microenvironment ◽  
B Cell ◽  
Hematological Malignancies ◽  
Immune Escape ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Clinical Value ◽  
Challenges And Opportunities ◽  
Biological Heterogeneity ◽  
Novel Therapeutic Strategies

AbstractB-cell lymphoma is a group of hematological malignancies with high clinical and biological heterogeneity. The pathogenesis of B-cell lymphoma involves a complex interaction between tumor cells and the tumor microenvironment (TME), which is composed of stromal cells and extracellular matrix. Although the roles of the TME have not been fully elucidated, accumulating evidence implies that TME is closely relevant to the origination, invasion and metastasis of B-cell lymphoma. Explorations of the TME provide distinctive insights for cancer therapy. Here, we epitomize the recent advances of TME in B-cell lymphoma and discuss its function in tumor progression and immune escape. In addition, the potential clinical value of targeting TME in B-cell lymphoma is highlighted, which is expected to pave the way for novel therapeutic strategies.

scholarly journals Proteomic analysis in diffuse large B-cell lymphoma identifies dysregulated tumor microenvironment proteins in non-GCB/ABC subtype patients

2021 ◽  
pp. 1-14
Author(s):  
Susanne Bram Ednersson ◽  
Mimmie Stern ◽  
Henrik Fagman ◽  
Herman Nilsson-Ehle ◽  
Sverker Hasselblom ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
B Cell ◽  
Proteomic Analysis ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Distinct roles for PARP-1 and PARP-2 in c-Myc-driven B-cell lymphoma in mice

Blood ◽  
2021 ◽  
Author(s):  
Miguel A Galindo-Campos ◽  
Nura Lutfi ◽  
Sarah Bonnin ◽  
Carlos Martínez ◽  
Talia Velasco-Hernandez ◽  
...  
Keyword(s):  
Dna Damage ◽  
B Cells ◽  
B Cell ◽  
Immune Escape ◽  
Cell Lymphoma ◽  
Tumour Progression ◽  
Cancer Therapeutics ◽  
B Cell Lymphoma ◽  
B Cell Lymphomas ◽  
Parp 1

Dysregulation of the c-Myc oncogene occurs in a wide variety of haematologic malignancies and its overexpression has been linked with aggressive tumour progression. Here, we show that Poly (ADP-ribose) polymerase (PARP)-1 and PARP-2 exert opposing influences on progression of c-Myc-driven B-cell lymphomas. PARP-1 and PARP-2 catalyse the synthesis and transfer of ADP-ribose units onto amino acid residues of acceptor proteins in response to DNA-strand breaks, playing a central role in the response to DNA damage. Accordingly, PARP inhibitors have emerged as promising new cancer therapeutics. However, the inhibitors currently available for clinical use are not able to discriminate between individual PARP proteins. We found that genetic deletion of PARP-2 prevents c-Myc-driven B-cell lymphomas, while PARP-1-deficiency accelerates lymphomagenesis in the Em-Myc mouse model of aggressive B-cell lymphoma. Loss of PARP-2 aggravates replication stress in pre-leukemic Em-Myc B cells resulting in accumulation of DNA damage and concomitant cell death that restricts the c-Myc-driven expansion of B cells, thereby providing protection against B-cell lymphoma. In contrast, PARP-1-deficiency induces a proinflammatory response, and an increase in regulatory T cells likely contributing to immune escape of B-cell lymphomas, resulting in an acceleration of lymphomagenesis. These findings pinpoint specific functions for PARP-1 and PARP-2 in c-Myc-driven lymphomagenesis with antagonistic consequences that may help inform the design of new PARP-centred therapeutic strategies with selective PARP-2 inhibition potentially representing a new therapeutic approach for the treatment of c-Myc-driven tumours.

scholarly journals B Cell Lymphoma 2: A Potential Therapeutic Target for Cancer Therapy

2021 ◽  
Vol 22 (19) ◽  
pp. 10442
Author(s):  
Manzar Alam ◽  
Sabeeha Ali ◽  
Taj Mohammad ◽  
Gulam Mustafa Hasan ◽  
Dharmendra Kumar Yadav ◽  
...  
Keyword(s):  
B Cell ◽  
Cancer Progression ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cancer Development ◽  
Cancer Cell Growth ◽  
Growth And Survival ◽  
Investigational Agents ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Defects in the apoptosis mechanism stimulate cancer cell growth and survival. B cell lymphoma 2 (Bcl-2) is an anti-apoptotic molecule that plays a central role in apoptosis. Bcl-2 is the founding constituent of the Bcl-2 protein family of apoptosis controllers, the primary apoptosis regulators linked with cancer. Bcl-2 has been identified as being over-expressed in several cancers. Bcl-2 is induced by protein kinases and several signaling molecules which stimulate cancer development. Identifying the important function played by Bcl-2 in cancer progression and development, and treatment made it a target related to therapy for multiple cancers. Among the various strategies that have been proposed to block Bcl-2, BH3-mimetics have appeared as a novel group of compounds thanks to their favorable effects on many cancers within several clinical settings. Because of the fundamental function of Bcl-2 in the regulation of apoptosis, the Bcl-2 protein is a potent target for the development of novel anti-tumor treatments. Bcl-2 inhibitors have been used against several cancers and provide a pre-clinical platform for testing novel therapeutic drugs. Clinical trials of multiple investigational agents targeting Bcl-2 are ongoing. This review discusses the role of Bcl-2 in cancer development; it could be exploited as a potential target for developing novel therapeutic strategies to combat various types of cancers. We further highlight the therapeutic activity of Bcl-2 inhibitors and their implications for the therapeutic management of cancer.

The effect of biological heterogeneity on R-CHOP treatment outcome in diffuse large B-cell lymphoma across five international regions

2016 ◽  
Vol 58 (5) ◽  
pp. 1178-1183
Author(s):  
Robert Carr ◽  
Hilal Ozdag ◽  
Nilgun Tekin ◽  
Timothy Morris ◽  
Paulette Conget ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Biological Heterogeneity ◽  
Large B Cell

scholarly journals Inflammatory Cells in Diffuse Large B Cell Lymphoma

2020 ◽  
Vol 9 (8) ◽  
pp. 2418
Author(s):  
Roberto Tamma ◽  
Girolamo Ranieri ◽  
Giuseppe Ingravallo ◽  
Tiziana Annese ◽  
Angela Oranger ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
B Cell ◽  
Tumor Cells ◽  
Immune Cells ◽  
Tumor Antigens ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Diffuse large B cell lymphoma (DLBCL), known as the most common non-Hodgkin lymphoma (NHL) subtype, is characterized by high clinical and biological heterogeneity. The tumor microenvironment (TME), in which the tumor cells reside, is crucial in the regulation of tumor initiation, progression, and metastasis, but it also has profound effects on therapeutic efficacy. The role of immune cells during DLBCL development is complex and involves reciprocal interactions between tumor cells, adaptive and innate immune cells, their soluble mediators and structural components present in the tumor microenvironment. Different immune cells are recruited into the tumor microenvironment and exert distinct effects on tumor progression and therapeutic outcomes. In this review, we focused on the role of macrophages, Neutrophils, T cells, natural killer cells and dendritic cells in the DLBCL microenvironment and their implication as target for DLBCL treatment. These new therapies, carried out by the induction of adaptive immunity through vaccination or passive of immunologic effectors delivery, enhance the ability of the immune system to react against the tumor antigens inducing the destruction of tumor cells.

scholarly journals Immune cell constitution in the tumor microenvironment predicts the outcome in diffuse large B-cell lymphoma

Haematologica ◽  
2020 ◽  
pp. haematol.2019.243626 ◽  
Author(s):  
Matias Autio ◽  
Suvi-Katri Leivonen ◽  
Oscar Brück ◽  
Satu Mustjoki ◽  
Judit Mészáros Jørgensen ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
B Cell ◽  
Immune Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell
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