Targeting the TumorMicroenvironment for Enhancing Chemotherapy in HematologicMalignancies

Crespo, Luis; Zhang, Xinwei; Tao, Jianguo

doi:10.1007/978-90-481-9704-0_11

Cited by 2 publications

(4 citation statements)

References 115 publications

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“…Increased levels of bFGF have been observed in CLL patients and correlate with the resistance to fludarabine [48]. Further deregulation of the FGF pathway has been reported in patients with multiple myeloma [43]. Anti-apoptotic effects of VEGF on ALL and CLL cells have been documented and involve alteration of BCL-2 family members and signalling through MAPK pathways.…”

Section: Accepted Manuscriptmentioning

confidence: 98%

“…TGF-β has been documented to display an inhibitory effect on haematopoiesis. However, leukemia cells are often resistant to this inhibition despite increased production of TGF-β by bone marrow stromal cells from leukemia patients [43][44][45][46]. Although TGF-β has been named the molecular Jekyll and Hyde of cancer, recent evidence indicate that TGF-β neutralising antibody in combination with cytarabine (that interferes with DNA synthesis) and CXCR4 antagonist plerixafor increased survival in leukemia mouse model [47].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…Other growth factors including basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) have also been reported as important in affecting leukemia development and bone marrow-mediated resistance to chemotherapy [43]. Increased levels of bFGF have been observed in CLL patients and correlate with the resistance to fludarabine [48].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

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The role of microenvironment and immunity in drug response in leukemia

Bakker

Qattan

Mutti

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Leukemia is a cancer of the white blood cells, with over 54,000 new cases per year diagnosed worldwide and a 5-year survival rate below 60%. This highlights a need for research into the mechanisms behind its etiology and causes of therapy failure. The bone marrow microenvironment, in which adult stem cells are maintained in healthy individuals, has been implicated as a source of chemoresistance and disease relapse. Here the various ways that the microenvironment can contribute to the resistance and persistence of leukemia are discussed. The targeting of the microenvironment by leukemia cells to create an environment more suitable for cancer progression is described. The role of soluble factors, drug transporters, microvesicles, as well as the importance of direct cell-cell contact, in addition to the effects of inflammation and immune surveillance in microenvironment-mediated drug resistance are discussed. An overview of the clinical potential of translating research findings to patients is also provided. Understanding of and further research into the role of the bone marrow microenvironment in leukemia progression and relapse are crucial towards developing more effective treatments and reduction in patient morbidity. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza.

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Section: Accepted Manuscriptmentioning

confidence: 98%

Section: Accepted Manuscriptmentioning

confidence: 99%

Section: Accepted Manuscriptmentioning

confidence: 99%

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The role of microenvironment and immunity in drug response in leukemia

Bakker

Qattan

Mutti

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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“…However, leukemia cells are resistant to TGF-b inhibition despite increased production of TGF-b by BM stromal cells (80). Basic fibroblast growth factor (bFGF) and VEGF are said to promote leukemia development and BMmediated resistance to chemotherapy (81).…”

Section: Immunosuppressive Factors In the Tumor Microenvironment Bone Marrow Microenvironment In Leukemiamentioning

confidence: 99%

Optimizing NK Cell-Based Immunotherapy in Myeloid Leukemia: Abrogating an Immunosuppressive Microenvironment

Kaweme

Zhou

2021

Front. Immunol.

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Natural killer (NK) cells are prominent cytotoxic and cytokine-producing components of the innate immune system representing crucial effector cells in cancer immunotherapy. Presently, various NK cell-based immunotherapies have contributed to the substantial improvement in the reconstitution of NK cells against advanced-staged and high-risk AML. Various NK cell sources, including haploidentical NK cells, adaptive NK cells, umbilical cord blood NK cells, stem cell-derived NK cells, chimeric antigen receptor NK cells, cytokine-induced memory-like NK cells, and NK cell lines have been identified. Devising innovative approaches to improve the generation of therapeutic NK cells from the aforementioned sources is likely to enhance NK cell expansion and activation, stimulate ex vivo and in vivo persistence of NK cells and improve conventional treatment response of myeloid leukemia. The tumor-promoting properties of the tumor microenvironment and downmodulation of NK cellular metabolic activity in solid tumors and hematological malignancies constitute a significant impediment in enhancing the anti-tumor effects of NK cells. In this review, we discuss the current NK cell sources, highlight ongoing interventions in enhancing NK cell function, and outline novel strategies to circumvent immunosuppressive factors in the tumor microenvironment to improve the efficacy of NK cell-based immunotherapy and expand their future success in treating myeloid leukemia.

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Targeting the TumorMicroenvironment for Enhancing Chemotherapy in HematologicMalignancies

Cited by 2 publications

References 115 publications

The role of microenvironment and immunity in drug response in leukemia

The role of microenvironment and immunity in drug response in leukemia

Optimizing NK Cell-Based Immunotherapy in Myeloid Leukemia: Abrogating an Immunosuppressive Microenvironment

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