Intercellular Mitochondrial Transfer in the Tumor Microenvironment

Sahinbegovic, Hana; Jelı́nek, Tomáš; Hrdinka, Matouš; Bagó, Juli R.; Turi, Marcello; Ševčíková, Tereza; Kurtovic-Kozaric, Amina; Šimíček, Michal

doi:10.3390/cancers12071787

Cited by 32 publications

(28 citation statements)

References 85 publications

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“…Isatuximab is also capable of modulating the enzymatic function of CD38 [ 19 ]. Based on preclinical data, blocking CD38 prevents mitochondrial trafficking from stromal cells to MM cells thereby possibly depleting energy sources for MM cell growth [ 9 , 20 ]. Since CD38 is expressed on other immune cells, other mechanisms of action include immunomodulatory effects especially seen on T and NK cells [ 4 ].…”

Section: Anti-cd38 Monoclonal Antibodiesmentioning

confidence: 99%

Monoclonal Antibodies and Antibody Drug Conjugates in Multiple Myeloma

Radocha

Donk

Weisel

2021

Cancers

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Multiple myeloma is the second most common hematologic malignancy. Current treatment strategies are mainly based on immunomodulatory drugs, proteasome inhibitors or combination of both. Novel agents added to these backbone treatments represent a promising strategy in treatment of newly diagnosed as well as relapsed and refractory multiple myeloma patients. In this respect, the incorporation of monoclonal antibodies into standard-of-care regimens markedly improved prognosis of myeloma patients during the last years. More specifically, monoclonal anti-CD38 antibodies, daratumumab and isatuximab, have been implemented into treatment strategies from first-line treatment to refractory disease. In addition, the monoclonal anti-SLAM-F7 antibody elotuzumab in combination with immunomodulatory drugs has improved the clinical outcomes of patients with relapsed/refractory disease. Belantamab mafodotin is the first approved antibody drug conjugate directed against B cell maturation antigen and is currently used as a monotherapy for patients with advanced disease. This review focuses on clinical efficacy and safety of monoclonal antibodies as well as antibody drug conjugates in multiple myeloma.

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Section: Anti-cd38 Monoclonal Antibodiesmentioning

confidence: 99%

Monoclonal Antibodies and Antibody Drug Conjugates in Multiple Myeloma

Radocha

Donk

Weisel

2021

Cancers

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“…Aggressive cancers become resistant to most chemotherapeutic drugs owing to the presence of clusters of drug-resistant cancer stem cells that exhibit an altered metabolic profile (117). A number of studies highlighted the importance of mitochondria-dependent metabolic reprogramming in the appearance of tumor evasion mechanisms and develop drug resistance (118). A novel mechanism of intercellular communication based on a horizontal transfer of mitochondria between non-tumor and malignant cells was described, which showed the phenomenon of direct mitochondria sharing could also contribute to resistance to existing drug combinations and possibly further promote tumor growth (118)(119)(120).…”

Section: Pgc-1a/ppar-g Signaling In Hypoxia-induced Chemoresistance In Nsclcmentioning

confidence: 99%

SIRT1/PGC-1α/PPAR-γ Correlate With Hypoxia-Induced Chemoresistance in Non-Small Cell Lung Cancer

Luo

et al. 2021

Front. Oncol.

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Resistance is the major cause of treatment failure and disease progression in non-small cell lung cancer (NSCLC). There is evidence that hypoxia is a key microenvironmental stress associated with resistance to cisplatin, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), and immunotherapy in solid NSCLCs. Numerous studies have contributed to delineating the mechanisms underlying drug resistance in NSCLC; nevertheless, the mechanisms involved in the resistance associated with hypoxia-induced molecular metabolic adaptations in the microenvironment of NSCLC remain unclear. Studies have highlighted the importance of posttranslational regulation of molecular mediators in the control of mitochondrial function in response to hypoxia-induced metabolic adaptations. Hypoxia can upregulate the expression of sirtuin 1 (SIRT1) in a hypoxia-inducible factor (HIF)-dependent manner. SIRT1 is a stress-dependent metabolic sensor that can deacetylate some key transcriptional factors in both metabolism dependent and independent metabolic pathways such as HIF-1α, peroxisome proliferator-activated receptor gamma (PPAR-γ), and PPAR-gamma coactivator 1-alpha (PGC-1α) to affect mitochondrial function and biogenesis, which has a role in hypoxia-induced chemoresistance in NSCLC. Moreover, SIRT1 and HIF-1α can regulate both innate and adaptive immune responses through metabolism-dependent and -independent ways. The objective of this review is to delineate a possible SIRT1/PGC-1α/PPAR-γ signaling-related molecular metabolic mechanism underlying hypoxia-induced chemotherapy resistance in the NSCLC microenvironment. Targeting hypoxia-related metabolic adaptation may be an attractive therapeutic strategy for overcoming chemoresistance in NSCLC.

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“…Finally, intercellular mitochondrial transfer through tunneling nanotubes and extracellular vesicles is regarded as a new and exciting crosstalk mechanism between BMM cells and leukaemic cells. Functional exchange of mitochondria between donor BM-MSCs and recipient leukaemic cells contribute to enhanced leukaemic cell metabolism, increased proliferative capacity, drug resistance, and disease relapse [160,161]. Therefore, targeting molecular components involved in mitochondrial transfer, such as CD38, could present a novel avenue for elimination of minimal residual disease in treatment for leukaemia [161].…”

Section: Emerging Therapies: Immunotherapies and Mitochondrial-targetmentioning

confidence: 99%

“…Functional exchange of mitochondria between donor BM-MSCs and recipient leukaemic cells contribute to enhanced leukaemic cell metabolism, increased proliferative capacity, drug resistance, and disease relapse [160,161]. Therefore, targeting molecular components involved in mitochondrial transfer, such as CD38, could present a novel avenue for elimination of minimal residual disease in treatment for leukaemia [161]. Other promising mitochondrial-targeted approaches have been extensively reviewed elsewhere [162].…”

Section: Emerging Therapies: Immunotherapies and Mitochondrial-targetmentioning

confidence: 99%

Therapeutic Targeting of the Leukaemia Microenvironment

Kuek

Hughes

Kotecha

et al. 2021

IJMS

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In recent decades, the conduct of uniform prospective clinical trials has led to improved remission rates and survival for patients with acute myeloid leukaemia and acute lymphoblastic leukaemia. However, high-risk patients continue to have inferior outcomes, where chemoresistance and relapse are common due to the survival mechanisms utilised by leukaemic cells. One such mechanism is through hijacking of the bone marrow microenvironment, where healthy haematopoietic machinery is transformed or remodelled into a hiding ground or “sanctuary” where leukaemic cells can escape chemotherapy-induced cytotoxicity. The bone marrow microenvironment, which consists of endosteal and vascular niches, can support leukaemogenesis through intercellular “crosstalk” with niche cells, including mesenchymal stem cells, endothelial cells, osteoblasts, and osteoclasts. Here, we summarise the regulatory mechanisms associated with leukaemia–bone marrow niche interaction and provide a comprehensive review of the key therapeutics that target CXCL12/CXCR4, Notch, Wnt/b-catenin, and hypoxia-related signalling pathways within the leukaemic niches and agents involved in remodelling of niche bone and vasculature. From a therapeutic perspective, targeting these cellular interactions is an exciting novel strategy for enhancing treatment efficacy, and further clinical application has significant potential to improve the outcome of patients with leukaemia.

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Intercellular Mitochondrial Transfer in the Tumor Microenvironment

Cited by 32 publications

References 85 publications

Monoclonal Antibodies and Antibody Drug Conjugates in Multiple Myeloma

Monoclonal Antibodies and Antibody Drug Conjugates in Multiple Myeloma

SIRT1/PGC-1α/PPAR-γ Correlate With Hypoxia-Induced Chemoresistance in Non-Small Cell Lung Cancer

Therapeutic Targeting of the Leukaemia Microenvironment

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