Senescent stromal cell-induced divergence and therapeutic resistance in T cell acute lymphoblastic leukemia/lymphoma

Habiel, David M.; Krepostman, Nicolas; Lilly, Michael B.; Cavassani, Karen A.; Coelho, Ana Lúcia; Shibata, Takehiko; Elenitoba-Johnson, Kojo S.J.; Hogaboam, Cory M.

doi:10.18632/oncotarget.13158

Cited by 18 publications

(14 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To assess the binding of AD-114-6H to lung tissue associated CXCR4, IHC staining with AD-114-6H was initially optimized on spleen and liver tissue from immunocompromised SCID/bg mice that had been challenged with an intravenous injection of CXCR4-expressing human leukemic T cells, CCRF-CEM cells, ( 27 , 34 – 36 ) ( Figure S2 ) . AD-114 immunolabeled few cells in NDC lung explants (Fig.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Anti-fibrotic Effects of CXCR4-Targeting i-body AD-114 in Preclinical Models of Pulmonary Fibrosis

Griffiths

Habiel

Jaffar

et al. 2018

Sci Rep

View full text Add to dashboard Cite

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease that is prevalent in individuals >50 years of age, with a median survival of 3–5 years and limited therapeutic options. The disease is characterized by collagen deposition and remodeling of the lung parenchyma in a process that is thought to be driven by collagen-expressing immune and structural cells. The G-protein coupled C-X-C chemokine receptor 4, CXCR4, is a candidate therapeutic target for IPF owing to its role in the recruitment of CXCR4+ fibrocytes from the bone marrow to fibrotic lung tissue and its increased expression levels by structural cells in fibrotic lung tissue. We have engineered a novel fully human single domain antibody “i-body” called AD-114 that binds with high affinity to human CXCR4. We demonstrate here that AD-114 inhibits invasive wound healing and collagen 1 secretion by human IPF fibroblasts but not non-diseased control lung fibroblasts. Furthermore, in a murine bleomycin model of pulmonary fibrosis, AD-114 reduced the accumulation of fibrocytes (CXCR4+/Col1+/CD45+) in fibrotic murine lungs and ameliorated the degree of lung injury. Collectively, these studies demonstrate that AD-114 holds promise as a new biological therapeutic for the treatment of IPF.

show abstract

Section: Resultsmentioning

confidence: 99%

“…SCID/Bg mice were intravenously administered with CCRF-CEM cells as previously described 36 . Mice were sacrificed 25–27 days after cellular administration and their spleens and livers were fixed, paraffin embedded, sectioned and stained with AD-114-6H or control i-body.…”

Section: Methodsmentioning

confidence: 99%

Anti-fibrotic Effects of CXCR4-Targeting i-body AD-114 in Preclinical Models of Pulmonary Fibrosis

Griffiths

Habiel

Jaffar

et al. 2018

Sci Rep

View full text Add to dashboard Cite

show abstract

“…In a recent study that investigates the mechanisms of therapy resistance observed in T‐cell acute lymphoblastic leukemia/lymphoma (T‐ALL/LBL), a fibrotic signature was detected in cancer cells . The data indicated that senescent rather than proliferating stromal cells induced such a signature in malignant cells, partially due to the enhanced production of oxidative radicals and EVs containing miRNAs that target BRCA1 and the mismatch repair (MMR) pathway components .…”

Section: Therapeutic Resistance Can Be Conferred By Evs Of Stromal Cementioning

confidence: 99%

Extracellular vesicles in the tumor microenvironment: Therapeutic resistance, clinical biomarkers, and targeting strategies

Han

et al. 2017

Medicinal Research Reviews

View full text Add to dashboard Cite

Numerous studies have proved that cell‐nonautonomous regulation of neoplastic cells is a distinctive and essential characteristic of tumorigenesis. Two way communications between the tumor and the stroma, or within the tumor significantly influence disease progression and modify treatment responses. In the tumor microenvironment (TME), malignant cells utilize paracrine signaling initiated by adjacent stromal cells to acquire resistance against multiple types of anticancer therapies, wherein extracellular vesicles (EVs) substantially promote such events. EVs are nanoscaled particles enclosed by phospholipid bilayers, and can mediate intercellular communications between cancerous cells and the adjacent microenvironment to accelerate pathological proceeding. Here we review the most recent studies of EV biology and focus on key cell lineages of the TME and their EV cargoes that are biologically active and responsible for cancer resistance, including proteins, RNAs, and other potentially essential components. Since EVs are emerging as novel but critical elements in establishing and maintaining hallmarks of human cancer, timely and insightful understanding of their molecular properties and functional mechanisms would pave the road for clinical diagnosis, prognosis, and effective targeting in the global landscape of precision medicine. Further, we address the potential of EVs as promising biomarkers in cancer clinics and summarize the technical improvements in EV preparation, analysis, and imaging. We highlight the practical issues that should be exercised with caution to guide the development of targeting agents and therapeutic methodologies to minimize cancer resistance driven by EVs, thereby allowing to effectively control the early steps of disease exacerbation.

show abstract

“…Acute lymphoblastic leukemia (ALL) is an aggressive neoplasia characterized by the uncontrolled proliferation of aberrant lymphocytes, and represents the most common childhood cancer [ 1 – 3 ]. Over years, several efforts have been made for the best treatment approach, such as combination of chemotherapy and radiotherapy [ 4 , 5 ]. These therapies, however, may impair the whole child health status and quality of life through different side effects which include osteopenia, muscle atrophy, cardiovascular and cardiopulmonary problems or metabolism alterations [ 6 – 9 ].…”

Section: Introductionmentioning

confidence: 99%

Physical training interventions for children and teenagers affected by acute lymphoblastic leukemia and related treatment impairments

et al. 2018

View full text Add to dashboard Cite

A decreased physical fitness has been reported in patients and survivors of acute lymphoblastic leukemia (ALL). This is influenced by the negative effects of the disease and by the treatments of childhood cancer.In the past, children were advised to recover in bed, and to take as much relax as possible. Nowadays, it is considered that too much immobility may result in a further decrease of physical fitness and functioning. Exercise training for ALL children has frequently been reported to improve physical fitness and the well-being of the children, since it prevents the negative effects of a sedentary life-style, such as obesity and a poor skeletal health. In recent years, different studies and protocols on this subject has become available for children and young adults with cancer, both during and after treatment.The efficacy of recent physical exercise training interventions, that act on several ALL impairments in children such as skeletal, musculoskeletal, neuromuscular, cardiopulmonary and cardiovascular systems, fatigue, body balance disorders and metabolism alterations have been examined.These side effects might be prevented or significantly reduced by introducing a physical exercise program during or shortly after cancer treatment. Several interventions are discussed and presented for each impairment, reducing their level caused by the disease and thus suggesting the importance of physical training activity in ameliorating the children quality of life.

show abstract

Senescent stromal cell-induced divergence and therapeutic resistance in T cell acute lymphoblastic leukemia/lymphoma

Cited by 18 publications

References 44 publications

Anti-fibrotic Effects of CXCR4-Targeting i-body AD-114 in Preclinical Models of Pulmonary Fibrosis

Anti-fibrotic Effects of CXCR4-Targeting i-body AD-114 in Preclinical Models of Pulmonary Fibrosis

Extracellular vesicles in the tumor microenvironment: Therapeutic resistance, clinical biomarkers, and targeting strategies

Physical training interventions for children and teenagers affected by acute lymphoblastic leukemia and related treatment impairments

Contact Info

Product

Resources

About