Chemotherapy alters the increased numbers of myeloid-derived suppressor and regulatory T cells in children with acute lymphoblastic leukemia

Salem, Mohamed L.; El-Shanshory, Mohamed; Abdou, Said; Attia, Mohamed S.; Sobhy, Shymaa; Zidan, Mona; Zidan, Abdel‐Aziz A.

doi:10.1080/08923973.2018.1424897

Cited by 31 publications

(41 citation statements)

References 53 publications

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“…152 Also, acute lymphocytic leukemia patients treated with chemotherapeutic molecules have less suppressor cells, which contributes to a better prognosis. 153 Breast cancer patients expressing IL-17, and a STAT3 activated pathway, have less tumorinfiltrated MDSCs, 154 raising possibilities to target IL-17 as a therapeutic alternative. Altogether, these studies highlight the importance of studying immunosuppressive cell populations as targets of therapeutic alternatives against cancer.…”

Section: Evasion Of the Immune Response: Aberrant Communication Betwementioning

confidence: 99%

Tumor-induced neurogenesis and immune evasion as targets of innovative anti-cancer therapies

Cervantes‐Villagrana

Albores-García

Cervantes-Villagrana

et al. 2020

Sig Transduct Target Ther

161

112

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Normal cells are hijacked by cancer cells forming together heterogeneous tumor masses immersed in aberrant communication circuits that facilitate tumor growth and dissemination. Besides the well characterized angiogenic effect of some tumor-derived factors; others, such as BDNF, recruit peripheral nerves and leukocytes. The neurogenic switch, activated by tumor-derived neurotrophins and extracellular vesicles, attracts adjacent peripheral fibers (autonomic/sensorial) and neural progenitor cells. Strikingly, tumor-associated nerve fibers can guide cancer cell dissemination. Moreover, IL-1β, CCL2, PGE 2 , among other chemotactic factors, attract natural immunosuppressive cells, including T regulatory (Tregs), myeloid-derived suppressor cells (MDSCs), and M2 macrophages, to the tumor microenvironment. These leukocytes further exacerbate the aberrant communication circuit releasing factors with neurogenic effect. Furthermore, cancer cells directly evade immune surveillance and the antitumoral actions of natural killer cells by activating immunosuppressive mechanisms elicited by heterophilic complexes, joining cancer and immune cells, formed by PD-L1/PD1 and CD80/CTLA-4 plasma membrane proteins. Altogether, nervous and immune cells, together with fibroblasts, endothelial, and bone-marrow-derived cells, promote tumor growth and enhance the metastatic properties of cancer cells. Inspired by the demonstrated, but restricted, power of anti-angiogenic and immune cell-based therapies, preclinical studies are focusing on strategies aimed to inhibit tumor-induced neurogenesis. Here we discuss the potential of anti-neurogenesis and, considering the interplay between nervous and immune systems, we also focus on anti-immunosuppression-based therapies. Small molecules, antibodies and immune cells are being considered as therapeutic agents, aimed to prevent cancer cell communication with neurons and leukocytes, targeting chemotactic and neurotransmitter signaling pathways linked to perineural invasion and metastasis.

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Section: Evasion Of the Immune Response: Aberrant Communication Betwementioning

confidence: 99%

Tumor-induced neurogenesis and immune evasion as targets of innovative anti-cancer therapies

Cervantes‐Villagrana

Albores-García

Cervantes-Villagrana

et al. 2020

Sig Transduct Target Ther

161

112

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“…Initially, the most important aim of our study was to confirm the observation of an increased percentage of Treg cells in the bone marrow and/or peripheral blood of patients with acute leukemia made by other researchers [ 1 , 6 , 11 , 13 , 18 ].…”

Section: Discussionmentioning

confidence: 63%

“…ALL is one of the most common childhood cancer with favorable prognosis. Less than 20% of children with acute lymphoblastic leukemia have unfavourable prognosis and suffer from a relapse, resistant ALL, or serious complication of the chemotherapy [ 13 ]. For children with recurrent or refractory leukemia, new therapeutic options based on molecular biology and immunological therapy must be found to avoid serious and mortal complications caused by a high-dose chemo- and radiotherapy [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

CD4⁺CD25^highCD127^low/−FoxP₃⁺ Regulatory T Cell Subpopulations in the Bone Marrow and Peripheral Blood of Children with ALL: Brief Report

Niedźwiecki

Budziło

Zieliński

et al. 2018

Journal of Immunology Research

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CD4+CD25highCD127low/−FoxP3+ regulatory T cells (Tregs) are currently under extensive investigation in childhood acute lymphoblastic leukemia (ALL) and in other human cancers. Usually, Treg cells maintain the immune cell homeostasis. This small subset of T cells has been, in fact, considered to be involved in the pathogenesis of autoimmune diseases and progression of acute and chronic leukemias. However, whether Treg dysregulation in CLL and ALL plays a key role or it rather represents a simple epiphenomenon is still a matter of debate. Treg cells have been proposed as a prognostic indicator of the clinical course of the disease and might also be used for targeted immune therapy. Our study revealed statistically higher percentage of Treg cells in the bone marrow than in peripheral blood in the group of 42 children with acute lymphoblastic leukemia. By analyzing Treg subpopulations, it was shown that only memory Tregs in contact with leukemic antigens showed statistically significant differences. We noticed a low negative correlation between Treg cells in the bone marrow and the percentage of blasts (R = −0.36) as well as a moderate correlation between Treg cells in the bone marrow and Hb level (R = +0.41) in peripheral blood before therapy. The number of peripheral blood blasts on day 8th correlates negatively (R = −0.36) with Tregs. Furthermore, statistical analysis revealed low negative correlation between the number of Tregs in the bone marrow and the minimal residual disease measured on day 15th, the percentage of blasts in the bone marrow and leukocytosis after 15 days of chemotherapy. These results indicate the influence of Tregs on the final therapeutic effect.

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“…CD33 is transmembrane receptor expressed on cells of myeloid lineage and is usually considered to be myeloid specific . FCM analysis showed that CD33 expression was reduced in the CRT siRNA‐transfected HL‐60 cells compared to controls (51.21% vs 93.47%, respectively; Figure B).…”

Section: Resultsmentioning

confidence: 99%

Diallyl disulfide down‐regulates calreticulin and promotes C/EBPα expression in differentiation of human leukaemia cells

Sun

et al. 2018

J Cellular Molecular Medi

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Diallyl disulfide (DADS), the main active component of the cancer fighting allyl sulfides found in garlic, has shown potential as a therapeutic agent in various cancers. Previous studies showed DADS induction of HL‐60 cell differentiation involves down‐regulation of calreticulin (CRT). Here, we investigated the mechanism of DADS‐induced differentiation of human leukaemia cells and the potential involvement of CRT and CCAAT enhancer binding protein‐α (C/EBPα). We explored the expression of CRT and C/EBPα in clinical samples (20 healthy people and 19 acute myeloid leukaemia patients) and found that CRT and C/EBPα expressions were inversely correlated. DADS induction of differentiation of HL‐60 cells resulted in down‐regulated CRT expression and elevated C/EBPα expression. In severe combined immunodeficiency mice injected with HL‐60 cells, DADS inhibited the growth of tumour tissue and decreased CRT levels and increased C/EBPα in vivo. We also found that DADS‐mediated down‐regulation of CRT and up‐regulation of C/EBPα involved enhancement of reactive oxidative species. RNA immunoprecipitation revealed that CRT bound C/EBPα mRNA, indicating its regulation of C/EBPα mRNA degradation by binding the UG‐rich element in the 3′ untranslated region of C/EBPα. In conclusion, the present study demonstrates the C/EBPα expression was correlated with CRT expression in vitro and in vivo and the molecular mechanism of DADS‐induced leukaemic cell differentiation.

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Chemotherapy alters the increased numbers of myeloid-derived suppressor and regulatory T cells in children with acute lymphoblastic leukemia

Abstract: Our results indicate that B-ALL patients harbor high numbers of both MDSCs and T cells. This pilot study opens a new avenue to investigate the mechanism mediating the emergence of these cells on larger number of B-ALL patients at different treatment stages.

Cited by 31 publications

References 53 publications

Tumor-induced neurogenesis and immune evasion as targets of innovative anti-cancer therapies

Tumor-induced neurogenesis and immune evasion as targets of innovative anti-cancer therapies

CD4⁺CD25^highCD127^low/−FoxP₃⁺ Regulatory T Cell Subpopulations in the Bone Marrow and Peripheral Blood of Children with ALL: Brief Report

Diallyl disulfide down‐regulates calreticulin and promotes C/EBPα expression in differentiation of human leukaemia cells

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Chemotherapy alters the increased numbers of myeloid-derived suppressor and regulatory T cells in children with acute lymphoblastic leukemia

Abstract: Our results indicate that B-ALL patients harbor high numbers of both MDSCs and T cells. This pilot study opens a new avenue to investigate the mechanism mediating the emergence of these cells on larger number of B-ALL patients at different treatment stages.

Cited by 31 publications

References 53 publications

Tumor-induced neurogenesis and immune evasion as targets of innovative anti-cancer therapies

Tumor-induced neurogenesis and immune evasion as targets of innovative anti-cancer therapies

CD4+CD25highCD127low/−FoxP3+ Regulatory T Cell Subpopulations in the Bone Marrow and Peripheral Blood of Children with ALL: Brief Report

Diallyl disulfide down‐regulates calreticulin and promotes C/EBPα expression in differentiation of human leukaemia cells

Contact Info

Product

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CD4⁺CD25^highCD127^low/−FoxP₃⁺ Regulatory T Cell Subpopulations in the Bone Marrow and Peripheral Blood of Children with ALL: Brief Report