Irradiation-induced localization of IL-12-expressing mesenchymal stem cells to enhance the curative effect in murine metastatic hepatoma

Jeong, Keun‐Yeong; Lee, Eun Jung; Kim, Su Jin; Yang, Seung‐Hyun; Sung, Young Chul; Seong, Jinsil

doi:10.1002/ijc.29428

Cited by 30 publications

(22 citation statements)

References 32 publications

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“…Besides being part of the GBM microenvironment [28], MSCs have been suggested as therapeutic vectors for cellular therapy of GBM [23–30], but such treatment is still not approved due to observed opposite effects of MSCs on the same type of tumors in vivo and in vitro [28, 38]. However, here we show for the first time that the reason for the opposite effect is also the heterogeneity of GBM cells, highly relevant for an overall response of infiltrated and/or exogenously applied MSCs into the tumor.…”

Section: Discussionmentioning

confidence: 99%

“…MSCs are increasingly used in cell therapies and tissue engineering because of their availability, multi-potency, and immunomodulatory activity [22]. Recruited bone marrow-derived MSCs can home neoplasia and become part of the tumor microenvironment [23–26], including GBM [27], but seem to have dual roles in tumors, which mainly depend on their immuno-activation status [28]. In glioma, both roles of MSCs in promotion [24, 26] and inhibition of tumor growth have been reported [26–30].…”

Section: Introductionmentioning

confidence: 99%

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Mesenchymal stem cells differentially affect the invasion of distinct glioblastoma cell lines

et al. 2017

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Glioblastoma multiforme are an aggressive form of brain tumors that are characterized by distinct invasion of single glioblastoma cells, which infiltrate the brain parenchyma. This appears to be stimulated by the communication between cancer and stromal cells. Mesenchymal stem cells (MSCs) are part of the glioblastoma microenvironment, and their ‘cross-talk’ with glioblastoma cells is still poorly understood. Here, we examined the effects of bone marrow-derived MSCs on two different established glioblastoma cell lines U87 and U373. We focused on mutual effects of direct MSC/glioblastoma contact on cellular invasion in three-dimensional invasion assays in vitro and in a zebrafish embryo model in vivo. This is the first demonstration of glioblastoma cell-type-specific responses to MSCs in direct glioblastoma co-cultures, where MSCs inhibited the invasion of U87 cells and enhanced the invasion of U373. Inversely, direct cross-talk between MSCs and both of glioblastoma cell lines enhanced MSC motility. MSC-enhanced invasion of U373 cells was assisted by overexpression of proteases cathepsin B, calpain1, uPA/uPAR, MMP-2, -9 and -14, and increased activities of some of these proteases, as determined by the effects of their selective inhibitors on invasion. In contrast, these proteases had no effect on U87 cell invasion under MSC co-culturing. Finally, we identified differentially expressed genes, in U87 and U373 cells that could explain different response of these cell lines to MSCs. In conclusion, we demonstrated that MSC/glioblastoma cross-talk is different in the two glioblastoma cell phenotypes, which contributes to tumor heterogeneity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cells differentially affect the invasion of distinct glioblastoma cell lines

et al. 2017

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“…Balyasnika et al , showed TRAIL expressing MSCs in combination with irradiation promoted survival rate in brain tumor bearing mice42. More recently, it has been shown that irradiation enhanced curative effects of IL-12 expressing MSCs in murine metastatic hepatoma by inducing MSCs localization and increasing apoptotic activity43. Radiotherapy enhanced tumor cell sensitivity to TRAIL by inducing expression of DR-4/DR-5 in human or DR-5 in mice confirmed in wide range of tumor such as lung, colon, head and neck, prostate and breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Irradiation enhances susceptibility of tumor cells to the antitumor effects of TNF-α activated adipose derived mesenchymal stem cells in breast cancer model

Mohammadpour

Pourfathollah

Zarif

et al. 2016

Sci Rep

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Gene modified or cytokine activated mesenchymal stem cells (MSCs) have been used as a treatment in various types of cancer. Moreover, irradiation is usually applied as either a standard primary or adjuvant therapy. Here, we showed that the expression of TNF related apoptosis-inducing ligand (TRAIL) and Dickouf-3 (Dkk-3), the promising anticancer proteins, increased in murine adipose-derived mesenchymal stromal cells (AD-MSCs) following activation with TNF-α, resulting in the induction of apoptosis in cancer cells. Also, anticancer effects of TNF-α activated AD-MSCs were intensified with irradiation. In vivo results showed that TNF-α preactivated AD-MSCs combined with irradiation decreased tumor size and increased survival rate in tumor bearing mice. On the other hands, both TNF-α preactivated AD-MSCs with or without irradiation prevented metastasis in ling and liver, and increased apoptosis in tumor mass. Finally, flowcytometry assay demonstrated that naïve AD-MSCs combined with irradiation but not TNF-α activated MSCs with irradiation increased Treg population in lymph node and spleen. Altogether, obtained results suggest that TNF-α activated MSCs combined with irradiation therapy can serve as new strategy in breast cancer therapy.

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“…These include modification to produce immunostimulatory cytokines (e.g. IFN-α, IFN-β, IL-12) and T cell trafficking molecules such as LIGHT [50][51][52][53].…”

Section: Strategies To Counteract Adaptive Resistance To Immune Checkmentioning

confidence: 99%

Immune Checkpoint Blockade and Adaptive Immune Resistance in Cancer

Wong¹,

Cameron²

2017

Immunotherapy - Myths, Reality, Ideas, Future

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The clinical success of immune checkpoint blockers is a pivotal advancement for treating an increasing number of cancer types. However, immune checkpoint blockers still rarely induce complete remission and show little to no therapeutic efficacy in a significant percentage of cancer patients. Efforts are now underway to identify biomarkers that accurately predict which patients benefit from immune checkpoint blockers. Moreover, adaptive immune resistance can develop in tumors during treatment with immune checkpoint blockers. These adaptive resistance mechanisms in tumors might be disrupted by combining adjunctive immunotherapies, which could potentially improve the therapeutic efficacy of immune checkpoint blockers. This chapter discusses the mechanism of action of cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed death-1/ programmed death-ligand 1 (PD-1/PD-L1) immune checkpoint blockers and biomarkers that might predict clinical responses to these drugs. Lastly, ongoing research on mechanisms of tumor adaptive resistance could facilitate rationale design of adjunctive immunotherapies that can be synergistically combined with immune checkpoint blockers to more effectively treat cancer.

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Irradiation-induced localization of IL-12-expressing mesenchymal stem cells to enhance the curative effect in murine metastatic hepatoma

Cited by 30 publications

References 32 publications

Mesenchymal stem cells differentially affect the invasion of distinct glioblastoma cell lines

Mesenchymal stem cells differentially affect the invasion of distinct glioblastoma cell lines

Irradiation enhances susceptibility of tumor cells to the antitumor effects of TNF-α activated adipose derived mesenchymal stem cells in breast cancer model

Immune Checkpoint Blockade and Adaptive Immune Resistance in Cancer

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