scholarly journals Multifunctional silica nanocomposites prime tumoricidal immunity for efficient cancer immunotherapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Linnan Yang ◽  
Feng Li ◽  
Yongsheng Cao ◽  
Qiang Liu ◽  
Guoxin Jing ◽  
...  
Keyword(s):  
Immune Response ◽  
Tumor Growth ◽  
Cancer Immunotherapy ◽  
Antitumor Immunity ◽  
Malignant Tumors ◽  
Mesoporous Silica Nanoparticles ◽  
Cancer Cell Line ◽  
Cervical Cancer Cell Line ◽  
Silica Nanocomposites ◽  
Molecular Patterns

AbstractThe tumor immune microenvironment (TIME) has been demonstrated to be the main cause of cancer immunotherapy failure in various malignant tumors, due to poor immunogenicity and existence of immunosuppressive factors. Thus, establishing effective treatments for hostile TIME remodeling has considerable potential to enhance immune response rates for durable tumor growth retardation. This study aims to develop a novel nanocomposite, polyethyleneimine-modified dendritic mesoporous silica nanoparticles loaded with microRNA-125a (DMSN-PEI@125a) to synergistically enhance immune response and immunosuppression reversion, ultimately generating a tumoricidal environment. Our results showed that DMSN-PEI@125a exhibited excellent ability in cellular uptake by murine macrophages and the cervical cancer cell line TC-1, repolarization of tumor associated macrophages (TAMs) to M1 type in a synergistic manner, and promotion of TC-1 immunogenic death. Intratumor injection of DMSN-PEI@125a facilitated the release of more damage-related molecular patterns and enhanced the infiltration of natural killer and CD8+ T cells. Meanwhile, repolarized TAMs could function as a helper to promote antitumor immunity, thus inhibiting tumor growth in TC-1 mouse models in a collaborative manner. Collectively, this work highlights the multifunctional roles of DMSN-PEI@125a in generating an inflammatory TIME and provoking antitumor immunity, which may serve as a potential agent for cancer immunotherapy.

Rediscovery of Nanoparticle-based Therapeutics: Boosting Immunogenic Cell Death for Potential Application in Cancer Immunotherapy

2021 ◽  
Author(s):  
Suah Yang ◽  
In-Cheol Sun ◽  
Hee Sook Hwang ◽  
Man Kyu Shim ◽  
Hong Yeol Yoon ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Cancer Immunotherapy ◽  
Potential Application ◽  
Adaptive Immune Response ◽  
Immunogenic Cell Death ◽  
Living Body ◽  
Adaptive Immune ◽  
Physical Stimuli ◽  
Molecular Patterns

Immunogenic cell death (ICD) occurred by chemical and physical stimuli has shown the potential to activate an adaptive immune response in the immune-competent living body through releasing danger-associated molecular patterns...

scholarly journals Overexpression of the nucleoporin Nup88 stimulates migration and invasion of HeLa cells

2021 ◽  
Author(s):  
Masaki Makise ◽  
Ryota Uchimura ◽  
Kumiko Higashi ◽  
Yasumi Mashiki ◽  
Rikako Shiraishi ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cell ◽  
Hela Cells ◽  
Malignant Tumors ◽  
Cancer Cell Line ◽  
Migration And Invasion ◽  
Nuclear Pore ◽  
Cervical Cancer Cell Line ◽  
Invasive Ability ◽  
Mesenchymal Transition

AbstractElevated expression of the nucleoporin Nup88, a constituent of the nuclear pore complex, is seen in various types of malignant tumors, but whether this overexpression contributes to the malignant phenotype has yet to be determined. Here, we investigated the effect of the overexpression of Nup88 on the migration and invasion of cervical cancer HeLa cells. The overexpression of Nup88 promoted a slight but significant increase in both migration and invasion, whereas knockdown of Nup88 by RNA interference suppressed these phenotypes. The observed phenotypes in Nup88-overexpressing HeLa cells were not due to the progression of the epithelial-to-mesenchymal transition or activation of NF-κB, which are known to be important for cell migration and invasion. Instead, we identified an upregulation of matrix metalloproteinase-12 (MMP-12) at both the gene and protein levels in Nup88-overexpressing HeLa cells. Upregulation of MMP-12 protein by the overexpression of Nup88 was also observed in one other cervical cancer cell line and two prostate cancer cell lines but not 293 cells. Treatment with a selective inhibitor against MMP-12 enzymatic activity significantly suppressed the invasive ability of HeLa cells induced by Nup88 overexpression. Taken together, our results suggest that overexpression of Nup88 can stimulate malignant phenotypes including invasive ability, which is promoted by MMP-12 expression.

IMMUNOLOGICAL CHANGES IN PATIENTS WITH MALIGNANT TUMORS AFTER CRYOGENIC AND ULTRASONIC ABLATION OF A TUMOR

2017 ◽  
Vol 63 (1) ◽  
pp. 14-18
Author(s):  
Aleksey Belyaev ◽  
Irina Baldueva ◽  
Georgiy Prokhorov ◽  
Denis Prokhorov ◽  
Natalya Yemelyanova
Keyword(s):  
Immune Response ◽  
Clinical Trials ◽  
Animal Models ◽  
Minimally Invasive ◽  
Antitumor Immunity ◽  
Malignant Tumors ◽  
Experimental Animal Models ◽  
Minimally Invasive Surgical ◽  
Tumor Focus ◽  
Immunological Changes

Studies on experimental animal models and clinical trials indicate that cryosurgery of tumor focus leads to the activation of antitumor immunity. Systematic minimally invasive surgical impact on the primary tumor or its metastases, causing a pronounced immune response, becomes an actual task of modern oncology.

scholarly journals Necrotic debris and STING exert therapeutically relevant effects on tumor cholesterol homeostasis

2022 ◽  
Vol 5 (3) ◽  
pp. e202101256
Author(s):  
Sampath Katakam ◽  
Santosh Anand ◽  
Patricia Martin ◽  
Nicolo Riggi ◽  
Ivan Stamenkovic
Keyword(s):  
Tumor Growth ◽  
Cyclic Gmp ◽  
Malignant Tumors ◽  
Underlying Mechanism ◽  
Major Effect ◽  
Cholesterol Homeostasis ◽  
Synthesis Inhibitor ◽  
Molecular Patterns ◽  
Dying Cells ◽  
Necrotic Debris

Malignant tumors commonly display necrosis, which invariably triggers an inflammatory response that supports tumor growth. However, the effect on tumor cells of necrotic debris, or damage-associated molecular patterns (DAMPs) released by dying cells is unknown. Here, we addressed the effect of DAMPs on primary Ewing sarcoma (EwS) cells and cell lines grown in 3D (spheroids) and 2D culture. We show that DAMPs promote the growth of EwS spheroids but not 2D cultures and that the underlying mechanism implicates an increase in cholesterol load in spheroids. In contrast, stimulation of the nucleic acid sensor signaling platform STING by its ligand cyclic GMP-AMP decreases the tumor cell cholesterol load and reduces their tumor initiating ability. Overexpression of STING or stimulation with cyclic GMP-AMP opposes the growth stimulatory effect of DAMPs and synergizes with the cholesterol synthesis inhibitor simvastatin to inhibit tumor growth. Our observations show that modulation of cholesterol homeostasis is a major effect of necrotic cell debris and STING and suggest that combining STING agonists with statins may help control tumor growth.

scholarly journals Targeting the interleukin-17 immune axis for cancer immunotherapy

2019 ◽  
Vol 217 (1) ◽  
Author(s):  
Gerardo A. Vitiello ◽  
George Miller
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Cancer Immunotherapy ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Antitumor Immunity ◽  
Interleukin 17 ◽  
Cell Immunotherapy ◽  
Insight Into

The role of IL-17 in cancer remains controversial. Emerging evidence suggests that during early oncogenesis IL-17 supports tumor growth, whereas in established tumors IL-17 production by γδ and Th17 cells potentiates antitumor immunity. Consequently, γδ and Th17 cells are attractive targets for immunotherapy in the IL-17 immune axis. To optimize IL-17–based immunotherapy, a deeper understanding of the cytokines dictating IL-17 production and the polarity of γδ and Th17 cells is critical. Here, we delve into the dichotomous roles of IL-17 in cancer and provide insight into the tumor microenvironment conducive for successful IL-17–based γδ and Th17 cell immunotherapy.

Inhibition of tumor growth in a murine xenograft model by thalidomide

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 20083-20083
Author(s):  
L. Horn ◽  
M. Hermes ◽  
J. Schwock ◽  
M. Brulport ◽  
J. G. Hengstler
Keyword(s):  
Cervical Cancer ◽  
Tumor Growth ◽  
Tumor Volume ◽  
Xenograft Model ◽  
Cancer Cell Line ◽  
Cervical Cancer Cell Line ◽  
Tumor Diameter ◽  
Murine Xenograft Model ◽  
Inhibition Of Tumor Growth ◽  
The Mean

20083 Background: Limitations in the treatment of recurrent disease in cervical carcinoma are for radiation therapy large tumor size and pelvic side wall involvement and for exenteration procedurde previous radiation therapy, bulky disease, and others. Alternative approaches including chemotherapy, chemo-radiation, radiation plus hyperthermia and others are accompanied by a failure rate of 50 to 80%. Recent research has shown that the antineoplastic effect of thalidomide (TD) is due to the inhibition of neo-angiogenesis, a decrease of TNF-a, blocking of nuclear factor κβ-kinase activity, stimulation of the IL-2 and downregulation of cell adhesion molecules. Here, we have studied the effect of TD on a cervical cancer cell line in a murine xenograft model. Methods: We injected 7 × 106 HELA cells s.c. into the dorsal skin of 6–8 week-old male nude mice (cd nu−/nu−; Charles River, Sulzfeld, Germany). The tumor diameter was measured with a caliber rule. The maximum and minimum diameters of the tumor were determined. Tumor volume (V) was calculated by the formula: V = a × b × b/2, where a represents the minimum and b the maximum tumor diameter. As soon as tumors reached a volume of 0.25 cm3 the mice were randomized into a treatment (n = 9) and a control group (n = 9). The mice in the treatment group received 14 daily injections of 300 mg/kg (i.p.) thalidomide for 14 days. Animals were housed under specific pathogen-free conditions. The experiments have been approved by the local animal welfare committee. Results: Thalidomide caused a clear delay in tumor growth. Already 7 days after onset of thalidomide therapy the mean tumor volume was smaller in the treated (0.24 ± 0.03 cm3) compared to the control mice (0.73 ± 0.15 cm3; mean ± standard error; p < 0.01). After 14 days of thalidomide treatment the mean tumor volumes were 0.37 ± 0.05 and 1.05 ± 0.19 cm3 in the treated and in the control mice, respectively (p < 0.01). However, after the end of the 14 days treatment period a new onset of tumor growth was observed. In conclusion, thalidomide delayed tumor growth but did not cause tumor remission. Conclusions: TD is effective in inhibition of tumor growth of a cervical cancer cell line in a mouse xenograft model and might be an alternative drug in patients with recurrent cervical carcinoma without any options for established standard therapy. No significant financial relationships to disclose.

scholarly journals Future of cancer immunotherapy using plant virus-based nanoparticles

2019 ◽  
Vol 5 (7) ◽  
pp. FSO401 ◽  
Author(s):  
Erum Shoeb ◽  
Kathleen Hefferon
Keyword(s):  
Immune Response ◽  
Cancer Immunotherapy ◽  
Plant Virus ◽  
Malignant Tumors ◽  
Plant Viruses ◽  
The Body ◽  
Special Report ◽  
Drug Delivery Vehicles ◽  
Computer Based ◽  
Delivery Vehicles

Immunotherapy potentiates a patient’s immune response against some forms of cancer, including malignant tumors. In this Special Report, we have summarized the use of nanoparticles that have been designed for use in cancer immunotherapy with particular emphasis on plant viruses. Plant virus-based nanoparticles are an ideal choice for therapeutic applications, as these nanoparticles are not only capable of targeting the desired cells but also of being safely delivered to the body without posing any threat of infection. Plant viruses can be taken up by tumor cells and can be functionalized as drug delivery vehicles. This Special Report describes how the future of cancer immunotherapy could be a success through the merger of computer-based technology using plant-virus nanoparticles.

JAML promotes CD8 and γδ T cell antitumor immunity and is a novel target for cancer immunotherapy

2021 ◽  
Vol 218 (10) ◽  
Author(s):  
Joseph M. McGraw ◽  
Flavian Thelen ◽  
Eric N. Hampton ◽  
Nelson E. Bruno ◽  
Travis S. Young ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Growth ◽  
Cancer Immunotherapy ◽  
Antitumor Immunity ◽  
Tumor Infiltrating Lymphocytes ◽  
Tissue Loss ◽  
Mouse Tumor ◽  
Novel Target ◽  
Adenovirus Receptor ◽  
Infiltrating Lymphocytes

T cells are critical mediators of antitumor immunity and a major target for cancer immunotherapy. Antibody blockade of inhibitory receptors such as PD-1 can partially restore the activity of tumor-infiltrating lymphocytes (TILs). However, the activation signals required to promote TIL responses are less well characterized. Here we show that the antitumor activity of CD8 and γδ TIL is supported by interactions between junctional adhesion molecule–like protein (JAML) on T cells and its ligand coxsackie and adenovirus receptor (CXADR) within tumor tissue. Loss of JAML through knockout in mice resulted in accelerated tumor growth that was associated with an impaired γδ TIL response and increased CD8 TIL dysfunction. In mouse tumor models, therapeutic treatment with an agonistic anti-JAML antibody inhibited tumor growth, improved γδ TIL activation, decreased markers of CD8 TIL dysfunction, and significantly improved response to anti–PD-1 checkpoint blockade. Thus, JAML represents a novel therapeutic target to enhance both CD8 and γδ TIL immunity.

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