scholarly journals A tumor-microenvironment-responsive nanomaterial for cancer chemo-photothermal therapy

RSC Advances ◽  
2020 ◽  
Vol 10 (37) ◽  
pp. 22091-22101
Author(s):  
Kaiyu Wang ◽  
Zhiyuan Cai ◽  
Rong Fan ◽  
Qian Yang ◽  
Tao Zhu ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Tumor Microenvironment ◽  
Therapeutic Effect ◽  
Photothermal Therapy

Endogenous hydrogen peroxide was utilized to control the release of agents for better tumor therapeutic effect and safety.

Activatable UCL/CT/MR-Enhanced in vivo Imaging-Guided Radiotherapy and Photothermal Therapy

2022 ◽  
Author(s):  
Jianming Ni ◽  
Huiting Xu ◽  
Yanqi Zhong ◽  
Yongping Zhou ◽  
Shudong Hu
Keyword(s):  
Tumor Microenvironment ◽  
Therapeutic Effect ◽  
In Vivo Imaging ◽  
Photothermal Therapy ◽  
Copper Sulphide ◽  
Hypoxic Tumor

Although sophisticated radiotherapy (RT) technology has been widely applied in clinical oncotherapy, unsatisfactory therapeutic effect resulted by hypoxic tumor microenvironment and complications are still prevalent. Herein, copper sulphide nanoparticles (CuS...

scholarly journals A TLR4 agonist improves immune checkpoint blockade treatment by increasing the ratio of effector to regulatory cells within the tumor microenvironment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
A. Farias ◽  
A. Soto ◽  
F. Puttur ◽  
C. J. Goldin ◽  
S. Sosa ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Therapeutic Effect ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Combined Treatment ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Regulatory Cells ◽  
Ifn Γ

AbstractBrucella lumazine synthase (BLS) is a homodecameric protein that activates dendritic cells via toll like receptor 4, inducing the secretion of pro-inflammatory cytokines and chemokines. We have previously shown that BLS has a therapeutic effect in B16 melanoma-bearing mice only when administered at early stages of tumor growth. In this work, we study the mechanisms underlying the therapeutic effect of BLS, by analyzing the tumor microenvironment. Administration of BLS at early stages of tumor growth induces high levels of serum IFN-γ, as well as an increment of hematopoietic immune cells within the tumor. Moreover, BLS-treatment increases the ratio of effector to regulatory cells. However, all treated mice eventually succumb to the tumors. Therefore, we combined BLS administration with anti-PD-1 treatment. Combined treatment increases the outcome of both monotherapies. In conclusion, we show that the absence of the therapeutic effect at late stages of tumor growth correlates with low levels of serum IFN-γ and lower infiltration of immune cells in the tumor, both of which are essential to delay tumor growth. Furthermore, the combined treatment of BLS and PD-1 blockade shows that BLS could be exploited as an essential immunomodulator in combination therapy with an immune checkpoint blockade to treat skin cancer.

705 Anti-tumor activity of CB-668, a potent, selective and orally bioavailable small-molecule inhibitor of the immuno-suppressive enzyme Interleukin 4 (IL-4)-Induced Gene 1 (IL4I1)

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A747-A747
Author(s):  
Andrew MacKinnon ◽  
Deepthi Bhupathi ◽  
Jason Chen ◽  
Tony Huang ◽  
Weiqun Li ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Tumor Microenvironment ◽  
Immune Cell ◽  
Interleukin 4 ◽  
Mouse Tumor ◽  
Syngeneic Mouse ◽  
Molecule Inhibitor ◽  
Anti Tumor Activity ◽  
Mouse Tumor Models

BackgroundTumors evade destruction by the immune system through multiple mechanisms including altering metabolism in the tumor microenvironment. Metabolic control of immune responses occurs through depletion of essential nutrients or accumulation of toxic metabolites that impair immune cell function and promote tumor growth. The secreted enzyme interleukin 4 (IL-4)-induced gene 1 (IL4I1) is an L-phenylalanine oxidase that catabolizes phenylalanine and produces phenyl-pyruvate and hydrogen peroxide. IL4I1 regulates several aspects of adaptive immunity in mice, including inhibition of cytotoxic T cells through its production of hydrogen peroxide (reviewed in1). In human tumors, IL4I1 expression is significantly elevated relative to normal tissues and is notably high in ovarian tumors and B cell lymphomas. Motivated by the hypothesis that IL4I1 is an immuno-metabolic enzyme that suppresses anti-tumor immunity, we discovered CB-668, the first known small-molecule inhibitor of IL4I1.MethodsIL4I1 enzymatic activity was measured using an HRP-coupled enzyme assay. RNA in-situ hybridization was carried out on the RNAScope platform. Syngeneic mouse tumor models were used to evaluate the anti-tumor activity of CB-668. The level of phenyl-pyruvate in tumor homogenates was measured by LC/MS.ResultsOur clinical candidate, CB-668 is a potent and selective non-competitive inhibitor of IL4I1 (IC50 = 15 nM). CB-668 has favorable in vitro ADME properties and showed low clearance and high oral bioavailability in rodents. Twice-daily oral administration of CB-668 was well-tolerated in mice and resulted in single-agent anti-tumor activity in the syngeneic mouse tumor models B16-F10, A20, and EG7. Oral CB-668 administration reduced the levels of phenyl-pyruvate in the tumor, consistent with inhibition of IL4I1 enzymatic activity. Anti-tumor activity of CB-668 was immune cell-mediated since efficacy was abrogated in CD8-depleted mice, and CB-668 treatment caused increased expression of pro-inflammatory immune genes in the tumor. Moreover, CB-668 had no direct anti-proliferative activity on tumor cells grown in vitro (IC50 > 50 µM). CB-668 also favorably combined with anti-PD-L1 therapy to reduce tumor growth in the B16-F10 tumor model.ConclusionsThese data support an immune-mediated anti-tumor effect of IL4I1 inhibition by CB-668, and suggest inhibition of IL4I1 represents a novel strategy for cancer immuno-therapy.ReferencesMolinier-Frenkel V, Prévost-Blondel A, and Castellano F. The IL4I1 Enzyme: A New Player in the Immunosuppressive Tumor Microenvironment. Cells 2019;8:1–9.

scholarly journals P04.05 Modulating tumor microenvironment with arginase-1 specific T cells

2020 ◽  
Vol 8 (Suppl 2) ◽  
pp. A38.2-A39
Author(s):  
E Martinenaite ◽  
M Aaboe Joergensen ◽  
RE Johansson Mortensen ◽  
S Munir Ahmad ◽  
SE Weis-Banke ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Therapeutic Effect ◽  
Potential Role ◽  
Myeloid Cells ◽  
Tumor Site ◽  
Arginase 1 ◽  
Part Time

BackgroundCancer progression is associated with an increased immune suppression at the tumor site. Arginase-1 is an enzyme well-known for its involvement in metabolic immune regulation. At the tumor site, arginase-1 acts by reducing availability of L-arginine to the infiltrating immune cells thus reducing T cell functionality and proliferation. While arginase-1 is expressed by some tumor cells, it has also been shown to be produced by immune inhibitory myeloid cells, such as myeloid derived suppressor cells (MDSCs), tumor associated macrophages (TAMs) and is associated with poor prognosis. Previously, we demonstrated that spontaneous CD4+ and CD8+ T-cell immune responses against arginase-derived, HLA-restricted peptides can be found in both cancer patients and healthy individuals (Martinenaite et al, 2018, DOI: 10.1080/2162402X.2017.1404215). These T cells are present in the memory T cell compartment, and that they are activated in arginase-1 inducing conditions, such as presence of TH2 cytokines IL-4 or IL-13 in vitro (Martinenaite et al, 2019, DOI: 10.1038/s41423-019-0231-3 and DOI: 10.1007/s00262-019-02425-6).Methods and ResultsIn order to explore if arginase-1-specific T cells have a potential role in modulation of immune homeostasis, human arginase-1-specific memory T cells were isolated and expanded for functional characterization. We show that arginase-1-specific T cells specifically recognize arginase-1 expressing cells, such as mRNA transfected autologous dendritic cells (DCs) and B cells as well as M2 polarized macrophages in vitro. In addition, activated arginase-1-specific T cells produce pro-inflammatory cytokines IFNγ and TNFα. Secretion of TH1 cytokines by these T cells suggests potential role as potent immune modulators in the tumor microenvironment, since many arginase-1 expressing myeloid cells are not terminally differentiated and they can be re-polarized to an immunostimulatory, M1-like phenotype. We also observed that targeting of M2-polarized arginase-1 expressing monocytic leukemia cell line THP-1 with arginase-1-specific CD4+ T cells induces upregulation of PD-L1 on the THP-1 cells. Furthermore, we demonstrate that an arginase-1-derive peptide vaccine has a therapeutic effect in syngeneic mouse tumor models (B16 and MC38), both as monotherapy and in combination with anti-PD-1 treatment. The therapeutic effect was associated with increased immune infiltration in the peptide vaccinated mice compared to the control.ConclusionsOur study provides evidence that immune modulatory vaccination targeting arginase-1 is an intriguing way of targeting the immune suppressive microenvironment.Disclosure InformationE. Martinenaite: A. Employment (full or part-time); Significant; IO Biotech. M. Aaboe Joergensen: None. R.E. Johansson Mortensen: None. S. Munir Ahmad: None. S.E. Weis-Banke: None. M. Orebo Holmström: None. A. Wakatsuki Pedersen: A. Employment (full or part-time); Significant; IO Biotech. Ö. Met: None. I.M. Svane: F. Consultant/Advisory Board; Significant; IO Biotech. M. Hald Andersen: A. Employment (full or part-time); Significant; IO Biotech.

scholarly journals Development of tungsten bronze nanorods for redox-enhanced photoacoustic imaging-guided photothermal therapy of tumors

RSC Advances ◽  
2018 ◽  
Vol 8 (47) ◽  
pp. 26713-26719 ◽  
Author(s):  
Hongbo Gao ◽  
Xiangming Fang ◽  
Jing Xiang ◽  
Xiaohang Liu ◽  
JianPing Zhang ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Photothermal Therapy ◽  
Photoacoustic Imaging ◽  
Tungsten Bronze ◽  
Redox Status

Although various kinds of nanomaterials have been used as anticancer theranostics by exploiting the tumor microenvironment, relatively few nanomaterials can be efficiently activated by the tumor redox status for imaging and therapy.

NIR-controlled HSP90 inhibitor release from hollow mesoporous nanocarbon for synergistic tumor photothermal therapy guided by photoacoustic imaging

Nanoscale ◽  
2020 ◽  
Vol 12 (27) ◽  
pp. 14775-14787
Author(s):  
Jiaxin Sun ◽  
Yongjing Li ◽  
Yilong Teng ◽  
Sheng Wang ◽  
Jia Guo ◽  
...  
Keyword(s):  
Therapeutic Effect ◽  
Photothermal Therapy ◽  
Mesoporous Carbon ◽  
Photoacoustic Imaging ◽  
Drug Carriers ◽  
Hsp90 Inhibitor ◽  
Carbon Nanospheres ◽  
Mild Temperature

Hollow mesoporous carbon nanospheres were used as drug carriers for mild-temperature photothermal therapy, which showed a significant NIR-enhanced synergistic tumor therapeutic effect guided by photoacoustic imaging.

scholarly journals Research on Targeted Thermal Effect of Molybdenum Disulfide Nanosheets Modified by Nucleic Acid Aptamers

2020 ◽  
Vol 185 ◽  
pp. 04003
Author(s):  
Bo pang ◽  
Lihong Jin ◽  
Liying Wang
Keyword(s):  
Nucleic Acid ◽  
Molybdenum Disulfide ◽  
Therapeutic Effect ◽  
Photothermal Therapy ◽  
Effective Concentration ◽  
Tumor Treatment ◽  
Nucleic Acid Aptamers ◽  
Low Toxicity ◽  
Good Biocompatibility ◽  
Molybdenum Disulfide Nanosheets

In this paper, the surface of molybdenum disulfide nanosheets synthesized by hydrothermal method was modified with bovine serum albumin (BSA) and nucleic acid aptamers in order to construct a photothermal system with high target recognition, stable size, good biocompatibility and low toxicity Nano material molybdenum disulfide; Under 808 nm laser irradiation, suitable functionalized molybdenum disulfide nanosheets can produce singlet oxygen at an effective concentration for photodynamic therapy, and at the same time, photothermal therapy can also be used to achieve synergistic therapy and the therapeutic effect is more excellent. This shows that such functionalized molybdenum disulfide nanosheets have excellent therapeutic effect and great potential in tumor treatment.

Significance of systemic and local immune responses to the pathological therapeutic effect of neoadjuvant chemotherapy in breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12084-e12084
Author(s):  
Ryungsa Kim ◽  
Ami Kawai ◽  
Megumi Wakisaka ◽  
Yuri Funaoka ◽  
Sayaka Sawada ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Neoadjuvant Chemotherapy ◽  
Immune Responses ◽  
Nk Cells ◽  
Therapeutic Effect ◽  
Cell Activity ◽  
Multivariate Logistic Regression Analysis ◽  
Therapeutic Effects ◽  
Axillary Lymph

e12084 Background: Activation of the immune response including T lymphocytes, natural killer (NK) cells, and tumor microenvironment factors (TMEFs) is important in inducing a therapeutic response after neoadjuvant chemotherapy (NAC) in breast cancer. We examined the significance of systemic and local immune responses to the pathological therapeutic effect of NAC in breast cancer. Methods: From 2012 to 2018, 38 patients with stage II–III breast cancer received NAC with anthracyclines and taxanes followed by surgery. Therapeutic effects were evaluated according to the histopathology criteria for the assessment of therapeutic effects in breast cancer indicated by the Japanese Breast Cancer Society. Peripheral NK (pNK) cell activity was measured by chromium release assay. Levels of TMEFs were assessed by next-generation sequencing for CD4, CD8, NK, FOXP3, CTLA-4, PD-1, PD-L1, IL-2, IL-6, IL-12, IFN-γ, IL-10, TGF-β, and VEGF in FFPE sections collected from preoperative VAB samples and surgical specimens. Results: The stages, tumor subtypes, and therapeutic outcomes were as follows: II (N = 21), III (N = 17); luminal (N = 22), HER-2 positive (N = 12), TN (N = 4); G1a (N = 8), G1b (N = 13), G2a (N = 7), G2b (N = 4), G3 (i.e. complete) (N = 6). A G2 or better therapeutic effect were significantly associated with high post-NAC levels of NK, and potentially associated with higher CD4, CD8, and lower CTLA-4 after NAC. Multivariate logistic regression analysis showed that a G2 or better therapeutic effect was significantly associated with higher NK after NAC (OR = 1.07; 95% CI, 1.00–1.14; P = .0255). Disappearance of axillary lymph node metastasis was significantly associated with increased NK and pNK cell activity, as well as decreased VEGF level, and potentially associated with lower CTLA-4 after NAC. Conclusions: Increased NK cells after NAC are critical in producing a better therapeutic effect in collaboration with increased CD4 and CD8, and decreased CTLA-4 and VEGF. Systemic activation of pNK cells may improve the elimination of metastatic tumor cells in axillary lymph nodes by coordinating with release of immunosuppression derived from VEGF and activation of immune cells in the tumor microenvironment in breast cancer patients after NAC. An immune checkpoint inhibitor targeting CTLA-4 may improve NAC efficacy for breast cancer.

Flower-like Fe7S8/Bi2S3 superstructures with improved near-infrared absorption for efficient chemo-photothermal therapy

2019 ◽  
Vol 48 (10) ◽  
pp. 3360-3368 ◽  
Author(s):  
Qing Cao ◽  
Xin Guo ◽  
Wenlong Zhang ◽  
Guoqiang Guan ◽  
Xiaojuan Huang ◽  
...  
Keyword(s):  
Therapeutic Effect ◽  
Infrared Absorption ◽  
Photothermal Therapy ◽  
Near Infrared

Hydrophilic flower-like Fe7S8/Bi2S3 superstructures with improved near-infrared absorption and photostability for good chemo-photothermal synergistic therapeutic effect.

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