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2.
Int Rev Immunol ; 38(6): 267-283, 2019.
Article in English | MEDLINE | ID: mdl-31578892

ABSTRACT

Failure of treatment strategies against cancers is a major issue engaging many scientists to investigate the possible resistance factors. Cancer stem cells (CSCs) subvert promising therapeutic methods by developing resistant cancers. These pluripotent cells are located in individual microenvironments called cancer niche. CSCs affect the immune cells and on the flip side, the immune cells in the cancer niche influence them. Thereby, the interaction between CSCs and immune cells in cancer niche needs to be clearly studied in order to develop novel efficient methods of immune-based cancer treatment. In this article, we review literature about the suggested methods of CSC escape from immune responses and the effect of cancer niche characteristics on the ability of CSCs to develop resistant strains of cancers. Moreover, we discuss immune-mediated tumor targeting methods and bring in trials focused on CSC targeted therapies. We aim to help physicians to reach a consensus about using CSC-targeted immunotherapy methods and emerge novel immunotherapy methods through disrupting the interaction between immune cells and CSCs in the tumor microenvironment.


Subject(s)
Neoplasms/etiology , Neoplasms/metabolism , Neoplastic Stem Cells/metabolism , Animals , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/immunology , Cell Transformation, Neoplastic/metabolism , Cytokines/metabolism , Disease Models, Animal , Disease Susceptibility , Epithelial-Mesenchymal Transition/genetics , Epithelial-Mesenchymal Transition/immunology , Humans , Immune System/drug effects , Immune System/immunology , Immune System/metabolism , Immunotherapy , Inflammation Mediators/metabolism , Molecular Targeted Therapy , Neoplasms/pathology , Neoplasms/therapy , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/immunology , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Tumor Escape , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunology
3.
Mod Pathol ; 32(1): 70-80, 2019 01.
Article in English | MEDLINE | ID: mdl-30154578

ABSTRACT

The level of tumor-infiltrating lymphocytes and presence of tertiary lymphoid structures are significant prognostic and predictive factors in primary breast cancer. However, the understanding about differences in tumor-infiltrating lymphocytes and tertiary lymphoid structures at various metastatic sites or between primary breast tumors and metastatic sites is limited. A total of 335 cases of metastatic breast cancer from four metastatic sites (lung, liver, brain, and ovary) were included. We analyzed the percentages of tumor-infiltrating lymphocytes and presence of tertiary lymphoid structures in the primary and metastatic sites. The mean level of tumor-infiltrating lymphocytes in the lung metastases was higher than in the liver, brain, ovary, and matched primary tumors, while metastatic tumors of the liver and brain showed lower levels of tumor-infiltrating lymphocytes than primary tumors. Tertiary lymphoid structures were only found in the lung and liver, and in cases of brain metastases the change of tertiary lymphoid structures from present to absent significantly affected the level of tumor-infiltrating lymphocytes in metastases compared with that in matched primary tumors. Patients with a lower histological grade, hormone receptor positivity in primary tumors and metastases, a lower level of tumor-infiltrating lymphocytes and absence of tertiary lymphoid structures in primary tumors, a higher level of tumor-infiltrating lymphocytes and presence of tertiary lymphoid structures in metastases, and lung metastases showed significantly better overall survival. Our results showed that metastatic breast tumors in the lung had more tumor-infiltrating lymphocytes than did tumors at other sites and matched primary tumors. In addition, the presence of tertiary lymphoid structures in metastatic sites is a critical factor for the level of tumor-infiltrating lymphocytes.


Subject(s)
Breast Neoplasms/pathology , Breast Neoplasms/secondary , Lymphocytes, Tumor-Infiltrating/pathology , Neoplasm Metastasis/pathology , Tertiary Lymphoid Structures/pathology , Adult , Aged , Breast Neoplasms/immunology , Female , Humans , Lymphocytes, Tumor-Infiltrating/immunology , Middle Aged , Neoplasm Metastasis/immunology , Tertiary Lymphoid Structures/immunology
4.
Artif Cells Nanomed Biotechnol ; 45(4): 808-816, 2017 Jun.
Article in English | MEDLINE | ID: mdl-27263545

ABSTRACT

To concentrate a potent anticancer drug (Arteether) in tumor microenvironment, we encapsulated it in biodegradable and pH sensitive polyurethane (PU) nanomicelles (NMs). The nanocomplex was characterized by Fourier transform infrared (FTIR), dynamic light scattering (DLS). The loading capacity and release profile in pH of 5.4 and 7.4 were considered. The cytotoxicity effect was evaluated in vitro and in vivo settings. The level of IFN-γ and IL-4 cytokines of mice splenocytes were assessed by enzyme-linked immunosorbent assay (ELISA). The nanocomplex showed negative zeta charge of -26.2 mV, size of 42.30 nm and high loading capacity (92%). Release profile showed a faster rate of drug liberation at pH 5.4 as compared to that of pH 7.4. It indicated significant inhibitory effect on the growth of 4T1 cell line and increased IFN-γ level.


Subject(s)
Artemisinins/chemistry , Artemisinins/pharmacology , Breast Neoplasms/immunology , Drug Carriers/chemistry , Mammary Neoplasms, Experimental/immunology , Micelles , Nanoparticles/chemistry , Polyurethanes/chemistry , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Artemisinins/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Cell Line, Tumor , Cytokines/metabolism , Drug Liberation , Female , Hydrogen-Ion Concentration , Hydrophobic and Hydrophilic Interactions , Mammary Neoplasms, Experimental/drug therapy , Mice , Mice, Inbred BALB C , Solubility , Tumor Burden/drug effects , Tumor Burden/immunology , Water/chemistry
5.
Biointerphases ; 10(2): 029510, 2015 Jun 23.
Article in English | MEDLINE | ID: mdl-25908593

ABSTRACT

In this paper, a new configuration of a cold atmospheric pressure plasma jet has been designed and constructed. Poly-methyl-methacrylate was used as a new dielectric in this configuration which in comparison to other dielectrics is inexpensive, more resistant against break, and also more shapeable. Then, the plasma jet parameters such as plume temperature, rotational and vibrational temperatures, power, electrical behavior (voltage and current profile), electron density, and the produced reactive species were characterized. In order to determine the jet temperature and the amount of reactive species, effects of applied voltage, gas flow rate, and distance from the nozzle were studied. The power of the jet was specified using Lissajous curve approach. The plume temperature of the plasma jet was about the room temperature. Optical emission spectroscopy determined the type of reactive species, and also electron density and its corresponding plasma frequency (~6.4 × 10(13) cm(-3) and 4.52 × 10(11) Hz). Because of producing different reactive species, the device can be used in different applications, especially in plasma medicine. Thus, 4T1 cancer cells were treated using this plasma jet. The results showed that this plasma jet has a great potential to kill one of the most aggressive and resistant cancerous cell lines.


Subject(s)
Antineoplastic Agents/metabolism , Atmospheric Pressure , Cell Survival/drug effects , Epithelial Cells/drug effects , Epithelial Cells/physiology , Free Radicals/metabolism , Plasma Gases , Animals , Cell Line, Tumor , Mice
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