scholarly journals GSH depletion liposome adjuvant for augmenting the photothermal immunotherapy of breast cancer

2020 ◽  
Vol 6 (36) ◽  
pp. eabc4373 ◽  
Author(s):  
Zhanwei Zhou ◽  
Hui Wu ◽  
Ruoxi Yang ◽  
Alan Xu ◽  
Qingyan Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Tumor Cells ◽  
Abscopal Effect ◽  
Oxygen Species ◽  
Oxidation Treatment ◽  
Tumor Tissues ◽  
Redox Level ◽  
Antigen Presenting ◽  
Dc Maturation

The high redox level of tumor microenvironment inhibits the oxidation treatment and the immune response. Here, we innovatively develop maleimide liposome (ML) adjuvants to promote immunogenic cell death (ICD) induction and dendritic cells (DCs) maturation by glutathione (GSH) depletion for augmenting the photothermal immunotherapy of breast cancer. The ML effectively depletes the intracellular GSH and up-regulates reactive oxygen species (ROS) in both tumor cells and DCs. In tumor cells, the ROS boosted the ABTS·+ production to activate photothermal-induced ICD. In DCs, it relieved the immunosuppression, promoting DC maturation (57%) and antigen presenting. As a result of the ML assistant, the therapeutic systems improved the infiltration of CD8+ T cells to 53% in tumor tissues, eliciting strong abscopal effect and antimetastasis effect. The MLs were believed to be a superior candidate of adjuvants for enhancing immune response and cancer therapeutic efficacy.

scholarly journals The Abscopal Effect: Could a Phenomenon Described Decades Ago Become Key to Enhancing the Response to Immune Therapies in Breast Cancer?

Breast Care ◽  
2020 ◽  
Vol 15 (5) ◽  
pp. 443-449
Author(s):  
Hans-Christian Kolberg ◽  
Oliver Hoffmann ◽  
René Baumann
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Checkpoint Inhibitors ◽  
Immune Therapy ◽  
Antitumor Immune Response ◽  
Abscopal Effect ◽  
Antitumor Effects ◽  
Effective Combination ◽  
Immunological Mechanisms ◽  
Immune Therapies

Background: The term “abscopal effect” was defined in 1953. In oncology the term is used to describe systemic antitumor effects triggered by local irradiation (nontarget effect). Although the mechanism of the abscopal effect is not completely understood yet, it has been demonstrated that in situ tumor vaccination, and the resulting antitumor immune response, is one of the key factors. Summary: The development of immune therapies has recently led to concepts combining local radiotherapy and immune therapy with the aim of enhancing the response to immune therapy by the immunological mechanisms summarized in the term abscopal effect. This concept has also been investigated in less immunogenic tumors such as breast cancer. Initial data are promising but the hypothesis that the combination of checkpoint inhibitors and local radiotherapy could be an effective combination in breast cancer has to be proven by ongoing trials. Substitution of local radiotherapy by local hyperthermia could be an option in selected cases. Key Messages: Combination of checkpoint inhibitors with local radiation or hyperthermia in breast cancer is a promising approach and could enhance the response rates generated by immune therapy alone through the antitumor immune response initiated by the abscopal effect.

scholarly journals Breast Tumor Cells Highly Resistant to Drugs Are Controlled Only by the Immune Response Induced in an Immunocompetent Mouse Model

2019 ◽  
Vol 18 ◽  
pp. 153473541984804 ◽  
Author(s):  
Paola Lasso ◽  
Mónica Llano Murcia ◽  
Tito Alejandro Sandoval ◽  
Claudia Urueña ◽  
Alfonso Barreto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Tumor Cells ◽  
High Capacity ◽  
Cancer Cell Line ◽  
Tumor Model ◽  
Main Element ◽  
In Vivo Models

Background: The tumor cells responsible for metastasis are highly resistant to chemotherapy and have characteristics of stem cells, with a high capacity for self-regeneration and the use of detoxifying mechanisms that participate in drug resistance. In vivo models of highly resistant cells allow us to evaluate the real impact of the immune response in the control of cancer. Materials and Methods: A tumor population derived from the 4T1 breast cancer cell line that was stable in vitro and highly aggressive in vivo was obtained, characterized, and determined to exhibit cancer stem cell (CSC) phenotypes (CD44+, CD24+, ALDH+, Oct4+, Nanog+, Sox2+, and high self-renewal capacity). Orthotopic transplantation of these cells allowed us to evaluate their in vivo susceptibility to chemo and immune responses induced after vaccination. Results: The immune response induced after vaccination with tumor cells treated with doxorubicin decreased the formation of tumors and macrometastasis in this model, which allowed us to confirm the immune response relevance in the control of highly chemotherapy-resistant ALDH+ CSCs in an aggressive tumor model in immunocompetent animals. Conclusions: The antitumor immune response was the main element capable of controlling tumor progression as well as metastasis in a highly chemotherapy-resistant aggressive breast cancer model.

scholarly journals Activity of Antioxidant Enzymes in the Tumor and Adjacent Noncancerous Tissues of Non-Small-Cell Lung Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Marzena Zalewska-Ziob ◽  
Brygida Adamek ◽  
Janusz Kasperczyk ◽  
Ewa Romuk ◽  
Edyta Hudziec ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Tumor Cells ◽  
Oxygen Species ◽  
Glutathione S Transferase ◽  
Experimental Systems ◽  
Sod Isoforms ◽  
High Oxygen Pressure ◽  
Tumor Tissues ◽  
Mnsod Activity

Lung tissue is directly exposed to high oxygen pressure, as well as increased endogenous and exogenous oxidative stress. Reactive oxygen species (ROS) generated in these conditions play an important role in the initiation and promotion of neoplastic growth. In response to oxidative stress, the antioxidant activity increases and minimizes ROS-induced injury in experimental systems. The aim of the present study was to evaluate the activity of antioxidant enzymes, such as superoxide dismutase (SOD; isoforms: Cu/ZnSOD and MnSOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST), along with the concentration of malondialdehyde (MDA) in tumor and adjacent noncancerous tissues of two histological types of NSCLC, i.e., adenocarcinoma and squamous cell carcinoma, collected from 53 individuals with surgically resectable NSCLC. MDA concentration was similar in tumors compared with adjacent noncancerous tissues. Tumor cells had low MnSOD activity, usually low Cu/ZnSOD activity, and almost always low catalase activity compared with those of the corresponding tumor-free lung tissues. Activities of GSH-related enzymes were significantly higher in tumor tissues, irrespective of the histological type of cancer. This pattern of antioxidant enzymes activity could possibly be the way by which tumor cells protect themselves against increased oxidative stress.

Demasking of epithelial cell adhesion molecule (EpCAM) on circulating epithelial tumor cells by Tween®20 treatment in breast cancer patients

2012 ◽  
Vol 50 (4) ◽  
Author(s):  
Katya Hekimian ◽  
Ernst-Ludwig Stein ◽  
Ulrich Pachmann ◽  
Katharina Pachmann
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Cell Adhesion ◽  
Epithelial Cell ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cell Adhesion Molecule ◽  
Breast Cancer Patients ◽  
Epithelial Cell Adhesion Molecule ◽  
Epithelial Tumor

AbstractThe epithelial cell adhesion molecule (EpCAM) embedded in the plasma membrane of circulating epithelial tumor cells (CETC) is used for detection and enrichment of circulating tumor cells in peripheral blood and as a target for anti-epithelial antibodies elicited during immune response in anti-tumor immunization. Although an efficient immune response against EpCAM can be generated, the clinical application of such approaches has not been successful so far and the detection of circulating epithelial cells is highly variable. One reason for these discrepancies may be that not all circulating tumor cells are equally accessible for the specific antibody. A possible reason might be masking of EpCAM by glycoproteins or membrane lipoproteins preventing antibody binding.We have tested the application of detergents as demasking agents known to be successful in demasking red blood cell epitopes and determined how and in which way they affect integral membrane proteins and membrane lipids.The results showed that the polysorbate TweenThe data presented in this study suggest that EpCAM is present on part of circulating tumor cells in a masked form and that it is possible to demask EpCAM on CETC of breast cancer patients using Tween

scholarly journals Dendritic Cells in Sepsis: Pathological Alterations and Therapeutic Implications

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Dong-Dong Wu ◽  
Tao Li ◽  
Xin-Ying Ji
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Wnt Signaling Pathway ◽  
Reactive Oxygen Species Generation ◽  
Oxygen Species ◽  
Toll Like Receptor ◽  
Innate And Adaptive Immunity ◽  
Therapeutic Implications ◽  
Surface Molecules ◽  
Antigen Presenting

Sepsis is the leading cause of death for critically ill patients in recent years. Dendritic cells (DCs) are important antigen-presenting cells and play a key role in immune response by regulating the innate and adaptive immunity. The number of DCs, the differentiation of monocytes into DCs, and the levels of surface molecules associated with the function of DCs are changed in the development of sepsis. There are many mechanisms involved in the alterations of DCs during sepsis, including the induction of apoptosis, reactive oxygen species generation, activation of the Wnt signaling pathway, epigenetic regulation, and variation in Toll-like receptor-dependent signaling. In this review, we present the classifications of DC subsets and mechanisms involved in the alterations of DCs in sepsis, as well as further discuss the therapeutic strategies targeting DCs in sepsis to improve the aberrant immune response and prolong the life during sepsis progression.

scholarly journals Cancer cell CCR2 orchestrates suppression of the adaptive immune response

2020 ◽  
Vol 217 (10) ◽  
Author(s):  
Miriam R. Fein ◽  
Xue-Yan He ◽  
Ana S. Almeida ◽  
Emilis Bružas ◽  
Arnaud Pommier ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Adaptive Immune Response ◽  
Adaptive Immune ◽  
Genetic Targeting ◽  
Dc Maturation

C-C chemokine receptor type 2 (CCR2) is expressed on monocytes and facilitates their recruitment to tumors. Though breast cancer cells also express CCR2, its functions in these cells are unclear. We found that Ccr2 deletion in cancer cells led to reduced tumor growth and approximately twofold longer survival in an orthotopic, isograft breast cancer mouse model. Deletion of Ccr2 in cancer cells resulted in multiple alterations associated with better immune control: increased infiltration and activation of cytotoxic T lymphocytes (CTLs) and CD103+ cross-presenting dendritic cells (DCs), as well as up-regulation of MHC class I and down-regulation of checkpoint regulator PD-L1 on the cancer cells. Pharmacological or genetic targeting of CCR2 increased cancer cell sensitivity to CTLs and enabled the cancer cells to induce DC maturation toward the CD103+ subtype. Consistently, Ccr2−/− cancer cells did not induce immune suppression in Batf3−/− mice lacking CD103+ DCs. Our results establish that CCR2 signaling in cancer cells can orchestrate suppression of the immune response.

scholarly journals microRNAs in the Antitumor Immune Response and in Bone Metastasis of Breast Cancer: From Biological Mechanisms to Therapeutics

2020 ◽  
Vol 21 (8) ◽  
pp. 2805 ◽  
Author(s):  
Marta Gomarasca ◽  
Paola Maroni ◽  
Giuseppe Banfi ◽  
Giovanni Lombardi
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Formation Process ◽  
Immune Escape ◽  
Antitumor Immune Response ◽  
Metastasis Formation ◽  
Biological Mechanisms ◽  
Aberrant Expression

Breast cancer is the most common type of cancer in women, and the occurrence of metastasis drastically worsens the prognosis and reduces overall survival. Understanding the biological mechanisms that regulate the transformation of malignant cells, the consequent metastatic transformation, and the immune surveillance in the tumor progression would contribute to the development of more effective and targeted treatments. In this context, microRNAs (miRNAs) have proven to be key regulators of the tumor-immune cells crosstalk for the hijack of the immunosurveillance to promote tumor cells immune escape and cancer progression, as well as modulators of the metastasis formation process, ranging from the preparation of the metastatic site to the transformation into the migrating phenotype of tumor cells. In particular, their deregulated expression has been linked to the aberrant expression of oncogenes and tumor suppressor genes to promote tumorigenesis. This review aims at summarizing the role and functions of miRNAs involved in antitumor immune response and in the metastasis formation process in breast cancer. Additionally, miRNAs are promising targets for gene therapy as their modulation has the potential to support or inhibit specific mechanisms to negatively affect tumorigenesis. With this perspective, the most recent strategies developed for miRNA-based therapeutics are illustrated.

scholarly journals Subverting Subversion: A Review on the Breast Cancer Microenvironment and Therapeutic Opportunities

2015 ◽  
Vol 9s2 ◽  
pp. BCBCR.S29423 ◽  
Author(s):  
Ethan Rothschild ◽  
Debabrata Banerjee
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Adaptive Immune Response ◽  
Suppressor Cells ◽  
Cancer Cell Growth ◽  
Chemotherapy Drugs ◽  
Tumor Growth And Metastasis ◽  
Novel Target

This review combines the recent research on the subject of tumor immunology and methods of correcting the immune system's reaction to the tumor microenvironment while impeding the survival and growth of tumor cells, with a focus on breast cancer. Induction of hypoxia-inducible genes in the microenvironment leads to lowering of its pH. This impedes the adaptive immune response and acts to recruit cells of the immune system, which suppress the immune response. Regulatory T-cells (Tregs), myeloid-derived suppressor cells (MDSCs), and their derivatives coordinate an anti-autoimmunity response and a healing response in concert with tumor-secreted cytokines, enzymes, and antigens. Together, they suppress a proper immune reaction to tumor cells and promote cellular reproduction ( Fig. 1 ). In addition, the hypoxia-inducible response and components of the tumor microenvironment such as cancer-associated fibroblasts (CAFs) also create an ideal environment for tumor growth and metastasis via neoangiogenesis and increased motility. Broad-spectrum chemotherapy drugs are problematic as breast cancer cells develop resistance through selective loss of a novel target and downregulation of apoptotic factors. A better understanding of the tumor microenvironment offers new therapeutic opportunities to rescue the immune response, inhibit cancer cell growth pathways, and subvert the tumor microenvironment with little toxicity and side effects.

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