Adoptive transfer of osteoclast-expanded natural killer cells for immunotherapy targeting cancer stem-like cells in humanized mice

Abstract Based on data obtained from oral, pancreatic and lung cancers, glioblastoma, and melanoma, we have established that natural killer (NK) cells target cancer stem-like cells (CSCs). CSCs displaying low MHC class I, CD54, and PD-L1 are killed by cytotoxic NK cells and are differentiated by split anergized NK cells through both membrane bound and secreted forms of TNF-α and IFN-γ. NK cells select and differentiate both healthy and transformed stem-like cells, resulting in target cell maturation and shaping of their microenvironment. In our recent studies, we have observed that oral, pancreatic, and melanoma CSCs were capable of forming large tumors in humanized bone marrow, liver, thymus (hu-BLT) mice with fully reconstituted human immune system. In addition, major human immune subsets including NK cells, T cells, B cells, and monocytes were present in the spleen, bone marrow, peripheral blood, and tumor microenvironment. Similar to our previously published in vitro data, CSCs differentiated with split anergized NK cells prior to implantation in mice formed smaller tumors. Intravenous injection of functionally potent osteoclast-expanded NK cells inhibited tumor growth through differentiation of CSCs in humanized mice. In this review, we present current approaches, advances, and existing limitations in studying interactions of the immune system with the tumor, in particular NK cells with CSCs, using in vivo preclinical hu-BLT mouse model. In addi...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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CONCLUSIONS: Based on safety and tolerability, mivebresib RP2D is 1.5mg for the daily schedule, 2.5mg for 4/7 and 3mg for M-W-F. Mivebresib has a tolerable safety profile and stable disease was observed in some patients with malignant solid tumors. PMID: 31420359 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Gulcin Tezcan1, Ekaterina V. Martynova1, Zarema E. Gilazieva1, Alan McIntyre2, Albert A. Rizvanov1 and Svetlana F. Khaiboullina1,3* 1Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia 2Centre for Cancer Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, United Kingdom 3Department of Microbiology and Immunology, University of Nevada, Reno, Reno, NV, United States Inflammation has a crucial role in protection against various pathogens. The inflammasome is an intracellular multiprotein signaling complex that is linked to pathogen sensing and...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
This study aimed to investigate whether combining anti-PD-L1 Atezolizumab with BEV may have a synergistic effect and enhance the efficacy of both treatments in cisplatin resistant epithelial ovarian cancer (CREOC). We retrospectively analyzed 124 epithelial ovarian cancer (EOC) patients from Gynecologic Oncology Department of Tianjin Cancer Hospital between January 2013 and June 2018, who all were diagnosed with cisplatin resistance due to progressing
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In this study, we identified 37 genus-level core bacteria from feces of 101 healthy mice with different ages, sexes, and mouse strains in three previous studies. They collectively represented nearly half of the total sequences, and predominantly included carbohydrate- and amino acids-metabolizing bacteria and immunomodulatory bacteria. Among them, Anaerostipes indwelt the gut of all healthy mice. Co-abundance analysis showed that these core genera were clustered into five groups (Group C1–C5), which were ecologically related. For example, the abundances of Group C2 including probiotics Bifidobacterium and Lactobacill...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Ginevra Doglioni1,2†, Sweta Parik1,2† and Sarah-Maria Fendt1,2* 1Laboratory of Cellular Metabolism and Metabolic Regulation, VIB-KU Leuven Center for Cancer Biology, VIB, Leuven, Belgium 2Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute, Leuven, Belgium Metastasis formation is the leading cause of death in cancer patients. Thus, understanding and targeting this process is an unmet need. Crucial steps during the establishment of metastases include the (pre)metastatic niche formation. This process relies on the interaction of th...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusion Although treatment with BRAF inhibitors provides rapid response in most patients, treatment resistance persists. The few clinical studies of BRAF inhibitor resistance in patients indicate that genetic alterations that activate MAPK/Erk make up half of resistance mechanisms. Preclinical studies of BRAF inhibitor resistance in melanoma support the mechanisms observed in patients and indicate that the development of resistance is more complex than single mutations. In vitro models may be very helpful in studying mechanisms in the other half of patients with no known genetic driver of BRAF inhibitor resistance. Ove...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Chan Feng1, Donglei Zhu1, Lv Chen1, Yonglin Lu1, Jie Liu1, Na Yoon Kim2, Shujing Liang1, Xia Zhang1, Yun Lin1, Yabin Ma3* and Chunyan Dong1* 1Cancer Center, Shanghai East Hospital, Tongji University, Shanghai, China 2Department of Chemical Engineering, Northeastern University, Boston, MA, United States 3Pharmacy Department, Shanghai East Hospital, Tongji University, Shanghai, China The off-target activation of photosensitizers is one of the most well-known obstacles to effective photodynamic therapy (PDT). The selected activation of photosensitizers in cancer cells is highly desired to overcome this problem. We...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
In this study, T cells deficient in TRAF6 display enhanced T cell activation, CD28-indpendent stimulation and resistance to Treg cell-mediated suppression (176). Although TLR signaling can promote T cell resistance to Treg cells, the precise molecular mechanism remains yet to be elucidated. It is worth noting that TLR stimulation of T cells increases cytokine production (173, 177), thus future studies should delineate the effect of TLR-MyD88 signaling vs. subsequently induced cytokines in generating resistance to Treg cells. Lastly, it is also crucial to evaluate the effect of TLR signaling on regulatory T cells which also...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsIn this review, we summarize the mechanisms by which curcumin may affect EMT in cells under pathological conditions to understand its potential as a novel anti-tumor agent. Curcumin can exert chemo-preventive effects by inhibition and reversal of the EMT process through both TGF- β-dependent (e.g. in hepatoma and retinal pigment epithelial cancer) and -independent (e.g. in oral cancer, colorectal cancer, pancreatic cancer, hepatocellular carcinoma, breast cancer, melanoma, prostate cancer, bladder cancer, thyroid cancer and lung cancer) pathways. Curcumin can also mitigate chemoresistance through EMT suppre...
Source: Cellular Oncology - Category: Cancer & Oncology Source Type: research
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