Targeting Immune-Related Molecules in Cancer Therapy: A Comprehensive In Vitro Analysis on Patient-Derived Tumor Models.

This study investigated the impact of immune-related pathway inhibition, among them indolamine 2,3-dioxygenase (IDO), alone and together with immune cells on growth and viability of colorectal cancer (CRC) cells. A panel of patient-derived CRC cell lines with different molecular characteristics (CpG island methylator phenotype, chromosomal, and microsatellite instability) was included. Initial phenotyping of CRC cell lines (n=17) revealed high abundance of immunosuppressive checkpoint-molecules in general, but an individual profile for IDO. Presence of immune-related molecules was independent of the molecular subtype. Selective treatment of CRC cell lines showing high or low IDO expression (n=2 cell lines each) was performed with single agents and combinations of Indoximod, Curcumin, and Gemcitabine with and without the addition of peripheral blood lymphocytes (PBL) in an allogeneic setting. All substances affected CRC cell growth in a cell line specific manner. The combination of Curcumin and Gemcitabine proved to be most effective in tumor cell elimination. Functional read-out analyses identified cellular senescence, after both single and combined treatment. Curcumin alone exerted strong cytotoxic effects by inducing early and late apoptosis. Necrosis was not detectable at all. Addition of lymphocytes generally boosted antitumoral effects of all IDO-inhibitors, with up to 80 % cytotoxicity for the Curcumin treatment. Here, no obvious differences became apparent between indi...
Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int Source Type: research

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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
Conclusions In the new era of targeted therapy, treatment options are increasingly based on the precise molecular and genetic profiling of tumor cells (58). Currently, the main challenge for further novel drug development in targeted therapy is the clarification of specific molecular mechanisms underlying the varied forms of tumors in clinic. It has been acknowledged that cancer is caused by a set of driver mutations. In this regard, it is of great significance to: (1) identify and validate key mutant genes and proteins in cancers as new targets; (2) identify patients most likely and unlikely to benefit from certain targe...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
This study was supported by the Shanghai Sailing Program [grant number 17YF1425200, 2017]; Chinese National Natural Science Funding [grant number 81702249, 2017]; Science and Technology Commission of Shanghai Municipality [grant number 17511103403, 2017]; The funder has no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Acknowledgments We acknowledge the ex...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Discussion Suppressor of cytokine signaling 1 is an essential molecule for maintaining immune homeostasis and subverting inflammation. Disorders arising from excess inflammation or SOCS1 deficiency can be potentially treated with SOCS1 mimetics (Ahmed et al., 2015). While SOCS1 has promising potential in many disorders, it should be noted that new targets and actions of SOCS1 are still being discovered and not all the effects of this protein are beneficial in autoimmune diseases and cancer. For instance, SOCS1 degrades IRS1 and IRS2, required for insulin signaling, via the SOCS Box domain, thus, limiting its potential in ...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Personalized Dendritic Cell Vaccines—Recent Breakthroughs and Encouraging Clinical Results Beatris Mastelic-Gavillet, Klara Balint, Caroline Boudousquie, Philippe O. Gannon and Lana E. Kandalaft* Department of Oncology, Center for Experimental Therapeutics, Ludwig Center for Cancer Research, University of Lausanne, Lausanne, Switzerland With the advent of combined immunotherapies, personalized dendritic cell (DC)-based vaccination could integrate the current standard of care for the treatment of a large variety of tumors. Due to their proficiency at antigen presentation, DC are key coordinators of the innate...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions The current review reports recent epidemiological and experimental data supporting the bright future of dietary polyphenols as chemopreventive, anti-inflammatory, immunomodulatory, and anticancer agents in CRC (Figure 1). The polyphenol-rich diet not only may represent a chemopreventive treatment but also has important function on immune system by promoting symbiont and commensal bacterial populations, increases reciprocal interaction between host and microbiota which in turn have important effects on immune function Evidence underlines the use of polyphenols as sensitizers of chemo/radiotherapies paving the w...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Hepatoma-Derived Growth Factor and DDX5 Promote Carcinogenesis and Progression of Endometrial Cancer by Activating β-Catenin Chunhua Liu1†, Lijing Wang1†, Qingping Jiang2†, Junyi Zhang3†, Litong Zhu1, Li Lin1, Huiping Jiang1, Dan Lin1, Yanyi Xiao1, Weiyi Fang1,3 and Suiqun Guo1* 1Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China 2Department of Pathology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China 3Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guang...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusion In this article, we use the amphiphilic copolymer DSPE-SS-mPEG, which is connected by disulfide bonds. Afterward, the magnetic Fe3O4 nanoparticles and the hydrophobic drug are made by the self-assembly of the amphiphilic copolymer. DOX is encapsulated in the amphiphilic copolymer to form a magnetic nano drug controlled release system which is sensitive and responds to a reducing environment. This controlled release system can dissociate the disulfide bonds in the presence of dithiothreitol, thereby triggering the release system to disintegrate and expel the drug. When the DOX-loaded nanocarrier is transported ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, this study demonstrates that WG-391D exhibits strong antitumor activity against ovarian cancer and indicates that the down-regulation of CDC25B by inhibitors could provide a rationale for ovarian cancer therapy. Introduction Ovarian cancer is one of the most common malignances in females. The American Cancer Society estimated that there were 22,240 cases of ovarian cancer, and 14,070 deaths, in the United States in 2018 (1). During its early stages, ovarian cancer can be asymptomatic; hence, ~70% of patients have advanced disease when diagnosed and ultimately develop chemotherapeutic drug resistance an...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Abstract: Genomic analyses in oncologic care allow for the development of more precise clinical laboratory tests that will be critical for personalized pharmacotherapy. Traditional biopsy-based approaches are limited by the availability of sequential tissue specimens to detect resistance. Blood-based genomic profiling (“liquid biopsy”) is useful for longitudinal monitoring of tumor genomes and can complement biopsies. Tumor-associated mutations can be identified in cell-free tumor DNA (ctDNA) from patient blood samples and used for monitoring disease activity. The US Food and Drug Administration approved a li...
Source: Therapeutic Drug Monitoring - Category: Drugs & Pharmacology Tags: Review Articles: Focus on Pharmacodynamic Drug Monitoring Source Type: research
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