Noncoding RNAs as potential mediators of resistance to cancer immunotherapy

Publication date: Available online 14 November 2019Source: Seminars in Cancer BiologyAuthor(s): Radhakrishnan Vishnubalaji, Shaath Hibah, Ramesh Elango, Nehad M. AlajezAbstractSubstantial evolution in cancer therapy has been witnessed lately, steering mainly towards immunotherapeutic approaches, replacing or in combination with classical therapies. Whereas the use of various immunotherapy approaches, such as adoptive T cell therapy, genetically-modified T cells, or immune checkpoint inhibitors, has been a triumph for cancer immunotherapy, the great challenge is the ability of the immune system to sustain long lasting anti-tumor response. Additionally, epigenetic changes in a suppressive tumor microenvironment can pertain to T cell exhaustion, limiting their functionality. Noncoding RNAs (ncRNAs) have emerged over the last years as key players in epigenetic regulation. Among those, microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) have been studied extensively for their potential role in regulating tumor immunity through direct regulation of genes involved in immune activation or suppression. In this review, we will provide an overview of contemporary approaches for cancer immunotherapy and will present the current state of knowledge implicating miRNAs and lncRNAs in regulating immune response against human cancer and their potential implications in resistance to cancer immunotherapy, with main emphasis on immune checkpoints.
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research

Related Links:

(Yale University) In the last decade, scientists discovered that blocking a key regulator of the immune system helped unleash the body's natural defenses against several forms of cancer, opening up a new era of cancer immunotherapy. Now Yale scientists have essentially flipped this script and found that when impaired a molecularly similar regulator can cause the damaging immune system attacks on skin and organs that are the hallmark of the autoimmune disease lupus.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
AbstractCurrent therapeutic approaches in malignancy are often based on combination therapies, reflecting present understanding of the way different players act together in cancer. The cooperative activity of several elements can potentiate the pro-metastatic functions of the cancer cells and of the tumor microenvironment (TME), together leading to a more aggressive disease phenotype. The design of improved therapeutic modalities requires better identification of networks that act at specific cancer-related settings, and of the molecular mechanisms involved. Such studies will indicate if therapies that co-target several fa...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
PPARγ Agonists in Combination Cancer Therapies. Curr Cancer Drug Targets. 2019 Dec 08;: Authors: Mrowka P, Glodkowska-Mrowka E Abstract Peroxisome proliferator-activated receptor-gamma (PPARγ) is a nuclear receptor acting as a transcription factor involved in the regulation of energy metabolism, cell cycle, cell differentiation, and apoptosis. These unique properties constitute a strong therapeutic potential that place PPARγ agonists as one of the most interesting and widely studied anticancer molecules. Although PPARγ agonists exert significant, antiproliferative and tumoricid...
Source: Current Cancer Drug Targets - Category: Cancer & Oncology Authors: Tags: Curr Cancer Drug Targets Source Type: research
In this study, we generated two types of EGFR-specific CAR-modified T cells using lentiviral vectors with DNA sequences encoding the scFv regions of two anti-EGFR antibodies. The cytotoxic and antitumor effects of these CAR-modified T cells were examined in cytokine release and cytotoxicity assays in vitro and in tumor growth assays in TNBC cell line- and patient-derived xenograft mouse models. Both types of EGFR-specific CAR-T cells were activated by high-EGFR-expressing TNBC cells and specifically triggered TNBC cell lysis in vitro. Additionally, the CAR-T cells inhibited growth of cell-line- and patient-derived xenograf...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research
AbstractPro-inflammatory cytokines are crucial mediators of cancer development, representing potential targets for cancer therapy. The molecular mechanism of a vital pro-inflammatory cytokine, IL-17A, in cancer progression and its potential use in therapy through influencing fatty acid (FA) metabolism, especially FA uptake of cancer cells, remains unknown. In the present study, we used IL-17A and ovarian cancer (OvCa), a representative of both obesity-related and inflammation-related cancers, to explore the interactions among IL-17A, cancer cells and adipocytes (which can provide FAs). We found that in the presence of palm...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
Researchers from Case Western Reserve University have developed a new computational tool to predict, based on CT imaging, whether lung cancer patients will benefit from immune-checkpoint inhibitor cancer therapy. This is an exciting development for p...
Source: Medgadget - Category: Medical Devices Authors: Tags: Informatics Medicine Source Type: blogs
Abstract Nanoparticles in cancer therapy have garnered significant attention in the past few decades. Cancer immunotherapy, which is aptly called "the new-generation cancer therapy," is slowly making remarkable strides in the improvement of patient outcome and longevity. Taken together, nanoparticles in immune therapy have the potential to offer advantages of both nanoparticles and immune therapy on a single platform. PMID: 31776928 [PubMed - in process]
Source: Mol Biol Cell - Category: Molecular Biology Authors: Tags: Methods Mol Biol Source Type: research
The approval of two chimeric antigen receptor-modified T cell types by the US Food and Drug Administration (FDA) for the treatment of hematologic malignancies is a milestone in immunotherapy; however, the appl...
Source: Journal of Hematology and Oncology - Category: Hematology Authors: Tags: Review Source Type: research
AbstractA major challenge of cancer immunotherapy is the potential for undesirable effects on bystander cells and tumor-associated immune cells. Fundamentally, we need to understand what effect targeting tumor metabolism has upon the metabolism and phenotype of tumor-associated leukocytes, whose function can be critical for effective cancer therapeutic strategies. Undesirable effects of cancer therapeutics are a major reason for drug-associated toxicity, which confounds drug dosing and efficacy. As with any chemotherapeutic agent, drugs targeting tumor metabolism will exert potent effects on host stromal cells and tumor-as...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
ConclusionOur results demonstrate that p53 activation mediated by APG-115 promotes antitumor immunity in the tumor microenvironment (TME) regardless of theTrp53 status of tumors per se. Instead, such an effect depends on p53 activation inTrp53 wild-type immune cells in the TME. Based on the data, a phase 1b clinical trial has been launched for the evaluation of APG-115 in combination with pembrolizumab in solid tumor patients including those withTP53mut tumors.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
More News: Biology | Cancer | Cancer & Oncology | Cancer Therapy | Genetics | Immunotherapy