scholarly journals Immune modulatory effects of oncogenic KRAS in cancer

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Shaima’a Hamarsheh ◽  
Olaf Groß ◽  
Tilman Brummer ◽  
Robert Zeiser
Keyword(s):  
Clinical Trials ◽  
Immune System ◽  
Immune Modulation ◽  
Immune Escape ◽  
Human Cancer ◽  
Tumour Microenvironment ◽  
Main Driver ◽  
Frequent Mutations ◽  
Preclinical Work

Abstract Oncogenic KRAS mutations are the most frequent mutations in human cancer, but most difficult to target. While sustained proliferation caused by oncogenic KRAS-downstream signalling is a main driver of carcinogenesis, there is increasing evidence that it also mediates autocrine effects and crosstalk with the tumour microenvironment (TME). Here, we discuss recent reports connecting KRAS mutations with tumour-promoting inflammation and immune modulation caused by KRAS that leads to immune escape in the TME. We discuss the preclinical work on KRAS-induced inflammation and immune modulation in the context of currently ongoing clinical trials targeting cancer entities that carry KRAS mutations and strategies to overcome the oncogene-induced effects on the immune system.

New Trends in Anti-Cancer Therapy: Combining Conventional Chemotherapeutics with Novel Immunomodulators

2018 ◽  
Vol 25 (36) ◽  
pp. 4758-4784 ◽  
Author(s):  
Amy L. Wilson ◽  
Magdalena Plebanski ◽  
Andrew N. Stephens
Keyword(s):  
Clinical Trials ◽  
Cell Death ◽  
Immune System ◽  
Cancer Therapy ◽  
Immune Cell ◽  
Cytotoxic T Lymphocyte ◽  
Tumour Microenvironment ◽  
Immune Checkpoints ◽  
Tumour Regression ◽  
Cell Trafficking

Cancer is one of the leading causes of death worldwide, and current research has focused on the discovery of novel approaches to effectively treat this disease. Recently, a considerable number of clinical trials have demonstrated the success of immunomodulatory therapies for the treatment of cancer. Monoclonal antibodies can target components of the immune system to either i) agonise co-stimulatory molecules, such as CD137, OX40 and CD40; or ii) inhibit immune checkpoints, such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death-1 (PD-1) and its corresponding ligand PD-L1. Although tumour regression is the outcome for some patients following immunotherapy, many patients still do not respond. Furthermore, chemotherapy has been the standard of care for most cancers, but the immunomodulatory capacity of these drugs has only recently been uncovered. The ability of chemotherapy to modulate the immune system through a variety of mechanisms, including immunogenic cell death (ICD), increased antigen presentation and depletion of regulatory immune cells, highlights the potential for synergism between conventional chemotherapy and novel immunotherapy. In addition, recent pre-clinical trials indicate dipeptidyl peptidase (DPP) enzyme inhibition, an enzyme that can regulate immune cell trafficking to the tumour microenvironment, as a novel cancer therapy. The present review focuses on the current immunological approaches for the treatment of cancer, and summarizes clinical trials in the field of immunotherapy as a single treatment and in combination with chemotherapy.

scholarly journals INDOLEAMINE 2,3 DIOXYGENASE AS AN IMMUNOTHERAPEUTIC TARGET BRINGS A NEW HOPE FOR CANCER PATIENTS

2018 ◽  
Vol 4 (3) ◽  
Author(s):  
Kashif Asghar ◽  
Asif Loya
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Cancer Colorectal ◽  
Immune Escape ◽  
Mammalian Target Of Rapamycin ◽  
Tumour Microenvironment ◽  
Indoleamine 2,3 Dioxygenase ◽  
Wide Range ◽  
Ido Inhibitors

Therapeutic manipulation of immune system in cancer has been an extensive area of research in the field of oncoimmunology. Immunotherapy helps the immune system to combat against cancer. Tumour cells take an edge of immunosuppressive mechanisms and inhibit antitumour immune responses. Indoleamine 2,3 dioxygenase (IDO) is an immunosuppressive enzyme which is involved in tumour immune escape mechanism in various cancers. IDO can degrade the tryptophan into kynurenines and has an ability to enhance the immune tolerance through mammalian target of rapamycin pathway general control nonderepressible 2 (GCN2) pathway and induction of regulatory T (T-regs) cells. IDO-induced T-regs suppress the local immune responses in the tumour microenvironment and promote metastasis. IDO overexpression in various cancers is associated with poor prognosis. Several preclinical and clinical trials have been proceeding and recommend that IDO inhibitor may be an influential tool against a wide range of cancers. IDO inhibitors as adjuvant therapeutic agents may also have clinical implications. Thus, IDO has the potential to be used as an immunotherapeutic target. This review discusses the promising role of IDO in cancer and its implication in immunotherapy.Key words: Breast cancer, colorectal cancer, haematological malignancies, immunotherapy, indoleamine 2,3-dioxygenase, pancreatic cancer, prostate cancer

scholarly journals Next Generation of Advanced Non-Small Cell Lung Cancer Therapy: Targeted and Immuno-Therapies

2020 ◽  
Vol 8 (1) ◽  
pp. 26-32
Author(s):  
Sze Wah Samuel Chan ◽  
Elliot Smith
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Immune System ◽  
Small Molecule ◽  
Growth Factor Receptor ◽  
Tumour Microenvironment ◽  
Next Generation ◽  
Growth And Survival ◽  
Improve Patient Survival ◽  
Lung Cancer Therapy

Lung cancer is one of the deadliest cancers in the world. Current clinical trials are focused on developing the next generation of therapies that target novel anti-cancer mechanisms. One approach is to prime the immune system, as the cancer has been known to suppress immune cells in the tumour microenvironment. Using pharmacotherapy, the immune system can be unleashed and suppress the cancer’s growth. Another pathway is targeting known oncogenic genes that are important for the cancer’s growth and survival. In lung cancer, the epidermal growth factor receptor and several other mutated proteins are targets of small-molecule inhibitors that have been shown to drastically improve patient survival and quality of life. Discussed in this review are broad highlights of the different immunotherapies and small molecule targeted therapies that have been studied in the latest clinical trials for lung cancer.

The Immune System Regulation in Sepsis: From Innate to Adaptive

2019 ◽  
Vol 20 (8) ◽  
pp. 799-816 ◽  
Author(s):  
Yue Qiu ◽  
Guo-wei Tu ◽  
Min-jie Ju ◽  
Cheng Yang ◽  
Zhe Luo
Keyword(s):  
Clinical Trials ◽  
Immune System ◽  
Systemic Inflammatory Response Syndrome ◽  
Inflammatory Response ◽  
Immune Cells ◽  
Current Knowledge ◽  
Systemic Inflammatory Response ◽  
Immune System Regulation

Sepsis, which is a highly heterogeneous syndrome, can result in death as a consequence of a systemic inflammatory response syndrome. The activation and regulation of the immune system play a key role in the initiation, development and prognosis of sepsis. Due to the different periods of sepsis when the objects investigated were incorporated, clinical trials often exhibit negative or even contrary results. Thus, in this review we aim to sort out the current knowledge in how immune cells play a role during sepsis.

ACE2/Angiotensin-(1-7)/Mas Receptor Axis in Human Cancer: Potential Role for Pediatric Tumors

2020 ◽  
Vol 21 (9) ◽  
pp. 892-901 ◽  
Author(s):  
Ana Luiza Ataide Carneiro de Paula Gonzaga ◽  
Vitória Andrade Palmeira ◽  
Thomas Felipe Silva Ribeiro ◽  
Larissa Braga Costa ◽  
Karla Emília de Sá Rodrigues ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Angiotensin Ii ◽  
Pediatric Cancer ◽  
Pediatric Patients ◽  
Human Cancer ◽  
Experimental Studies ◽  
At1 Receptor ◽  
Pediatric Tumors ◽  
Mas Receptor

Background: Pediatric tumors remain the highest cause of death in developed countries. Research on novel therapeutic strategies with lesser side effects is of utmost importance. In this scenario, the role of Renin-Angiotensin System (RAS) axes, the classical one formed by angiotensinconverting enzyme (ACE), Angiotensin II and AT1 receptor and the alternative axis composed by ACE2, Angiotensin-(1-7) and Mas receptor, have been investigated in cancer. Objective: This review aimed to summarize the pathophysiological role of RAS in cancer, evidence for anti-tumor effects of ACE2/Angiotensin-(1-7)/Mas receptor axis and future therapeutic perspectives for pediatric cancer. Methods: Pubmed, Scopus and Scielo were searched in regard to RAS molecules in human cancer and pediatric patients. The search terms were “RAS”, “ACE”, “Angiotensin-(1-7)”, “ACE2”, “Angiotensin II”, “AT1 receptor”, “Mas receptor”, “Pediatric”, “Cancer”. Results: Experimental studies have shown that Angiotensin-(1-7) inhibits the growth of tumor cells and reduces local inflammation and angiogenesis in several types of cancer. Clinical trials with Angiotensin-( 1-7) or TXA127, a pharmaceutical grade formulation of the naturally occurring peptide, have reported promising findings, but not enough to recommend medical use in human cancer. In regard to pediatric cancer, only three articles that marginally investigated RAS components were found and none of them evaluated molecules of the alternative RAS axis. Conclusion: Despite the potential applicability of Angiotensin-(1-7) in pediatric tumors, the role of this molecule was never tested. Further clinical trials are necessary, also including pediatric patients, to confirm safety and efficiency and to define therapeutic targets.

scholarly journals 1-Methylnicotinamide is an immune regulatory metabolite in human ovarian cancer

2021 ◽  
Vol 7 (4) ◽  
pp. eabe1174
Author(s):  
Marisa K. Kilgour ◽  
Sarah MacPherson ◽  
Lauren G. Zacharias ◽  
Abigail E. Ellis ◽  
Ryan D. Sheldon ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Modulation ◽  
Human Cancer ◽  
Serous Carcinoma ◽  
Necrosis Factor Alpha ◽  
Methyl Group ◽  
Cytokine Tumor Necrosis Factor ◽  
Factor Alpha ◽  
Immunotherapy Target ◽  
Necrosis Factor

Immune regulatory metabolites are key features of the tumor microenvironment (TME), yet with a few exceptions, their identities remain largely unknown. Here, we profiled tumor and T cells from tumor and ascites of patients with high-grade serous carcinoma (HGSC) to uncover the metabolomes of these distinct TME compartments. Cells within the ascites and tumor had pervasive metabolite differences, with a notable enrichment in 1-methylnicotinamide (MNA) in T cells infiltrating the tumor compared with ascites. Despite the elevated levels of MNA in T cells, the expression of nicotinamide N-methyltransferase, the enzyme that catalyzes the transfer of a methyl group from S-adenosylmethionine to nicotinamide, was restricted to fibroblasts and tumor cells. Functionally, MNA induces T cells to secrete the tumor-promoting cytokine tumor necrosis factor alpha. Thus, TME-derived MNA contributes to the immune modulation of T cells and represents a potential immunotherapy target to treat human cancer.

scholarly journals Medicinal Plants and Mushrooms with Immunomodulatory and Anticancer Properties—A Review on Hong Kong’s Experience

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2173
Author(s):  
Grace Gar-Lee Yue ◽  
Clara Bik-San Lau ◽  
Ping-Chung Leung
Keyword(s):  
Clinical Trials ◽  
Medicinal Plants ◽  
Infection Control ◽  
Immune Modulation ◽  
Evidence Based ◽  
Medicinal Mushroom ◽  
Immunomodulatory Effects ◽  
Anticancer Properties ◽  
Further Development ◽  
Insight Into

The immune modulating effects of selected herbs deserve careful studies to gain evidence-based support for their further development. We have been working hard on many items of medicinal herbs to gain insight into their immunomodulatory effects relevant to cancer treatment in particular, while infection control is not excluded. Nine of them have been selected to give the results of our exploration on their biological, particularly immunomodulatory activities. Since Hong Kong people especially favor one medicinal mushroom, viz. Coriolus versicolor, a number of clinical trials using Coriolus for cancer-related studies are included in this review. While immune modulation platforms are being built for relevant studies, a brief account on the research targets and related procedures are given.

scholarly journals Oncolytic Virotherapy Treatment of Breast Cancer: Barriers and Recent Advances

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1128
Author(s):  
Amy Kwan ◽  
Natalie Winder ◽  
Munitta Muthana
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Cell Death ◽  
Immune System ◽  
Menopausal Status ◽  
Oncolytic Virotherapy ◽  
Immunogenic Cell Death ◽  
Tumour Type ◽  
Common Cancer ◽  
Direct Cell

Oncolytic virotherapy (OV) is an emerging class of immunotherapeutic drugs. Their mechanism of action is two-fold: direct cell lysis and unmasking of the cancer through immunogenic cell death, which allows the immune system to recognize and eradicate tumours. Breast cancer is the most common cancer in women and is challenging to treat with immunotherapy modalities because it is classically an immunogenically “cold” tumour type. This provides an attractive niche for OV, given viruses have been shown to turn “cold” tumours “hot,” thereby opening a plethora of treatment opportunities. There has been a number of pre-clinical attempts to explore the use of OV in breast cancer; however, these have not led to any meaningful clinical trials. This review considers both the potential and the barriers to OV in breast cancer, namely, the limitations of monotherapy and the scope for combination therapy, improving viral delivery and challenges specific to the breast cancer population (e.g., tumour subtype, menopausal status, age).

scholarly journals Recent Findings on Cell-Based Therapies for COVID19-Related Pulmonary Fibrosis

2021 ◽  
Vol 30 ◽  
pp. 096368972199621
Author(s):  
Hong-Meng Chuang ◽  
Li-Ing Ho ◽  
Horng-Jyh Harn ◽  
Ching-Ann Liu
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Pulmonary Fibrosis ◽  
Tissue Repair ◽  
Immune Modulation ◽  
Distress Syndrome ◽  
Clinical Symptoms ◽  
The United States ◽  
Past Experiences ◽  
Respiratory Tract Inflammation

COVID-19 has spread worldwide, including the United States, United Kingdom, and Italy, along with its site of origin in China, since 2020. The virus was first found in the Wuhan seafood market at the end of 2019, with a controversial source. The clinical symptoms of COVID-19 include fever, cough, and respiratory tract inflammation, with some severe patients developing an acute and chronic lung injury, such as acute respiratory distress syndrome (ARDS) and pulmonary fibrosis (PF). It has already claimed approximately 300 thousand human lives and the number is still on the rise; the only way to prevent the infection is to be safe till vaccines and reliable treatments develop. In previous studies, the use of mesenchymal stem cells (MSCs) in clinical trials had been proven to be effective in immune modulation and tissue repair promotion; however, their efficacy in treating COVID-19 remains underestimated. Here, we report the findings from past experiences of SARS and MSCs, and how SARS could also induce PF. Such studies may help to understand the rationale for the recent cell-based therapies for COVID-19.

scholarly journals Mesenchymal stem cells and oncolytic viruses: joining forces against cancer

2021 ◽  
Vol 9 (2) ◽  
pp. e001684
Author(s):  
Rafael Moreno
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Immune System ◽  
Oncolytic Viruses ◽  
Immunogenic Cell Death ◽  
The Past ◽  
Physical Barriers ◽  
Immunogenic Properties ◽  
New Strategies

The development of oncolytic viruses (OVs) has increased significantly in the past 20 years, with many candidates entering clinical trials and three of them receiving approval for some indications. Recently, OVs have also gathered interest as candidates to use in combination with immunotherapies for cancer due to their immunogenic properties, which include immunogenic cell death and the possibility to carry therapeutic transgenes in their genomes. OVs transform non-immunogenic ‘cold’ tumors into inflamed immunogenic ‘hot’ tumors, where immunotherapies show the highest efficacy. However, in monotherapy or in combination with immunotherapy, OVs face numerous challenges that limit their successful application, in particular upon systemic administration, such as liver sequestration, neutralizing interactions in blood, physical barriers to infection, and fast clearance by the immune system. In this regard, the use of mesenchymal stem cells (MSCs) as cells carrier for OV delivery addresses many of these obstacles acting as virus carriers and factories, expressing additional transgenes, and modulating the immune system. Here, I review the current progress of OVs-loaded MSCs in cancer, focusing on their interaction with the immune system, and discuss new strategies to improve their therapeutic efficacy.

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