scholarly journals The Multifaceted Role of Macrophages in Oncolytic Virotherapy

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1570
Author(s):  
Laura Hofman ◽  
Sean E. Lawler ◽  
Martine L. M. Lamfers
Keyword(s):  
Immune System ◽  
Immune Evasion ◽  
Tumour Microenvironment ◽  
Oncolytic Viruses ◽  
Oncolytic Virotherapy ◽  
Comprehensive Overview ◽  
Central Function ◽  
Cancer Hallmarks ◽  
Viral Spread

One of the cancer hallmarks is immune evasion mediated by the tumour microenvironment (TME). Oncolytic virotherapy is a form of immunotherapy based on the application of oncolytic viruses (OVs) that selectively replicate in and induce the death of tumour cells. Virotherapy confers reciprocal interaction with the host’s immune system. The aim of this review is to explore the role of macrophage-mediated responses in oncolytic virotherapy efficacy. The approach was to study current scientific literature in this field in order to give a comprehensive overview of the interactions of OVs and macrophages and their effects on the TME. The innate immune system has a central influence on the TME; tumour-associated macrophages (TAMs) generally have immunosuppressive, tumour-supportive properties. In the context of oncolytic virotherapy, macrophages were initially thought to predominantly contribute to anti-viral responses, impeding viral spread. However, macrophages have now also been found to mediate transport of OV particles and, after TME infiltration, to be subjected to a phenotypic shift that renders them pro-inflammatory and tumour-suppressive. These TAMs can present tumour antigens leading to a systemic, durable, adaptive anti-tumour immune response. After phagocytosis, they can recirculate carrying tissue-derived proteins, which potentially enables the monitoring of OV replication in the TME. Their role in therapeutic efficacy is therefore multifaceted, but based on research applying relevant, immunocompetent tumour models, macrophages are considered to have a central function in anti-cancer activity. These novel insights hold important clinical implications. When optimised, oncolytic virotherapy, mediating multifactorial inhibition of cancer immune evasion, could contribute to improved patient survival.

Immunotherapy: New insights in breast cancer treatment

2021 ◽  
pp. 1-10
Author(s):  
Bader Alshehri
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Immune System ◽  
Cancer Treatment ◽  
Immune Evasion ◽  
Breast Tumor ◽  
Parp Inhibitor ◽  
Breast Cancer Treatment ◽  
New Treatment

Breast cancer being the most malignant and lethal disease persistent among women globally. Immunotherapy as a new treatment modality has emerged in understanding the loopholes in the treatment of breast cancer which is mainly attributed to the potential of tumor cells to evade and survive the immune response by developing various strategies. Therefore, improved understanding of the immune evasion by cancer cells and the monoclonal antibodies against PD- and PD-L1 can help us in the diagnosis of this malignancy. Here in this article, I have highlighted that in addition to focusing on other strategies for breast cancer treatment, the involvement of immune system in breast cancer is vital for the understanding of this malignancy. Further, the complete involvement of immune system in the relapse or recurrence of the breast tumor and have also highlighted the role of vaccines, PD-1 and CTLA-4 with the recent advances in the field. Moreover, in addition to the application of immunotherapy as a sole therapy, combinations of immunotherapy with various strategies like targeting it with MEK inhibitors, Vaccines, chemotherapy and PARP inhibitor has shown to have significant benefits is also discussed in this article.

scholarly journals Plasmodium evasion of mosquito immunity and global malaria transmission: The lock-and-key theory

2015 ◽  
Vol 112 (49) ◽  
pp. 15178-15183 ◽  
Author(s):  
Alvaro Molina-Cruz ◽  
Gaspar E. Canepa ◽  
Nitin Kamath ◽  
Noelle V. Pavlovic ◽  
Jianbing Mu ◽  
...  
Keyword(s):  
Immune System ◽  
Malaria Transmission ◽  
Immune Evasion ◽  
Mosquito Species ◽  
Haplotype Diversity ◽  
Malaria Vectors ◽  
Selective Force ◽  
Genetic Traits ◽  
Geographic Population

Plasmodium falciparum malaria originated in Africa and became global as humans migrated to other continents. During this journey, parasites encountered new mosquito species, some of them evolutionarily distant from African vectors. We have previously shown that the Pfs47 protein allows the parasite to evade the mosquito immune system of Anopheles gambiae mosquitoes. Here, we investigated the role of Pfs47-mediated immune evasion in the adaptation of P. falciparum to evolutionarily distant mosquito species. We found that P. falciparum isolates from Africa, Asia, or the Americas have low compatibility to malaria vectors from a different continent, an effect that is mediated by the mosquito immune system. We identified 42 different haplotypes of Pfs47 that have a strong geographic population structure and much lower haplotype diversity outside Africa. Replacement of the Pfs47 haplotypes in a P. falciparum isolate is sufficient to make it compatible to a different mosquito species. Those parasites that express a Pfs47 haplotype compatible with a given vector evade antiplasmodial immunity and survive. We propose that Pfs47-mediated immune evasion has been critical for the globalization of P. falciparum malaria as parasites adapted to new vector species. Our findings predict that this ongoing selective force by the mosquito immune system could influence the dispersal of Plasmodium genetic traits and point to Pfs47 as a potential target to block malaria transmission. A new model, the “lock-and-key theory” of P. falciparum globalization, is proposed, and its implications are discussed.

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 Zinc, Vitamin D and Vitamin C: Perspectives for COVID-19 With a Focus on Physical Tissue Barrier Integrity

2020 ◽  
Vol 7 ◽  
Author(s):  
José João Name ◽  
Ana Carolina Remondi Souza ◽  
Andrea Rodrigues Vasconcelos ◽  
Pietra Sacramento Prado ◽  
Carolina Parga Martins Pereira
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Viral Infections ◽  
Adequate Intake ◽  
High Demand ◽  
Comprehensive Overview ◽  
Disease Prognosis ◽  
Mucous Membranes ◽  
And Function

Some nutrients play key roles in maintaining the integrity and function of the immune system, presenting synergistic actions in steps determinant for the immune response. Among these elements, zinc and vitamins C and D stand out for having immunomodulatory functions and for playing roles in preserving physical tissue barriers. Considering the COVID-19 pandemic, nutrients that can optimize the immune system to prevent or lower the risk of severe progression and prognosis of this viral infection become relevant. Thus, the present review aims to provide a comprehensive overview of the roles of zinc and vitamins C and D in the immune response to viral infections, focusing on the synergistic action of these nutrients in the maintenance of physical tissue barriers, such as the skin and mucous membranes. The evidence found in the literature shows that deficiency of one or more of these three elements compromises the immune response, making an individual more vulnerable to viral infections and to a worse disease prognosis. Thus, during the COVID-19 pandemic, the adequate intake of zinc and vitamins C and D may represent a promising pharmacological tool due to the high demand for these nutrients in the case of contact with the virus and onset of the inflammatory process. Ongoing clinical trials will help to clarify the role of these nutrients for COVID-19 management.

scholarly journals Evolving Role of Oncolytic Virotherapy: Challenges and Prospects in Clinical Practice

2021 ◽  
pp. 432-441
Author(s):  
Omeed Moaven ◽  
Christopher W. Mangieri ◽  
John A. Stauffer ◽  
Panos Z. Anastasiadis ◽  
Mitesh J. Borad
Keyword(s):  
Clinical Practice ◽  
Treatment Options ◽  
Cytolytic Activity ◽  
Oncolytic Viruses ◽  
Treatment Modalities ◽  
Oncolytic Virotherapy ◽  
Novel Treatment ◽  
Genetically Engineer ◽  
Essential Components

Selective oncotropism and cytolytic activity against tumors have made certain viruses subject to investigation as novel treatment modalities. However, monotherapy with oncolytic viruses (OVs) has shown limited success and modest clinical benefit. The capacity to genetically engineer OVs makes them a desirable platform to design complementary treatment modalities to overcome the existing treatment options' shortcomings. In recent years, our knowledge of interactions of the tumors with the immune system has expanded profoundly. There is a growing body of literature supporting immunomodulatory roles for OVs. The concept of bioengineering these platforms to induce the desired immune response and complement the current immunotherapeutic modalities to make immune-resistant tumors responsive to immunotherapy is under investigation in preclinical and early clinical trials. This review provides an overview of attempts to optimize oncolytic virotherapy as essential components of the multimodality anticancer therapeutic approach and discusses the challenges in translation to clinical practice.

Dimethyl fumarate potentiates oncolytic virotherapy through NF-κB inhibition

2018 ◽  
Vol 10 (425) ◽  
pp. eaao1613 ◽  
Author(s):  
Mohammed Selman ◽  
Paula Ou ◽  
Christopher Rousso ◽  
Anabel Bergeron ◽  
Ramya Krishnan ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Human Tumor ◽  
Dimethyl Fumarate ◽  
Nuclear Factor Κb ◽  
Oncolytic Viruses ◽  
Oncolytic Virotherapy ◽  
Type I ◽  
Anticancer Properties ◽  
Viral Spread ◽  
Therapeutic Outcomes

Resistance to oncolytic virotherapy is frequently associated with failure of tumor cells to get infected by the virus. Dimethyl fumarate (DMF), a common treatment for psoriasis and multiple sclerosis, also has anticancer properties. We show that DMF and various fumaric and maleic acid esters (FMAEs) enhance viral infection of cancer cell lines as well as human tumor biopsies with several oncolytic viruses (OVs), improving therapeutic outcomes in resistant syngeneic and xenograft tumor models. This results in durable responses, even in models otherwise refractory to OV and drug monotherapies. The ability of DMF to enhance viral spread results from its ability to inhibit type I interferon (IFN) production and response, which is associated with its blockade of nuclear translocation of the transcription factor nuclear factor κB (NF-κB). This study demonstrates that unconventional application of U.S. Food and Drug Administration–approved drugs and biological agents can result in improved anticancer therapeutic outcomes.

scholarly journals Resistance Mechanisms Influencing Oncolytic Virotherapy, a Systematic Analysis

Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1166
Author(s):  
Darshak K. Bhatt ◽  
Roger Chammas ◽  
Toos Daemen
Keyword(s):  
Cancer Therapeutics ◽  
Therapy Resistance ◽  
Resistance Mechanisms ◽  
Oncolytic Viruses ◽  
Oncolytic Virotherapy ◽  
Original Research ◽  
Stromal Compartment ◽  
Systematic Analysis ◽  
Antiviral Responses ◽  
Viral Spread

Resistance to therapy is a frequently observed phenomenon in the treatment of cancer, and as with other cancer therapeutics, therapies based on oncolytic viruses also face the challenges of resistance, such as humoral and cellular antiviral responses, and tumor-associated interferon-mediated resistance. In order to identify additional mechanisms of resistance that may contribute to therapeutic failure, we developed a systematic search strategy for studies published in PubMed. We analyzed 6143 articles on oncolytic virotherapy and found that approximately 8% of these articles use resistance terms in the abstract and/or title. Of these 439 articles, 87 were original research. Most of the findings reported pertain to resistance mediated by tumor-cell-dependent interferon signaling. Yet, mechanisms such as epigenetic modifications, hypoxia-mediated inhibition, APOBEC-mediated resistance, virus entry barriers, and spatiotemporal restriction to viral spread, although not frequently assessed, were demonstrated to play a major role in resistance. Similarly, our results suggest that the stromal compartment consisting of, but not limited to, myeloid cells, fibroblasts, and epithelial cells requires more study in relation to therapy resistance using oncolytic viruses. Thus, our findings emphasize the need to assess the stromal compartment and to identify novel mechanisms that play an important role in conferring resistance to oncolytic virotherapy.

scholarly journals Current and emerging immunotherapeutic approaches to the treatment of multiple myeloma

2019 ◽  
Vol 10 ◽  
pp. 204062071985417
Author(s):  
Dawn Swan ◽  
Kevin Lynch ◽  
Mark Gurney ◽  
Michael O’Dwyer
Keyword(s):  
Multiple Myeloma ◽  
Immune System ◽  
Immune Evasion ◽  
Proteasome Inhibitors ◽  
Standard Of Care ◽  
Bispecific Antibodies ◽  
Clinical Use ◽  
Immunomodulatory Drugs ◽  
Care Regimes

Multiple myeloma (MM) has a worldwide incidence of 1–5/100,000/year. Outcomes have improved significantly in recent years following incorporation of immunomodulatory drugs and proteasome inhibitors into standard-of-care regimes. MM is profoundly immunosuppressive, enabling immune evasion, proliferation and disease progression. The role of the immune system in MM is becoming increasingly characterized and understood, and numerous therapies are under development or in routine clinical use targeting these elements of MM pathogenesis. In this review we discuss the immunosuppressive effects of MM, then the therapies targeting these defects. Specifically, we review the monoclonal and bispecific antibodies, alongside adoptive cellular therapies currently under investigation.

Role of the surface coat of Romanomermis culicivorax in immune evasion

Nematology ◽  
2007 ◽  
Vol 9 (1) ◽  
pp. 17-24 ◽  
Author(s):  
Edward Platzer ◽  
Randy Gaugler ◽  
Muhammad Shamseldean
Keyword(s):  
Immune System ◽  
Immune Evasion ◽  
Immune Reaction ◽  
Parasitic Nematodes ◽  
Broad Host Range ◽  
Host Immune System ◽  
Surface Coat ◽  
Mermithid Nematode ◽  
Host Parasite

AbstractInteractions of the mermithid nematode Romanomermis culicivorax with the immune system of mosquito larvae were examined by scanning electron microscopy. The host immune system rapidly recognised invading parasites, as granulocytes and discharged granules were observed attached to parasitic nematodes within 5 min. Melanin deposition was infrequently observed. As a counter measure, the parasites secreted and shed an extracellular surface coat which aided immune evasion. During the first 4 days of infection, when parasite growth was limited, the coat served as a disposable, renewable barrier between parasite and host that was intermittently shed to cleanse the nematode of adhering host immune products. In the later infection phase the parasite grew rapidly and was beyond the effect of the depleted host immune response. The broad host range of R. culcivorax within culicines may be partly a function of the nonspecific defence it mounts against the host immune system. In summary, shedding of the surface coat is an adaptive counter response by R. culicivorax to the mosquito immune reaction to infection and provides a classic example of host-parasite coevolution.

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