Infections and cancer: the "fifty shades of immunity" hypothesis (original) (raw)

Infection, immunoregulation, and cancer

As man has moved rapidly from the hunter-gatherer environment to the living conditions of the industrialized countries, the incidences of some cancers have increased alarmingly. Recent increases are usually attributed to dietary changes or to altered exposures to putative carcinogens associated with the modern lifestyle. However, the changes in cancer incidence parallel similar increases in non-neoplastic chronic inflammatory disorders (inflammatory bowel disease, allergies, and autoimmunity), and the epidemiology is often strikingly similar. This parallel is worth exploring, because the increases in chronic inflammatory disorders are at least partly explained by immunoregulatory defects resulting from diminished exposure to microorganisms that co-evolved with mammals and developed a role in driving immunoregulatory circuits (the hygiene hypothesis). Dysregulated chronic inflammation can drive oncogenesis and also provides growth and angiogenic factors that enhance the subsequent proliferation and spread of tumor cells. Thus, a modern failure to downregulate inappropriate inflammation could underlie increases in some cancers in parallel with the increases in chronic inflammatory disorders. This possibility is supported by recent work showing that in some circumstances regulatory T cells protect against cancer, rather than aggravating it, as previously assumed. A greater understanding of these interactions might pave the way to improved microbe-based immunotherapies.

Infection and Cancer: Revaluation of the Hygiene Hypothesis

Clinical Cancer Research, 2013

Several studies have shown that persistent infections and inflammation can favor carcinogenesis. At the same time, certain types of pathogens and antitumor immune responses can decrease the risk of tumorigenesis or lead to cancer regression. Infectious agents and their products can orchestrate a wide range of host immune responses, through which they may positively or negatively modulate cancer development and/or progression. The factors that direct this dichotomous influence of infection-mediated immunity on carcinogenesis are not well understood. Even though not universal, several previous reports have investigated the inverse link of pathogen-induced "benign" inflammation to carcinogenesis and various other pathologies, ranging from autoimmune diseases to allergy and cancer. Several models and ideas are discussed in this review, including the impact of decreased exposure to pathogens, as well as the influence of pathogen load, the timing of infection, and the type of instigated immune response on carcinogenesis. These phenomena should guide future investigations into identifying novel targets within the microbial and host proteome, which will assist in the development of cancer therapeutics and vaccine remedies, analogous to earlier efforts based on helminthic components for the prevention and/or treatment of several pathologies.

Pathogens and Cancer

Springer eBooks, 2022

Infectious agents play an aetiologic role in approximately 20% of cancer cases worldwide. At least, more than ten pathogens, including viruses, parasites, and bacteria are known to contribute to oncogenesis either directly via the expression of their protein products or indirectly via chronic inflammation (Table 1). To date, there are seven oncogenic viruses [human papillomavirus (HPV), Epstein-Barr virus (EBV), hepatitis virus B and C (HBV and HCV), human T-cell lymphoma virus 1 (HTLV-1), Merkel cell polyomavirus (MCPyV), and Kaposi's sarcoma virus (KSVH or HHV8)], one oncogenic bacterium (Helicobacter pylori), and three oncogenic parasites (Schistosoma haematobium, Opithorchis viverrini, and Clonorchis sinensis), identified as cancer-related pathogens. HBV, HCV, HPV, and H. pylori account for approximately 5% of all cancer cases by leading to hepatocellular carcinoma, cervical cancer and stomach cancer, respectively (Vandeven and Nghiem 2014). Pathogens can generally be divided into direct and indirect carcinogens (Figure 1). The direct carcinogenic pathogens HPV, HTLV-1, EBV, MCPyV and KSVH share several similarities. At least a critical portion of the viral genome can generally be detected in each cancer cell resulting in the expression of viral oncogenes that disrupt cell-cycle checkpoints, inhibit apoptosis and contribute to cell immortalisation. In contrast, the indirect carcinogenic pathogens (HBV, HCV, H. pylori, S. haematobium, O. viverrini, and C. sinensis) do not induce expression of oncogenes, but instead their persistent infection leads to a chronic inflammatory state or immunosuppression that limits the antitumour immune surveillance mechanisms. Because persistent infection is a hallmark of oncogenic pathogens, there is a window of opportunity for cancer prevention by treating the pathogen before malignant progression. Viral oncogenic mechanisms generally include: genomic instability, high rates of cell proliferation, resistance to apoptosis, abnormal DNA repair mechanisms, cell polarity changes and interference with telomere shortening, which often coexist with evasion of the antiviral immune response (Morales-Sánchez and Fuentes-Pananá 2014). Viral persistence and/or latency, in which there is no or little production of viral particles are biologically compatible with the carcinogenic process, due to avoiding of cell death while maintaining the infectious agent hidden from the immune system. Viral persistence in the host is achieved by integrating the viral genome into the cell genome or by expressing viral proteins that equally segregate the viral genome into daughter cells during cell partitioning. The net balance between virus and host preserve the integrity of both. Cell transformation is probably not an evolutionary viral strategy, but rather a biological accident that rarely occurs in the virus-host interaction. All virus-associated tumours result from the cooperation of various events, involving more than persistent infection and viral transformation mechanisms.

Infection as a causal factor of cancer

2012

By 2030 nearly one in five of all new cases of cancer in the world, and nearly one in six cancer deaths, will occur in Commonwealth member states (Ferley et al., 2010). Projections of the International Agency for Research on Cancer (IARC) indicate that the number of new cases of cancer in the Commonwealth will rise by more than 77 per cent – from 2,263,427 to 4,003,875 – and cancer deaths by more than 81 per cent – from 1,455,050 to 2,592,240 (ibid.). Lowand middle-income member states, particularly those in South Asia, will bear the brunt of this unfolding cancer pandemic where it is estimated that the number of new cancer cases will rise by 72 per cent and cancer deaths by more than 80 per cent (ibid.). Only effective prevention can reduce the incidence of cancer. A first step towards this is an understanding of the factors that predispose to cancer. These factors differ, often quite markedly, between the more and less developed countries and across different geographical regions....

Cancer and viruses: A double-edged sword

PROTEOMICS, 2012

Oncovirus, synonymously called a 'tumour virus', is a virus that can cause cancer. An oncolytic virus preferentially infects the host's cancer cells and lyses them, causing tumour destruction, and is thus referred to as a 'cancer killing virus'. With an estimated 11% of cancer-associated deaths caused by oncoviruses and the possibility that many cancers may be treated by using oncolytic viruses, the role of viruses in cancer may be viewed as a double-edged sword. A total of seven human cancer viruses have been identified as oncoviruses, having been associated with various cancers. Conversely, a large number of oncolytic viruses have shown great potential towards the treatment of certain types of cancer. Proteomics has now been applied towards understanding the complex interplay that exists between oncoviruses and the immune responses that serve to prevent oncoviral diseases. This review attempts to summarise the neoplastic potential of human tumour associated viruses and associated vaccine successes. The potential use of oncolytic viruses for the therapeutic intervention of cancer will also be discussed. Finally, this review will discuss the enormous potential of proteomics technology in the field of oncovirology.

Causal role of infectious agents in cancer: An overview

Caspian Journal of Internal Medicine, 2017

Cancer is a complex group of diseases with multiple eventual causes. The underlying causes are not fully known. Thus, learning more about the known causes of cancer is an important issue. Moreover, among these factors, infection and its association to cancers is controversial. Although, it seems that the genome instability of the cells can initiate cancer development. The purpose of this review was to present the role of infection in the development of cancer. Infectious agents, such as hepatitis B (HBV) and C viruses (HCV), Epstein-Barr virus (EBV), human papillomavirus (HPV), human immunodeficiency virus type 1 (HIV-1), Helicobacter pylori (H. pylori) and Streptococcus bovis (S. bovis) contribute to the pathogenesis of different cancers. These cancers include hepatocellular carcinoma, Burkitt's lymphoma, nasopharyngeal carcinoma, cervical cancers, non-Hodgkin lymphoma, Kaposi sarcoma, adenocarcinoma and lymphoma. Screenings of infectious diseases in cancer patients may open up areas of research in the identification of optimizing cancer control strategies.

Interplay between viruses and bacterial microbiota in cancer development

Seminars in Immunology, 2017

During the last few decades we have become accustomed to the idea that viruses can cause tumors. It is much less considered and discussed, however, that most people infected with oncoviruses will never develop cancer. Therefore, the genetic and environmental factors that tip the scales from clearance of viral infection to development of cancer are currently an area of active investigation. Microbiota has recently emerged as a potentially critical factor that would affect this balance by increasing or decreasing the ability of viral infection to promote carcinogenesis. In this review, we provide a model of microbiome contribution to the development of oncogenic viral infections and viral associated cancers, give examples of this process in human tumors, and describe the challenges that prevent progress in the field as well as their potential solutions.

Pathogens and Carcinogenesis: A Review

Biology

Cancer is a global health problem associated with genetics and unhealthy lifestyles. Increasingly, pathogenic infections have also been identified as contributors to human cancer initiation and progression. Most pathogens (bacteria, viruses, fungi, and parasites) associated with human cancers are categorized as Group I human carcinogens by the International Agency for Research on Cancer, IARC. These pathogens cause carcinogenesis via three known mechanisms: persistent infection that cause inflammation and DNA damage, initiation of oncogene expression, and immunosuppression activity of the host. In this review, we discuss the carcinogenesis mechanism of ten pathogens, their implications, and some future considerations for better management of the disease. The pathogens and cancers described are Helicobacter pylori (gastric cancer), Epstein-Barr virus (gastric cancer and lymphoma), Hepatitis B and C viruses (liver cancer), Aspergillus spp. (liver cancer), Opisthorchis viverrine (bile ...

Viral infections as a cause of cancer (Review)

International Journal of Oncology, 2007

In order to promote carcinogenesis multiple factors must be orchestrated. The alteration of the cellular genome after a carcinogenic exposure may result in malignancy if apoptosis is prevented and the immune surveillance fails to eliminate the transformed cell. Infectious agents may exert these properties and transform a host cell. Viruses associated with human cancer are known as 'tumor viruses'. Most of them are capable of integrating into the host genome and have the ability to immortalize the target cell in order to allow their own replication. The infected cell expresses the viral genes, which are able to induce cell growth, proliferation and prevent apoptosis. This review focuses on Epstein-Barr virus, human papilloma virus, hepatitis C virus, hepatitis B virus, human herpes virus 8 and human T-cell leukemia virus, since they have been already established as causative agents of human cancer. An understanding of the viral replication mechanism may provide new targets for the development of specified viral therapy that may have an impact not only on viral infections but in human cancer as well. Contents 1. Introduction 2. General aspects of viral oncogenesis 3. Human papilloma virus (HPV) 4. Hepatitis B virus (HBV) and hepatitis C virus (HCV) 5. Human herpes virus 8 (HHV-8) 6. Human T-cell leukemia virus type-1 (HTLV-1) 7. Conclusion