Infections and cancer: the “fifty shades of immunity” hypothesis

Abstract

BackgroundSince the beginning of the twentieth century, infection has emerged as a fundamental aspect of cancer causation with a growing number of pathogens recognized as oncogenic. Meanwhile, oncolytic viruses have also attracted considerable interest as possible agents of tumor destruction.DiscussionLost in the dichotomy between oncogenic and oncolytic agents, the indirect influence of infectious organisms on carcinogenesis has been largely unexplored. We describe the various ways – from functional aspects to evolutionary considerations such as modernity mismatches – by which infectious organisms could interfere with oncogenic processes through immunity. Finally, we discuss how acknowledging these interactions might impact public health approaches and suggest new guidelines for therapeutic and preventive strategies both at individual and population levels.SummaryInfectious organisms, that are not oncogenic neither oncolytic, may play a significant role in carcinogenesis, suggesting the need to increase our knowledge about immune interactions between infections and cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3234-4) contains supplementary material, which is available to authorized users.

Childhood infectious diseases and risk of non‐Hodgkin's lymphoma according to the WHO classification: A reanalysis of the Italian multicenter case–control study

“…Protection against adult malignancies by common childhood infection agents might result from a large set of both direct and indirect mechanisms. For instance, an oncotropic and oncolytic effect has been demonstrated for some viruses, including the mumps and measles agents; multiple common infections may hamper the proliferation of potentially oncogenic viruses by induction of the release of IFN; some antibiotic treatments against childhood bacterial infections may exert a toxic activity against cancer stem cells; exposure to childhood infections may enhance immune efficiency to eliminate cancer cells by favoring a balanced TH1/TH2 immunity; antibodies against childhood viruses may favor the destruction of cancer and precursor cancer cells via partial cross‐immunity . With regard to NHL, an oncogenic effect by a still unknown common infectious agent (perhaps a replication‐defective polyomavirus) has also been proposed .…”

“…For instance, an oncotropic and oncolytic effect has been demonstrated for some viruses, including the mumps and measles agents; multiple common infections may hamper the proliferation of potentially oncogenic viruses by induction of the release of IFN; some antibiotic treatments against childhood bacterial infections may exert a toxic activity against cancer stem cells; exposure to childhood infections may enhance immune efficiency to eliminate cancer cells by favoring a balanced TH1/TH2 immunity; antibodies against childhood viruses may favor the destruction of cancer and precursor cancer cells via partial cross-immunity. 25,26 With regard to NHL, an oncogenic effect by a still unknown common infectious agent (perhaps a replicationdefective polyomavirus) has also been proposed. 25 According to this hypothesis, subjects exposed to multiple infections during childhood are more likely to have had a contact also with this agent and, as a consequence, to have developed antibodies against both the wild-type and the mutated potentially oncogenic virus.…”

Ancient oncogenesis, infection and human evolution

“…In addition to >110 environmental substances known to be highly carcinogenic to humans, the International Agency for Research on Cancer (http://www.iarc.fr/) classifies ~370 chemical compounds and microorganisms as “probably carcinogenic” to humans. Although the influence of infectious organisms on carcinogenesis requires considerable exploration (Jacqueline et al., ), ~45 species of bacteria (including H. pylori , Chlamydia trachomatis , Salmonella typhi and Streptococcus bovis ), viruses (e.g., hepatitis B, C and D virus, Epstein–Barr virus, Kaposi's sarcoma herpesvirus and HPV) and parasitic microorganisms (e.g., P. falciparum , Opisthorchis viverrini and Schistosoma haematobium ) are currently listed as recognized causal factors in oncogenesis. Several oncogenic viruses (Epstein–Barr virus, HPV, human T‐lymphotropic virus type 1 and KSHV) are responsible for pathogen‐specific cancers (Table ).…”

“…In fact, when pooled, these figures amount to a startling 44.2% probability that viral, bacterial and parasitic pathogens are implicated directly in oncogenesis in sub‐Saharan Africa (Figure ). And as infectious organisms not currently regarded as oncogenic may play a significant role in carcinogenesis (Jacqueline et al., ), it must be envisaged that the incidence of cancer in prehistory is also greatly underestimated.…”

Infection triggers tumor regression through activation of innate immunity inDrosophila

“…As numerous immune mechanisms are shared by anti-infection and anti-cancer responses (3), it is theoretically expected that the personal history of infections could influence cancer cell elimination/proliferation in the body. For instance, evidences are accumulating to suggest that infectious agents may play an indirect role in tumor progression, through immunological, ecological and evolutionary interactions with immune system (4). Moreover, early work from William Coley as well as many other reports have unambiguously linked infection to tumor regression in cancer patients (5,6) suggesting that non-specific immunity may be particularly relevant for cancer treatment (7).…”