Abstract
This review explores the incessant evolutionary interaction and co-development between immune system evolution and somatic evolution, to put it into context with the short, over 60-year, detailed human study of this extraordinary protective system. Over millions of years, the evolutionary development of the immune system in most species has been continuously shaped by environmental interactions between microbes, and aberrant somatic cells, including malignant cells. Not only has evolution occurred in somatic cells to adapt to environmental pressures for survival purposes, but the immune system and its function has been successively shaped by those same evolving somatic cells and microorganisms through continuous adaptive symbiotic processes of progressive simultaneous immunological and somatic change to provide what we observe today. Indeed, the immune system as an environmental influence has also shaped somatic and microbial evolution. Although the immune system is tuned to primarily controlling microbiological challenges for combatting infection, it can also remove damaged and aberrant cells, including cancer cells to induce long-term cures. Our knowledge of how this occurs is just emerging. Here we consider the connections between immunity, infection and cancer, by searching back in time hundreds of millions of years to when multi-cellular organisms first began. We are gradually appreciating that the immune system has evolved into a truly brilliant and efficient protective mechanism, the importance of which we are just beginning to now comprehend. Understanding these aspects will likely lead to more effective cancer and other therapies.
Highlights
This review explores the incessant evolutionary interaction and codevelopment between immune system evolution and somatic evolution, to put it into context with the short, over 60-year, detailed human study of this extraordinary protective system
Aberration is detected by a variety of innate non-specific immune mechanisms through damage-associated molecular patterns (DAMPs) that are released in response to trauma or injury to tissues, such as heat-shock proteins (HSPs) when cancer cells are injured; and pathogen associated molecular patterns (PAMPs) which are a variety of molecules associated with pathogens usually recognized by the innate immune system through toll-like receptors (TLRs) which include bacterial lipopolysaccharides, glycoconjugates, viral proteins and endotoxins
Concluding Remarks and Implications knowledge has deeply developed concerning the immune system and cancer immunology, our contemporary understanding needs to be placed in evolutionary perspective
Summary
Any reports and responses or comments on the article can be found at the end of the article. To oppose mutated, infected and otherwise aberrant cells, the immune system has a number of adaptive and protective mechanisms These include somatic hypermutation genes for generation of hypervariable region binding domains for antibody molecules produced by plasma (B-) cells, and for the process of genetic recombination by T-cells forming the variable regions of T-cell surface receptors for rapid response to antigen exposure. It is clear that the immune system is not ignorant to the presence of tumours, that it does recognise tumour antigens, and that the normal homeostatic regulatory mechanisms suppress active anti-tumour immune responses, and are at the seat of the problem This explains why immuno-modulatory agents, such as IL2, and CTLA4, PD1/L1 monoclonal antibodies can deliver random dramatic complete responses in a limited percentage of late-stage cancer patients by releasing the pre-existing homeostatic suppression/tolerance[1,125,126,127,128,129,130]. Author information CSO Biotempus Ltd, the institutional affiliation for MA, has gone into liquidation since version 1 of this article was published
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