Evolving strategies for cancer and autoimmunity: back to the future.

Peter J L Lane,David R Withers,Maher G Nawaf,Fabrina M Gaspal,Graham Anderson,Fiona M Mcconnell

doi:10.3389/fimmu.2014.00154

Peter J L Lane, David R Withers + Show 4 more

Open Access

https://doi.org/10.3389/fimmu.2014.00154

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Abstract

Although current thinking has focused on genetic variation between individuals and environmental influences as underpinning susceptibility to both autoimmunity and cancer, an alternative view is that human susceptibility to these diseases is a consequence of the way the immune system evolved. It is important to remember that the immunological genes that we inherit and the systems that they control were shaped by the drive for reproductive success rather than for individual survival. It is our view that human susceptibility to autoimmunity and cancer is the evolutionarily acceptable side effect of the immune adaptations that evolved in early placental mammals to accommodate a fundamental change in reproductive strategy. Studies of immune function in mammals show that high affinity antibodies and CD4 memory, along with its regulation, co-evolved with placentation. By dissection of the immunologically active genes and proteins that evolved to regulate this step change in the mammalian immune system, clues have emerged that may reveal ways of de-tuning both effector and regulatory arms of the immune system to abrogate autoimmune responses whilst preserving protection against infection. Paradoxically, it appears that such a detuned and deregulated immune system is much better equipped to mount anti-tumor immune responses against cancers.

Highlights

In our society today, cancer and autoimmunity are major causes of suffering and death, and a huge financial burden on health services worldwide
If one accepts Zinkernagel’s view that the development of memory and high affinity antibodies is a strategy optimized for reproductive success rather than individual survival, the Foxp3KOOX40CD30KO immune system in our view represents the “minimal immune system for health,” the necessary and sufficient platform that had evolved in the common mammalian ancestor before the evolution of high affinity antibodies and memory induced a compromise in the form of susceptibility to autoimmunity
SUMMARY In this perspective we outline a strategy for attenuating CD4 driven immunopathology by blockade of the TNF super family members, OX40L, and CD30L

Summary

Introduction

Cancer and autoimmunity are major causes of suffering and death, and a huge financial burden on health services worldwide. EVOLUTION OF THE PLACENTA – A NEW ORGAN The major advantage of placentation over oviparous forms of reproduction is that it greatly increases the chances of reproductive success by prolonging the parental protection of the developing offspring, including increasing the chance of surviving infection courtesy of a more mature immune system, initially supported by high affinity maternal IgG antibodies.

Results

Conclusion