Evolving strategies for cancer and autoimmunity: back to the future

Area of Science:

• Evolutionary immunology
• Mammalian reproductive strategies
• Autoimmunity and cancer pathogenesis

Background:

• Current research on autoimmunity and cancer susceptibility focuses on genetic and environmental factors.
• An alternative perspective suggests that the evolution of the human immune system, driven by reproductive success, underlies susceptibility.
• Immune system adaptations in early placental mammals, linked to placentation, are key to this evolutionary view.

Purpose of the Study:

• To explore the hypothesis that human susceptibility to autoimmunity and cancer is an evolutionary consequence of immune system adaptations.
• To investigate the co-evolution of immune components like high-affinity antibodies and CD4 memory with mammalian placentation.
• To identify potential therapeutic targets by dissecting immune genes and proteins involved in these evolutionary changes.

Main Methods:

• Comparative analysis of immune system evolution in mammals.
• Dissection of immunologically active genes and proteins associated with placentation.
• Exploration of the regulatory mechanisms of the immune system in the context of evolutionary pressures.

Main Results:

• High-affinity antibodies and CD4 memory, along with their regulation, co-evolved with placentation in mammals.
• Immune adaptations evolved for reproductive success may have unintended consequences for individual health.
• Understanding these evolutionary trade-offs offers insights into immune system regulation.

Conclusions:

• Human susceptibility to autoimmunity and cancer may be an evolutionarily acceptable side effect of immune adaptations for reproduction.
• De-tuning specific arms of the immune system could abrogate autoimmune responses while preserving infection defense.
• A paradoxically 'detuned' immune system might enhance anti-tumor responses against cancers.