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<p>Contrary to expectations based on their higher cell numbers, larger and longer-lived species do not face dramatically increased risk of cancer. This strongly suggests that evolution has fashioned natural cancer resistance mechanisms, yet our knowledge remains limited on what these mechanisms might be. The cancer immunological surveillance hypothesis, proposed by Burnet and Thomas in the 1950s, highlights immunity as a key factor determining species-specific cancer resistance. Here we address the original, evolutionary interpretation of this hypothesis by investigating the relationship between cancer mortality risk and markers of efficient antigen presentation. Our results show that the expansion of the MHC class I gene complex, as well as increased selection for diversity at these genes is associated with sharply decreasing cancer mortality risk across mammals. This suggests that the efficient presentation of diverse peptides in somatic cells is important for cancer suppression across mammals, providing pioneering evidence that supports the cancer immunosurveillance hypothesis across species.</p>

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Immunological surveillance against cancer across mammals

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月24日

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  • Orsolya Vincze,
  • Piotr Minias,
  • Alexandre Corthay,
  • Fernando Colchero,
  • Jean-François Lemaître,
  • Louise Maille,
  • Tamás Malkócs,
  • Justus Hagemann,
  • Dalia A. Conde,
  • Samuel Pavard,
  • Antoine M. Dujon,
  • Beata Ujvari,
  • Frédéric Thomas,
  • Amy M. Boddy,
  • Carlo C. Maley,
  • Damien Chevallier,
  • Tuul Sepp,
  • Thomas Pradeu,
  • Mathieu Giraudeau

摘要

Contrary to expectations based on their higher cell numbers, larger and longer-lived species do not face dramatically increased risk of cancer. This strongly suggests that evolution has fashioned natural cancer resistance mechanisms, yet our knowledge remains limited on what these mechanisms might be. The cancer immunological surveillance hypothesis, proposed by Burnet and Thomas in the 1950s, highlights immunity as a key factor determining species-specific cancer resistance. Here we address the original, evolutionary interpretation of this hypothesis by investigating the relationship between cancer mortality risk and markers of efficient antigen presentation. Our results show that the expansion of the MHC class I gene complex, as well as increased selection for diversity at these genes is associated with sharply decreasing cancer mortality risk across mammals. This suggests that the efficient presentation of diverse peptides in somatic cells is important for cancer suppression across mammals, providing pioneering evidence that supports the cancer immunosurveillance hypothesis across species.