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Genome Doubling Shields Ovarian Tumors From Immune Attack and Drives Their Evolution

Researchers are pursuing treatments that target genome-doubled cells following evidence of their role in immune evasion.

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Overview

  • Single-cell DLP sequencing of over 30,000 cells from 70 tumors identified WGD-high status in more than 65% of HGSOC cases.
  • WGD-high tumors actively repress the STING pathway, dampening innate immune activation despite high chromosomal instability.
  • Evolutionary mapping placed genome doubling as a recurring event that can occur early or late and even multiple times within individual tumors.
  • Increased chromosome loss and micronuclei formation after doubling underscore the link between WGD and metastasis potential.
  • Next steps include development of WGD-targeted therapies and investigation of fallopian tube microenvironment triggers.