Healthy Donors Harbor Memory T Cell Responses to RAS Neo-Antigens

6 Citations (Scopus)


The RAS mutations are the most frequently occurring somatic mutations in humans, and several studies have established that T cells from patients with RAS-mutant cancer recognize and kill RAS-mutant cells. Enhancing the T cell response via therapeutic cancer vaccination against mutant RAS results in a clinical benefit to patients; thus, T cells specific to RAS mutations are effective at battling cancer. As the theory of cancer immuno-editing indicates that healthy donors may clear malignantly transformed cells via immune-mediated killing, and since T cells have been shown to recognize RAS-mutant cancer cells, we investigated whether healthy donors harbor T-cell responses specific to mutant RAS. We identified strong and frequent responses against several epitopes derived from the RAS codon 12 and codon 13 mutations. Some healthy donors demonstrated a response to several mutant epitopes, and some, but not all, exhibited cross-reactivity to the wild-type RAS epitope. In addition, several T cell responses were identified against mutant RAS epitopes in healthy donors directly ex vivo. Clones against mutant RAS epitopes were established from healthy donors, and several of these clones did not cross-react with the wild-type epitope. Finally, CD45RO+ memory T cells from healthy donors demonstrated a strong response to several mutant RAS epitopes. Taken together, these data suggest that the immune system in healthy donors spontaneously clears malignantly transformed RAS-mutant cells, and the immune system consequently generates T-cell memory against the mutations.

Original languageEnglish
Article number3045
Issue number10
Pages (from-to)1-16
Number of pages16
Publication statusPublished - 19 Oct 2020


  • Immune surveillance
  • Immuno-editing
  • Neo-antigens
  • RAS
  • T cell memory


Dive into the research topics of 'Healthy Donors Harbor Memory T Cell Responses to RAS Neo-Antigens'. Together they form a unique fingerprint.

Cite this