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Memory T cells targeting oncogenic mutations detected in peripheral blood of epithelial cancer patients

Gal Cafri1, Rami Yossef1, Anna Pasetto1

  • 1Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.

Nature Communications
|January 27, 2019
PubMed

Insights

Researchers detected T cells targeting cancer mutations in the blood of metastatic cancer patients. This finding supports developing personalized T cell therapies for epithelial cancers.

Area of Science:

  • Immunology
  • Oncology
  • Cancer Research

Background:

  • T cells targeting shared oncogenic mutations can lead to durable tumor regression in epithelial cancer patients.
  • While T cells are found in tumor-infiltrating lymphocytes, their presence in peripheral blood of metastatic epithelial cancer patients remains unconfirmed.

Purpose of the Study:

  • To investigate the detectability of T cells targeting somatic mutations in the peripheral blood of patients with metastatic epithelial cancers.
  • To explore the potential of these peripheral T cells for developing personalized T cell-based cancer immunotherapies.

Main Methods:

  • Utilized highly sensitive in vitro stimulation and cell enrichment techniques.
  • Analyzed peripheral memory T cells from six metastatic cancer patients.
  • Identified and isolated CD4+ and CD8+ memory T cells targeting specific mutated KRAS variants (KRASG12D, KRASG12V) and other neoantigens (SMAD5, MUC4).

Main Results:

  • Successfully identified and isolated CD4+ and CD8+ memory T cells targeting mutated KRAS variants in three out of six patients.
  • Detected CD8+ neoantigen-specific T cells targeting mutated SMAD5 and MUC4 proteins in two additional metastatic colon cancer patients.
  • Demonstrated the presence of T cells reactive to both shared and unique somatic mutations in the peripheral blood.

Conclusions:

  • Peripheral blood memory T cells targeting somatic mutations are detectable in epithelial cancer patients.
  • These findings suggest a potential avenue for developing personalized T cell-based cancer immunotherapies applicable across multiple patients.

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