Tumour-reactive T cell subsets in the microenvironment of ovarian cancer

Br J Cancer. 2019 Feb;120(4):424-434. doi: 10.1038/s41416-019-0384-y. Epub 2019 Feb 5.

Abstract

Background: Solid malignancies are frequently infiltrated with T cells. The success of adoptive cell transfer (ACT) with expanded tumour-infiltrating lymphocytes (TILs) in melanoma warrants its testing in other cancer types. In this preclinical study, we investigated whether clinical-grade TILs could be manufactured from ovarian cancer (OC) tumour specimens.

Methods: Thirty-four tumour specimens were obtained from 33 individual patients with OC. TILs were analysed for phenotype, antigen specificity and functionality.

Results: Minimally expanded TILs (Young TILs) were successfully established from all patients. Young TILs contained a high frequency of CD3+ cells with a variable CD4/CD8 ratio. TILs could be expanded to clinical numbers. Importantly, recognition of autologous tumour cells was demonstrated in TILs in >50% of the patients. We confirmed with mass spectrometry the presentation of multiple tumour antigens, including peptides derived from the cancer-testis antigen GAGE, which could be recognised by antigen-specific TILs. Antigen-specific TILs could be isolated and further expanded in vitro.

Conclusion: These findings support the hypothesis that patients with OC can benefit from ACT with TILs and led to the initiation of a pilot clinical trial at our institution .

Trial registration: clinicaltrials.gov: NCT02482090.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • CD4-CD8 Ratio
  • Female
  • Humans
  • Immunophenotyping
  • Interferon-gamma / pharmacology
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Ovarian Neoplasms / immunology*
  • Ovarian Neoplasms / therapy
  • T-Lymphocyte Subsets / immunology*
  • Tumor Microenvironment*

Substances

  • Interferon-gamma

Associated data

  • ClinicalTrials.gov/NCT02482090