CD4+ T lymphocytes infiltrating human breast cancer recognise autologous tumor in an MHC-class-II restricted fashion

Roya Dadmarz, Magdalene K. Sgagias, Steven A. Rosenberg, Douglas J. Schwartzentruber

Research output: Contribution to journalArticlepeer-review

Abstract

Tumor-infiltrating lymphocytes (TIL) were derived from primary breast tumors, metastatic lymph nodes and malignant pleural effusions from 34 patients with breast cancer. TIL were cultured for approximately 30 days and studied for phenotype, cytotoxicity, and the ability to secrete cytokines in response to autologous tumor stimulation. Tumor specimens were obtained from two different sites in 7 patients, resulting in 41 samples from which 38 TIL cultures were established. In addition to screening 38 bulk TIL cultures, TIL from 21 patients were separated into CD4+ and CD8+ subsets and extensively studied. Three CD4+ TIL were found specifically to secrete granulocyte macrophage-colony-stimulating factor and tumor necrosis factor α when stimulated by autologous tumor and not by a large panel of stimulators (24-34) consisting of autologous normal cells, allogeneic breast or melanoma tumors and EBV-B cells. This cytokine release was found to be MHC-class-II-restricted, as it was inhibited by the anti-HLA-DR antibody L243. These 3 patients' EBV-B cells, when pulsed with tumor lysates, were unable to act as antigen-presenting cells and induce cytokine secretion by their respective CD4+ TIL. These findings demonstrate that MHC-class-II-restricted CD4+ T cells recognising tumor-associated antigens can be detected in some breast cancer patients.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalCancer Immunology Immunotherapy
Volume40
Issue number1
DOIs
StatePublished - Jan 1 1995

Keywords

  • Breast cancer
  • CD4 T cells
  • Cytokine secretion
  • MHC-class-II-restriction

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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