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Identification of activated tumor antigen-reactive CD8+ cells in healthy individuals

T V Lee1, B W Anderson, G E Peoples

  • 1Department of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.

Oncology Reports
|April 18, 2000
PubMed

Insights

Tumor-associated lymphocytes (TALs) in healthy individuals can be activated by HER-2 peptide E75, producing interferon-gamma (IFN-γ). This suggests a role for these T cells in natural immunosurveillance against tumors.

Area of Science:

  • Immunology
  • Cancer Research
  • Cellular Biology

Background:

  • Tumor-associated lymphocytes (TALs) play a role in anti-tumor immunity.
  • The HER-2 peptide E75 is an immunodominant CTL epitope found in ovarian and breast cancers.
  • Understanding the activation of CD8+ T cells by tumor antigens is crucial for cancer immunotherapy.

Purpose of the Study:

  • To investigate the ability of the HER-2 peptide E75 to activate effector functions in CD8+ T cells from healthy individuals.
  • To compare the immune response to E75 with responses to other tumor antigens and an influenza peptide.
  • To explore the potential for natural immunosurveillance mediated by tumor antigen-reactive CD8+ T cells.

Main Methods:

  • Freshly isolated CD8+ cells and peripheral blood mononuclear cells (PBMCs) from healthy donors were stimulated with tumor-associated antigen (TAA) peptides, including E75, folate binding protein (FBP), and amino-enhancer of split of Notch (AES).
  • Interferon-gamma (IFN-γ) and Interleukin-2 (IL-2) production by CD8+ cells, and IL-12 production by antigen-presenting cells (APCs) were measured.
  • Responses were compared to those induced by the influenza matrix peptide (M1: 58-66) and assessed for dose-dependency and co-stimulation effects.

Main Results:

  • HER-2 peptide E75 rapidly induced IFN-γ in CD8+ cells from 5 out of 6 healthy donors within 20-24 hours, with detectable levels as early as 6 hours.
  • IFN-γ induction was antigen concentration-dependent and observed with other tumor peptides (FBP, AES) and HLA-A2 matched tumor cells.
  • E75-reactive CD8+ cells induced lower levels of IL-12 and IFN-γ compared to M1 peptide responses, and alphaB7.1 co-stimulation enhanced IL-2 production.

Conclusions:

  • Freshly isolated CD8+ T cells from healthy individuals possess the capacity to respond to tumor-associated antigens like HER-2 peptide E75.
  • The presence of tumor antigen-reactive CD8+ T cells suggests a potential mechanism for natural immunosurveillance.
  • These findings contribute to understanding immune regulation by tumors and may inform the development of cancer immunotherapies.

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