Visualizing the course of antigen-specific CD8 and CD4 T cell responses to a growing tumor

Ludger Klein, Lydie Trautman, Stelios Psarras, Silke Schnell, Anja Siermann, Roland Liblau, Harald von Boehmer, Khashayarsha Khazaie

Research output: Contribution to journalReview article

44 Scopus citations

Abstract

Spontaneous tumors frequently express antigens that can be recognized by the immune system but nevertheless manage to evade immune surveillance. To better understand the mechanism of evasion, we followed CD8 and CD4 T cells reacting against a subcutaneously growing tumor, modified to express influenza hemagglutinin (HA) as surrogate tumor antigen. Adoptive transfer of 8,000 antigen-specific CD8 T cells was sufficient to protect against challenge with 1×106 tumor cells, while larger numbers of T cells rejected established tumors. HA-specific CD4 T cells could not reject tumors on their own but helped rejection by CD8 T cells. Rejection of the tumor coincided with prolonged survival of expanded antigen-specific CD8 and CD4 T cells, while a failing anti-tumor response was accompanied by transient expansion followed by rapid elimination of antigen-specific T cells. Thus, a highly immunogenic tumor can evade immune surveillance because of an insufficient number of tumor-specific T cells and antigen overload, resulting in exhaustion of the immune response. In this scenario, adoptive immunotherapy rather than vaccination promises successful treatment.

Original languageEnglish (US)
Pages (from-to)806-814
Number of pages9
JournalEuropean Journal of Immunology
Volume33
Issue number3
DOIs
StatePublished - Mar 1 2003

Keywords

  • Antigen
  • CD4/CD8
  • Exhaustion
  • Immune response
  • T cell
  • Tumor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Klein, L., Trautman, L., Psarras, S., Schnell, S., Siermann, A., Liblau, R., von Boehmer, H., & Khazaie, K. (2003). Visualizing the course of antigen-specific CD8 and CD4 T cell responses to a growing tumor. European Journal of Immunology, 33(3), 806-814. https://doi.org/10.1002/eji.200323800