Expression of a "self-"antigen by human tumor cells enhances tumor antigen-specific CD4+ T-cell function

Christopher E. Touloukian, Wolfgang W. Leitner, Paul F. Robbins, Yong F. Li, Xiaoqiang Kang, Rejean Lapointe, Patrick Hwu, Steven A. Rosenberg, Nicholas P. Restifo

Research output: Contribution to journalArticlepeer-review

Abstract

CD4+ T cells can recognize "self" tumor antigens, but the impact of tumor cell expression of self-antigens on CD4+ T-cell function in humans is unknown. Here, we identify a new epitope (ISPNSVFSQWRVVCDSLEDYD) derived from tyrosinase-related protein-1 (TRP-1) using a predictive algorithm and mice transgenic for a chimeric HLA-DRB1*0401 molecule. We then compared the functions of TRP-1-epitope-specific, CD4+ T-cell responses in normal healthy individuals to those found in patients with metastatic malignant melanoma. Surprisingly, we found that tumor-bearing patients had significantly higher levels of TRP-1-specific, CD4+ T-cell function than healthy volunteers as measured ex vivo. Thus, the net effect of "self" antigen expression by tumor cells was the enhancement of tumor antigen-specific CD4+ T-cell function, rather than immunosuppression. These findings indicate that antigens expressed by malignant melanoma cells can partially activate CD4+ T lymphocytes.

Original languageEnglish (US)
Pages (from-to)5144-5147
Number of pages4
JournalCancer Research
Volume62
Issue number18
StatePublished - Sep 15 2002

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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