Identification of a mutated fibronectin as a tumor antigen recognized by CD4+ T cells: Its role in extracellular matrix formation and tumor metastasis

Helen Y. Wang, Juhua Zhou, Kuichun Zhu, Adam I. Riker, Francesco M. Marincola, Rong Fu Wang

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

CD4+ T cells play an important role in orchestrating host immune responses against cancer, particularly by providing critical help for priming and extending the survival of CD8+ T cells. However, relatively little is known about major histocompatibility complex class II-restricted human tumor antigens capable of activating CD4+ T cells. Here, we describe the identification of a mutated fibronectin (FN) as a tumor antigen recognized by human histocompatibility leukocyte antigen-DR2-restricted CD4+ T cells. Deoxyribonucleic acid (DNA) sequencing analysis indicated that this gene contains a mutation that results in the substitution of lysine for glutamic acid and gives rise to a new T cell epitope recognized by CD4+ T cells. Tumor cells harboring the mutant FN resulted in the loss of FN matrix formation and the gain of metastatic potential based on the migration pattern compared with that of tumor cells that express wildtype FN. Additional experiments using cell lines stably expressing the mutated FN cDNA demonstrated that the point mutation in FN was responsible for the loss of FN staining in extracellular matrices and the enhancement of tumor cell migration. These findings represent the first demonstration that a mutated gene product recognized by CD4+ T cells is directly involved in tumor metastasis, which indicates the importance of CD4+ T cells in controlling the spread of tumor cells to distant anatomic sites.

Original languageEnglish (US)
Pages (from-to)1397-1406
Number of pages10
JournalJournal of Experimental Medicine
Volume195
Issue number11
DOIs
StatePublished - Jun 3 2002

Keywords

  • Antitumor immunity
  • Cancer biology
  • Cancer vaccines
  • CD4 T cells
  • Immunotherapy

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of 'Identification of a mutated fibronectin as a tumor antigen recognized by CD4<sup>+</sup> T cells: Its role in extracellular matrix formation and tumor metastasis'. Together they form a unique fingerprint.

Cite this