Extra-Lymphatic Solid Tumor Growth Is Not Immunologically Ignored and Results in Early Induction of Antigen-Specific T-Cell Anergy: Dominant Role of Cross-Tolerance to Tumor Antigens

Alex Cuenca, Fengdong Cheng, Hongwei Wang, Jason Brayer, Pedro Horna, Lingping Gu, Harold Bien, Ivan M. Borrello, Hyam I. Levitsky, Eduardo M. Sotomayor

Research output: Contribution to journalArticle

94 Scopus citations

Abstract

A better understanding of how solid malignancies arise in an immunocompetent host, avoid immune recognition, and ultimately progress to widely disseminated cancer is essential to effectively harness the immune system against solid tumors. Because of their extra-lymphatic localization, it has been proposed that solid malignancies are just ignored by the immune system, thereby allowing their uncontrolled growth and dissemination. Alternatively, as most of the solid tumors are unable to express costimulatory molecules, the "signal one without signal two" model of tolerance induction has been frequently evoked to account for the failure of the immune system to reject antigenic tumors in vivo. In this study, we showed, however, that the extra-lymphatic growth of solid tumors is not immunologically ignored by the lymphoid compartment, resulting instead in the early induction of antigen-specific CD4+ T-cell tolerance. Furthermore, analysis of parent-into-F1 bone marrow (BM) chimeras demonstrates that presentation of tumor antigens by BM-derived antigen-presenting cells represents the dominant mechanism in solid tumor-induced CD4+ T-cell tolerance. Our findings of early development of antigen-specific T-cell unresponsiveness mediated by BM-derived antigen-presenting cells, not only provides a plausible explanation for the failure of the immune system to reject antigenic solid tumors in vivo, but more importantly, they have identified a barrier that, if appropriately manipulated, may lead to approaches to effectively harness the immune system against solid malignancies.

Original languageEnglish (US)
Pages (from-to)9007-9015
Number of pages9
JournalCancer research
Volume63
Issue number24
StatePublished - Dec 15 2003

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Cuenca, A., Cheng, F., Wang, H., Brayer, J., Horna, P., Gu, L., Bien, H., Borrello, I. M., Levitsky, H. I., & Sotomayor, E. M. (2003). Extra-Lymphatic Solid Tumor Growth Is Not Immunologically Ignored and Results in Early Induction of Antigen-Specific T-Cell Anergy: Dominant Role of Cross-Tolerance to Tumor Antigens. Cancer research, 63(24), 9007-9015.