Induced sensitization of tumor stroma leads to eradication of established cancer by T cells

Bin Zhang, Natalie A. Bowerman, Joseph K. Salama, Hank Schmidt, Michael T. Spiotto, Andrea Schietinger, Ping Yu, Yang Xin Fu, Ralph R. Weichselbaum, Donald A. Rowley, David M. Kranz, Hans Schreiber

Research output: Contribution to journalArticle

Abstract

Targeting cancer cells, as well as the nonmalignant stromal cells cross-presenting the tumor antigen (Ag), can lead to the complete destruction of well-established solid tumors by adoptively transferred Ag-specific cytotoxic T lymphocytes (CTLs). If, however, cancer cells express only low levels of the Ag, then stromal cells are not destroyed, and the tumor escapes as Ag loss variants. We show that treating well-established tumors expressing low levels of Ag with local irradiation or a chemotherapeutic drug causes sufficient release of Ag to sensitize stromal cells for destruction by CTLs. This was shown directly using high affinity T cell receptor tetramers for visualizing the transient appearance of tumor-specific peptide-MHC complexes on stromal cells. Maximum loading of tumor stroma with cancer Ag occurred 2 d after treatment and coincided with the optimal time for T cell transfer. Under these conditions, tumor rejection was complete. These findings may set the stage for developing rational clinical protocols for combining irradiation or chemotherapy with CTL therapy. JEM

Original languageEnglish (US)
Pages (from-to)49-55
Number of pages7
JournalJournal of Experimental Medicine
Volume204
Issue number1
DOIs
StatePublished - Jan 22 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Zhang, B., Bowerman, N. A., Salama, J. K., Schmidt, H., Spiotto, M. T., Schietinger, A., Yu, P., Fu, Y. X., Weichselbaum, R. R., Rowley, D. A., Kranz, D. M., & Schreiber, H. (2007). Induced sensitization of tumor stroma leads to eradication of established cancer by T cells. Journal of Experimental Medicine, 204(1), 49-55. https://doi.org/10.1084/jem.20062056