The Journal of Experimental Medicine
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Published online
doi:10.1084/jem.20062056
The Journal of Experimental Medicine, Vol. 204, No. 1, 49-55
The Rockefeller University Press, 0022-1007 $30.00
© Zhang et al.
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BRIEF DEFINITIVE REPORT

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

Bin Zhang1, Natalie A. Bowerman3, Joseph K. Salama2, Hank Schmidt2, Michael T. Spiotto1, Andrea Schietinger1, Ping Yu1, Yang-Xin Fu1, Ralph R. Weichselbaum2, Donald A. Rowley1, David M. Kranz3, and Hans Schreiber1

1 Department of Pathology and Committee on Immunology and 2 Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL 60637
3 Department of Biochemistry, University of Illinois, Urbana, IL 61801

CORRESPONDENCE Bin Zhang: bzhang2{at}uchicago.edu OR Hans Schreiber: hszz{at}uchicago.edu

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.


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