Induced Sensitization of Tumor Stroma Leads to Eradication of Established Cancer by T Cells

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2007 Jan 11

PMID 17210731

Citations 202

Authors

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

Affiliations

Soon will be listed here.

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.

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