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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Zhang, B; Bowerman, NA; Salama, JK; Schmidt, H; Spiotto, MT; Schietinger, A; Yu, P; Fu, Y-X; Weichselbaum, RR; Rowley, DA; Kranz, DM; Schreiber, H

Published Date

  • January 8, 2007

Published In

Volume / Issue

  • 204 / 1

Start / End Page

  • 49 - 55

PubMed ID

  • 17210731

Pubmed Central ID

  • 17210731

Electronic International Standard Serial Number (EISSN)

  • 1540-9538

International Standard Serial Number (ISSN)

  • 0022-1007

Digital Object Identifier (DOI)

  • 10.1084/jem.20062056

Language

  • eng