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

Publication ,  Journal Article
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 in: J Exp Med
January 22, 2007

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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Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

January 22, 2007

Volume

204

Issue

1

Start / End Page

49 / 55

Location

United States

Related Subject Headings

  • T-Lymphocytes, Cytotoxic
  • Stromal Cells
  • Receptors, Antigen, T-Cell
  • Neoplasms, Experimental
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • In Vitro Techniques
  • Immunology
  • Immunization
 

Citation

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Zhang, B., Bowerman, N. A., Salama, J. K., Schmidt, H., Spiotto, M. T., Schietinger, A., … Schreiber, H. (2007). Induced sensitization of tumor stroma leads to eradication of established cancer by T cells. J Exp Med, 204(1), 49–55. https://doi.org/10.1084/jem.20062056
Zhang, Bin, Natalie A. Bowerman, Joseph K. Salama, Hank Schmidt, Michael T. Spiotto, Andrea Schietinger, Ping Yu, et al. “Induced sensitization of tumor stroma leads to eradication of established cancer by T cells.J Exp Med 204, no. 1 (January 22, 2007): 49–55. https://doi.org/10.1084/jem.20062056.
Zhang B, Bowerman NA, Salama JK, Schmidt H, Spiotto MT, Schietinger A, et al. Induced sensitization of tumor stroma leads to eradication of established cancer by T cells. J Exp Med. 2007 Jan 22;204(1):49–55.
Zhang, Bin, et al. “Induced sensitization of tumor stroma leads to eradication of established cancer by T cells.J Exp Med, vol. 204, no. 1, Jan. 2007, pp. 49–55. Pubmed, doi:10.1084/jem.20062056.
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. Induced sensitization of tumor stroma leads to eradication of established cancer by T cells. J Exp Med. 2007 Jan 22;204(1):49–55.

Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

January 22, 2007

Volume

204

Issue

1

Start / End Page

49 / 55

Location

United States

Related Subject Headings

  • T-Lymphocytes, Cytotoxic
  • Stromal Cells
  • Receptors, Antigen, T-Cell
  • Neoplasms, Experimental
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • In Vitro Techniques
  • Immunology
  • Immunization