Exuberated numbers of tumor-specific T cells result in tumor escape.
Cytotoxic T cells (CTL) play a major role in tumor rejection. Expansion of CTLs, either by immunization or adoptive transfer, is a prominent goal in current immunotherapy. The antigen-specific nature of these expansion processes inevitably initiates a clonotypic attack on the tumor. By injecting an Ovalbumin-expressing melanoma into OT-I mice, in which >90% of CTLs recognize an Ovalbumin peptide, we show that an increased number of tumor-specific CTLs causes emergence of escape variants. We show that these escape variants are a result of antigen silencing via a yet undetermined epigenetic mechanism, which occurs frequently and is spontaneously reversible. We further show that an increase in the time of tumor onset in OT-I compared with C57BL/6J is a result of immune selection.
Goldberger
Ofir
O
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Volovitz
Ilan
I
Machlenkin
Arthur
A
Vadai
Ezra
E
Tzehoval
Esther
E
Eisenbach
Lea
L
D019264:Adoptive Transfer; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D020868:Gene Silencing / Q000502:physiology; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology*; D008546:Melanoma, Experimental / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000235:genetics; D010047:Ovalbumin / Q000235:genetics; D017393:RNA Editing / Q000276:immunology / Q000502:physiology; D013601:T-Lymphocytes / Q000473:pathology*; D019139:Tumor Escape / Q000276:immunology*
D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D009363:Neoplasm Proteins; C476587:Taa1 protein, mouse; D010047:Ovalbumin