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Cancer
Immunity, Vol. 5, p. 8 (6 June 2005)
Submitted: 29 April 2005. Accepted: 29 April 2005.
Contributed by: H Schreiber
Rapid destruction of the tumor microenvironment
by CTLs recognizing cancer-specific antigens
cross-presented by stromal cells
Michael T. Spiotto and Hans Schreiber
Department of Pathology and the Committee on Immunology,
The University of Chicago, Chicago, IL 60637, USA
Keywords:
mice, antigen presentation, stromal cells, cytotoxic T lymphocytes, tumor escape
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Abstract
A single tumor contains a heterogeneous population of cancer cells. Some cancer cells express antigens and are susceptible to specific CTLs. However, other cancer cells are antigen-loss variants (ALVs) that escape these CTLs because they express little or no antigen. Here, we show that antigen-specific T cells can eliminate ALVs when the parental population expresses a model gp33 antigen (KAVYNFATM) at a level sufficient to be locally cross-presented by the nonmalignant stromal cells. That is, the ALVs are eliminated as bystanders because the stroma is destroyed. ALVs escape bystander killing when the bone marrow-derived and/or non-bone marrow-derived stroma does not express the appropriate MHC or when the amount of antigen is too low for effective cross-presentation. The rapid destruction of the stroma, including bone marrow-derived as well as sessile components, and of the parental cancer cells, may be essential for the complete rejection of established tumors by preventing variant escape.
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