In vivo priming of two distinct antitumor effector populations

The role of MHC class I expression

Hyam I. Levitsky, Audrey J Lazenby, Robert J. Hayashi, Drew M. Pardol

Research output: Contribution to journalArticle

175 Citations (Scopus)

Abstract

Downregulation of major histocompatibility complex (MHC) class I expression is an important mechanism by which tumors evade classical T cell- dependent immune responses. Therefore, a system was designed to evaluate parameters for active immunization against MHC class I- tumors. Mice were capable of rejecting a MHC class I- tumor challenge after immunization with an irradiated granulocyte/macrophage colony-stimulating factor (GM-CSF) transduced MHC class I- tumor vaccine. This response was critically dependent on CD4+ T cells and natural killer (NK) cells, but minimally on CD8+ T cells. A strong protective response against MHC class I+ variants of the tumor could be elicited when mice were immunized with irradiated MHC class I+ GM-CSF-secreting tumor cells. This response required CD4+ and CD8+ T cells, and in addition, elimination of NK cells resulted in outgrowth of tumors that had lost expression of at least one MHC class I gene. Finally, class I MHC expression on the vaccinating cells inhibited the response generated against a MHC class I- tumor challenge. These results demonstrate that the host is capable of being immunized against a tumor that has lost MHC class I expression and reveal conditions under which distinct effector cells play a role in the systemic antitumor immune response.

Original languageEnglish (US)
Pages (from-to)1215-1224
Number of pages10
JournalJournal of Experimental Medicine
Volume179
Issue number4
DOIs
StatePublished - Apr 1 1994
Externally publishedYes

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Major Histocompatibility Complex
Population
Neoplasms
T-Lymphocytes
Granulocyte-Macrophage Colony-Stimulating Factor
Natural Killer Cells
MHC Class I Genes
Cancer Vaccines
Immunization
Vaccination
Down-Regulation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

In vivo priming of two distinct antitumor effector populations : The role of MHC class I expression. / Levitsky, Hyam I.; Lazenby, Audrey J; Hayashi, Robert J.; Pardol, Drew M.

In: Journal of Experimental Medicine, Vol. 179, No. 4, 01.04.1994, p. 1215-1224.

Research output: Contribution to journalArticle

Levitsky, Hyam I. ; Lazenby, Audrey J ; Hayashi, Robert J. ; Pardol, Drew M. / In vivo priming of two distinct antitumor effector populations : The role of MHC class I expression. In: Journal of Experimental Medicine. 1994 ; Vol. 179, No. 4. pp. 1215-1224.
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