CELL MEDIATED IMMUNITY IN MAMMARY TUMOR MODELS

Project: Research project

Project Details

Description

The long term objective of this proposal is to elucidate the
interrelationships between the immune effector cells of Balb/c mice and
their interactions with syngeneic mammary tumors of viral and non-viral
origin developing in these hosts. The model systems to be employed include
the Balb/cCrgl mouse colony where only endogenous mouse mammary tumor virus
(MMTV) is present, Balb/cfC3H mice where in addition to the endogenous
virus the exogenous MMTV has been introduced by foster nursing, and a
colony of immunodeficient Balb/c mice which includes mice with inherited
asplenia and heterozygous for the nude gene that have been shown to possess
a very high incidence of spontaneous mammary tumors at an early age. The
expression of MMTV-related antigens in lymphocytes will be analyzed at the
transcriptional and translational levels in the Balb/cCrgl, Balb/cfC3H and
in the immunodeficient Balb/c mice of the various genotypes. The relevance
of endogenous MMTV as well as the modulating effects of exogenous virus to
the host immune defenses will be assessed. Various regulatory cells
detected in our previous studies that affect the responses to MMTV and to
tumor associated antigens (TAA), will be analyzed by morphological, surface
marker characteristics and functional activities. The mechanisms of action
governing several cytotoxic reactions, i.e. NK, ADCC and innocent bystander
cytotoxicity, will be scrutinized in the context of their effector cells,
modulating factors and alterations during tumor growth. The possible
reasons for the lack of responsiveness to TAA of the tumor infiltrating
lymphocytes will be investigated. The proposed studies, which are logical
derivations of our ongoing program, will help our understanding of the
relative contributions of the various viral and tumor antigenic moieties
and of the different types of lymphoreticular cells to the final outcome of
the host-tumor interactions.
StatusFinished
Effective start/end date1/1/903/31/94

Funding

  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute

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