TUMOR FACTORS AND IMMUNITY DURING PRENEOPLASIA/NEOPLASIA

Project: Research project

Description

Using a murine mammary tumor syngeneic to BALB/c mice (D1-DMBA-3) we have
previously documented profound changes in the immune system correlating
with increasing tumor burden. Some of the phenotypic and functional
alterations are due to, at least in part, to the production of
immunomodulatory cytokines by the tumor. We have shown that GM-CSF is
constitutively produced by the D1-DMBA-3 tumor and that it promotes the
appearance and/or expansion of a population of aberrant macrophages capable
of downregulating the immune responses of tumor bearing mice. The proposed
studies will analyze whether animals implanted with preneoplastic lesions
from which the D1-DMBA-3 tumor was derived, also display altered parameters
of immunity. Likewise, the immune responses of these mice after
progression of the preneoplastic lesions to established neoplasia will be
studied. These phenotypic and functional characterizations will be
performed not only using cells of the peripheral organs but also with
tumor-infiltrating lymphoreticular cells. The production of cytokines,
such as GM-CSF, by the preneoplastic lesions or mammary tumors developed
from then in BALB/c mice, will be assessed. Likewise, the causes for the
loss of tumoricidal potential of peritoneal exudate macrophages from tumor
bearing mice will be studied. The mechanisms of downregulation of GM-CSF-
induced macrophages present in mammary tumors (and in preneoplastic lesions
if they occur) will be explored. Although GM-CSF is used to replenish
depleted bone marrow cells after chemotherapy and radiation, the long term
consequences of such treatment are unknown. Therefore, the elucidation of
the role of this molecule in the immune system of mice bearing
preneoplastic or tumor tissues will lead to a rational approach to the
administration of this factor to cancer patients. furthermore, these
studies will provide new insight into the modulatory effects of the immune
responses in the progression from preneoplasia to fully developed
neoplasms.
StatusFinished
Effective start/end date3/18/922/29/96

Funding

  • National Institutes of Health: $186,561.00
  • National Institutes of Health
  • National Institutes of Health

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Immunity
Granulocyte-Macrophage Colony-Stimulating Factor
9,10-Dimethyl-1,2-benzanthracene
Neoplasms
Breast Neoplasms
Immune System
Down-Regulation
Macrophages
Cytokines
Peritoneal Macrophages
Exudates and Transudates
Tumor Burden
Bone Marrow Cells
Radiation
Drug Therapy
Population

ASJC

  • Medicine(all)