Abstract
The 37-kDa immature laminin receptor protein (iLRP) is a speciesconserved, universal immunogenic protein that is expressed in all thus-far examined embryonic and early fetal cells of inbred and outbred rodents. It has also been identified in human concepti. It is altered through normal maturation processes to become a non-immunogenic 67-kDa dimeric mature laminin receptor protein (mLRP) in mid-to late gestation in the mammalian fetus. This antigen ceases to be expressed as an active autoimmunogen in the full-term fetus and in the normal differentiating tissues and organs of the neonate or adult organism, apparently due to dimerization, but it is re-expressed as an immunogenic monomer in tumor cells. In this review, we highlight the known mechanisms of immune responses with particular emphasis on the possible role of the 37-kDa oncofetal antigen/immature laminin receptor (OFA/iLRP) in both pregnancy and cancer.
Highlights
The fetus represents a foreign entity to the maternal immune system, this “natural” allograft is not normally rejected
The IL-10 released by these T suppressor (Ts) lymphocyte clones could impair the anti-fetal cytotoxicity of T cytotoxic (Tc) lymphocytes, secreting interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), which are specific for immature laminin receptor protein (iLRP) and possibly all Tc lymphocytes capable of killing fetal cells, including those directed against paternal major histocompatibility complex (MHC) antigens (Fig. 1)
Immature rather than mature LRP appears to play a significant role in regulating host tumor resistance by stimulating anti-iLRP-specific cytotoxic Tc lymphocyte subclasses and anti-iLRP specific Ts and Th1 T-cell responses during tumor development in vivo [19, 20, 30]. iLRP in high doses stimulates CD8 suppressor T-cell (Ts) lymphocytes which secrete IL-10 [19]
Summary
The fetus represents a foreign entity to the maternal immune system, this “natural” allograft is not normally rejected. Galectin-3, a component of the mature laminin receptor protein (mLRP) may function as an immune regulator to inhibit T-cell immune responses and promote tumor growth, providing a new mechanism for immune tolerance [23].
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