| A new model for the genesis of human cancer
Our
studies prompted us to introduce a new model for the genesis of human
cancer. We suggest that the development of cancer requires infection(s)
during which antigenic determinants from pathogens mimicking self-antigens
are co-presented to the immune system, leading to breaking T cell
tolerance. Autoreactive T cells must be eliminated by apoptosis when the
immune response is terminated. Apoptosis can be deficient in the event of
a weakened immune system, the causes of which are multifactorial. Some
autoreactive T cells suffer genomic damage in this process, but manage to
survive. The
resulting cancer stem cell still retains some functions of an inflammatory
T cell, so it seeks out sites of inflammation inside the body. Due to its
defective constitutive production of inflammatory cytokines and other
growth factors, a stroma is built at the site of inflammation similar to
the temporary stroma built during wound healing. The cancer cells grow
inside this stroma, forming a tumor that provides their vascular supply
and protects them from cellular immune response. As
cancer stem cells have plasticity comparable to normal stem cells,
interactions with surrounding normal tissues cause them to give rise to
all the various types of cancers, resembling differentiated tissue types.
Immunosuppressive cancer therapies inadvertently re-invigorate pathogenic
microorganisms and parasitic infections common to cancer, leading to a
vicious circle of infection, autoimmunity and malignancy that ultimately
dooms cancer patients. Based on this new understanding, we recommend a
systemic approach to the development of cancer therapies that supports
rather than antagonizes the immune system.
Bibliographical reference:
Peter Grandics A-D Research Foundation, Carlsbad, CA 92008, USA
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