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Ann Clin Trials Vaccines Res. 2017 | Volume 1 Issue 2
allied
academies
Global Vaccines & Vaccination Summit & B2B
November 01-02, 2017 | Toronto, Canada
Felix Fernandez Madrid
Wayne State University, USA
Autoimmunity in breast carcinogenesis: Implications for vaccination in solid tumors
Our findings of anti-mitochondrial and anti-centrosome
antibodies as well as autoantibodies targeting, RNA and
RNA-protein complexes, histones, idiotypes and molecules
involved in remodeling of the microenvironment in breast
cancer [BC] sera, support our proposal that autoimmunity
to tumor associated [TAA] and stromal associated antigens
[SAA] is involved in breast carcinogenesis. Autoimmunity is
mechanistically involved in the pathogenesis of rheumatic
autoimmune and organ-specific autoimmune diseases
by triggering chronic inflammation with consequent end-
organ tissue damage. It is generally accepted that chronic
inflammationmay lead to the development of cancer. Themost
effective anti-tumor immune responses in animal models as
well as in humans have relied on the efficient generation of TH1-
cell immunity that promotes CTL responses that would favor
tumor regression, while TH2 responses, i.e., autoantibodies
and cytokines have failed to provide a vigorous anti-tumor
effect. In this context, efforts to prevent and/or eradicate
solid tumors with the use of vaccination, although promising
have been largely disappointing. We have proposed that
autoimmunity to TAAs and SAAs is responsible for autoimmune
breast tissue damage, fueling chronic inflammation with
generation of tumorigenic signals providing the rationale for
the reported paradoxical association of B-cell hyperactivity and
BC progression. The proposed model of cancer progression
based on mitochondrial autoimmunity implies a vicious cycle
of mitochondria/ER stress, immune recognition of accumulated
unfolded or misfolded mitochondrial, centrosome and other
proteins by auto-reactive immune cells, autoimmune damage
of the target organ and chronic inflammation with generation
of tumorigenic signals. Autoantibodies in BC do identify
autoantigens participating in breast carcinogenesis. Some
autoantibodies and cytokines involved in immune surveillance
may have anti-tumor effects while others may be tumorigenic
and promote cancer progression. This model has the potential
ability of identifying protective and tumorigenic responses as
well as new candidate biomarkers for targeted immunotherapy
and for cancer vaccination in solid tumors.
Speaker Biography
Félix Fernández Madrid is a Professor of Internal Medicine at Wayne State University
in Detroit Michigan. His affiliations are Department of Internal Medicine, Center for
Molecular Medicine and Genetics, Karmanos Cancer Institute. Based on the established
role of autoantibodies as diagnostic and prognostic biomarkers in the rheumatic
autoimmune diseases [RADs] and on their involvement in disease pathogenesis he
became interested on a novel biomarker discovery approach which may contribute to
the diagnosis of BC and other solid tumors. Along with his team, they demonstrated
that autoantibodies in BC are not epiphenomena and that anti-mitochondrial
antibodies targeting subunits of mitochondrial electron transfer chain complexes I, IV
and V encoded by mtDNA are BC autoantigens, suggesting that these autoantibodies
are the expression of mitochondrial autoimmunity in BC. A major goal of his research
program is to establish the role of tissue damage produced by autoimmunity to breast
antigens as contributors to creating a chronic inflammatory milieu promoting the
progression of BC, and other solid tumors.
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