The immune/
inflammation system potentially serves to arrest, eliminate or promote
tumor development. Nonetheless, factors that dictate the choice are not comprehensively known yet. Using a B16/F1 syngeneic wild type model, we evaluated the essentiality of initial transformed cells' density for overt
tumor development, the molecular trends of inflammatory mediators in the normal
tumor-adjacent epithelial tissues (NTAT), and how such local events may reflect systematically in the host. Overt
tumors developed, within an observatory period of at least 45 days and 90 days at most, only in mice inoculated with
cancer cells above a limiting threshold of 1× 10(3) cells. Immunoblots showed early, intense and transient presence of IL-1β, IFN-γ, and both the all-
thiol and
disulfide forms of
HMGB1 in the NTAT of non-
tumor bearing mice. However, all-
thiol form of
HMGB1 and delayed but aberrant
IL-6 expression characterized chronic
inflammation in
tumor bearing hosts. These local epithelial tissue events uniquely reflected in host's systemic
cytokines dynamics where stable Th1/Th2 signature (IFN-γ/ IL-4) coupled with early Th1 cells polarization (
IL-12/ IL-4) evidenced in non-
tumor hosts but highly fluctuating Th1/ Th2 profile in
tumor hosts, even before
tumors became overt. This hypothesizes that the physical quantum of transformed cells that may either spontaneously arise or accrue at a locus may be crucial in orchestrating the mechanism for the type of local epithelial tissue and systemic immune/ inflammatory responses essential for
tumor progression or arrest.