December 13, 2021
IT CAUSES THE BODY TO “TREAT” THE ENDOTHELIUM PRECISELY AS A CANCER THERAPY – BY DESTROYING IT WHILE CAUSING MASSIVE INLAMMATION AND IMMUNE CELL INFILTRATION.
First, let us look at what Cancer does. Cancer wants an Anergic Endothelium. It wants an Endothelium which WILL NOT REACT. It will not cause the Endothelium to activate so that immune cells will not be “attracted” to it and remove it. It also wants to create new blood vessels to feed it. This combination of “problems” it has can be easily remedied – by destroying it. Indeed, THIS IS A RECENT THERAPEUTIC UNDER DEVELOPMENT.
The following certainly is COVID-19. Would you not agree?
One important physiological function of normal endothelial cells is quiescence of the inflammatory response and thus, participation in immune surveillance. Quiescent endothelial cells fail to provide the requisite signals for leukocyte recruitment; but the cells can be activated to express adhesion molecules and to release chemokines that promote capture and transmigration of blood leukocytes into tissues. Endothelial cell activation can typically induced by multiple factors, including circulating inflammatory cytokines, such as tumor necrosis factors (TNF) and interleukins (IL), reactive oxygen species, oxidized low density lipoprotein, autoantibodies and traditional risk factors directly and indirectly activate endothelial cells. The term activated endothelium implies a change in endothelial cell morphology. Endothelial activation was further specified as a change in surface molecules and in endothelial cell functions in response to cytokine treatment, and it was emphasized that these changes does not represent endothelial cell injury or dysfunction. Components of endothelial cell activation are upregulation of surface antigens (e.g., HLA molecules) and leucocyte adhesion molecules (e.g., E-selectin, ICAM-1/2, and VCAM-1), pro-thrombotic endothelial cell changes (e.g., loss of the surface anticoagulant molecules thrombomodulin and heparan sulfate), cytokine production (e.g., IL6, IL8, MCP1), and changes in the vascular tone (e.g., loss of vascular integrity, expression of vasodilators, and NO). These components mutually interact in causing local inflammation. Endothelial activation also leads to an increase in angiopoietin-2, which is known to destabilize barrier function and promote inflammation (26). The recruited and extravasated immune cells appear then in vicinity of the activated endothelial cells, and can further become activated. Importantly, the phenotype of activated endothelial cell is reversible and can return to the quiescent, non-activated phenotype when the activating factors were removed. Prolonged activation of the endothelium can be associated with the loss of microvascular barrier integrity and subsequent vascular injury or progress to endothelial cell apoptosis.
Now, let us turn our attention to current tumor therapy theory.
The different approaches being currently explored to increase recruitment of immune effector cells, include manipulating the expression of homing-associated molecules on T-cells and tumor endothelial cells. In a very elegant preclinical study Elia et al. showed that a selective (PRE)ACTIVATION OF THE TUMOR ENDOTHELIUM WITH THE CYTOKINE TNF promoted intratumoral T-cell infiltration, and IMMUNE CHECKPOINT BLOCKADE.
And, does this not sound familiar? NGR-TNF administration was already used as a safe and therapeutic systemic administration to target TNF selectively to angiogenic tumor vessels which then altered the endothelial barrier function together with an upregulation of leukocyte-endothelial cell adhesion molecules, the release of pro-inflammatory cytokines, and the infiltration of tumor-specific effector CD8(+) T-cells.
And, most interestingly: Finally, the combined therapy had beneficial effects on endogenous immune surveillance, THROUGH DEPLETION OF REGULATORY T-CELLS and expansion of a fully functional, polyclonal repertoire of cytotoxic T-lymphocytes.
Is the entire body being viewed as a tumor?
The Tumor Vascular Endothelium as Decision Maker in Cancer Therapy