Chronic Inflammation: Synergistic Interactions of Recruiting Macrophages (TAMs) and Eosinophils (Eos) with Host Mast Cells (MCs) and Tumorigenesis in CALTs. M-CSF, Suitable Biomarker for Cancer Diagnosis!

Abstract

Ongoing debates, misunderstandings and controversies on the role of inflammation in cancer have been extremely costly for taxpayers and cancer patients for over four decades. A reason for repeated failed clinical trials (90% ± 5 failure rates) is heavy investment on numerous genetic mutations (molecular false-flags) in the chaotic molecular landscape of site-specific cancers which are used for “targeted” therapies or “personalized” medicine. Recently, unresolved/chronic inflammation was defined as loss of balance between two tightly regulated and biologically opposing arms of acute inflammation (“Yin”–“Yang” or immune surveillance). Chronic inflammation could differentially erode architectural integrities in host immune-privileged or immune-responsive tissues as a common denominator in initiation and progression of nearly all age-associated neurodegenerative and autoimmune diseases and/or cancer. Analyses of data on our “accidental” discoveries in 1980s on models of acute and chronic inflammatory diseases in conjunctival-associated lymphoid tissues (CALTs) demonstrated at least three stages of interactions between resident (host) and recruited immune cells: (a), acute phase; activation of mast cells (MCs), IgE Abs, histamine and prostaglandin synthesis; (b), intermediate phase; down-regulation phenomenon, exhausted/degranulated MCs, heavy eosinophils (Eos) infiltrations into epithelia and goblet cells (GCs), tissue hypertrophy and neovascularization; and (c), chronic phase; induction of lymphoid hyperplasia, activated macrophages (Mϕs), increased (irregular size) B and plasma cells, loss of integrity of lymphoid tissue capsular membrane, presence of histiocytes, follicular and germinal center formation, increased ratios of local IgG1/IgG2, epithelial thickening (growth) and/or thinning (necrosis) and angiogenesis. Results are suggestive of first evidence for direct association between inflammation and identifiable phases of immune dysfunction in the direction of tumorigenesis. Activated MFs (TAMs or M2) and Eos that are recruited by tissues (e.g., conjunctiva or perhaps lung airways) whose principal resident immune cells are MCs and lymphocytes are suggested to play crucial synergistic roles in enhancing growth promoting capacities of host toward tumorigenesis. Under oxidative stress, M-CSF may produce signals that are cumulative/synergistic with host mediators (e.g., low levels of histamine), facilitating tumor-directed expression of decoy receptors and immune suppressive factors (e.g., dTNFR, IL-5, IL-10, TGF-β, PGE2). M-CSF, possessing superior sensitivity and specificity, compared with conventional markers (e.g., CA-125, CA-19-9) is potentially a suitable biomarker for cancer diagnosis and technology development. Systematic monitoring of interactions between resident and recruited cells should provide key information not only about early events in loss of immune surveillance, but it would help making informed decisions for balancing the inherent tumoricidal (Yin) and tumorigenic (Yang) properties of immune sy...

Cancer and inflammation

“…The monocytes can differentiate into macrophages when they enter the tissue and also phagocytose cells and debris. Macrophages help orchestrate adaptive immunity by producing both pro- and anti-inflammatory factors (46, 56, 96). New blood vessels are also created in inflammatory responses.…”

Safety concerns and hidden agenda behind HPV vaccines: another generation of drug‐dependent society?

“…made American health status at the bottom of other healthy nations [1][2][3]. 1,2,3,4,5 The abusive power of establishment intensified since 1971, when the Cancer Act, signed by President Nixon, increased cancer research funding of National Cancer Institute (NCI)/NIH to 1.6 B, so that cancer problem be solved in 8 years! The establishment has been successful in collecting/spending several trillions of dollars from public and private resources ($1.6 trillion spent in 2008 alone on research, drug development, clinical trials and care) with claims of 'targeted' therapy, 'precision' or 'personalized' medicine, including the recent failed attempts for 'immunotherapy' [1].…”

Density of tryptase-positive mast cells correlated with the presence of H. pylori in gastric neoplasia

“…A first analysis of the results in Tables 3 and 4 allowed the conclusion of a highly significant mobilization of mast cells in tumor invasion fronts (present in 66.66% of cases in LTIF area and 73.33% of cases in DTIF area); these findings might imply that the presence of mast cells is the host's response to tumorigenesis-induced changes in order to limit their extension [25,26]; this idea (protective role of mast cells against tumor-induced alterations) is also supported by the increased number of mast cells in the gastric wall distantly located from tumor (NGW).…”