Cancer Uses the Common Morphogenesis Source of the Host

Trophic properties of hematopoietic stem cells can influence the malignant growth alternatively to immune control. The annual growth of the body mass by age in adult populations of welfare countries used as the most common criterion of metabolic and proliferative tissue activity, and these data compared with death’ rate for malignant and somatic diseases in different age-groups of the same countries. The rate of physiologic involution of different cell populations in the lymphoid lineage by age also involved in corre-lations between the above parameters. A decrease in death rate for cancer and increase it’s for non-malignant diseases found in 60+ populations, which have the lowest physiological temp of renewal of lymphocytes number and mass of the body. The lack of both the thymus gland volume and proliferative activity of naive lymphocytes reduces physiological body mass renewal as well as the cancer death rate but enhances somatic death rate, opposing to anticancer immunity at large. A protumor character of the lymphopoietic system’s relation with malignancy seems more realistic than defending one.


Introduction
Though cancer-immune model has reached 12 types of immune cells, 13 types of cytokines, and 107 interaction links nowadays, the complexity of the model considers underestimated yet [1] [2], partly because the practical input of immuno-oncology is scanty. As for autonomous cancer immunotherapy, endless attempts at the clinical level remain just promising until now [3]. During the long Open Journal of Biophysics of maximal validity by Excel program. Each part of the curve described by the exponential equation: S = Ae λt , where S is the current value, t is elapsed time in years, A is the initial value at t = 0, and λ is the constant exponential rate of changes per year for the given period It (λ) can be positive (+) or negative (¬). It was suitable for comparing periods because λ-value is independent of value A and is constant throughout of whole period. The maximal coefficient of determination R 2 used for the goodness of fitting of the function to the data. The p-value for R ± mR calculated according to the equation for Student's t-test [15]:
The dynamic of mean BW by age, similar to that on Figure 1, we calculated for the Germany population too, using data extracted from [20]. year. Probability p ≤ 0.05, ≤0.01, and ≤0.001 marks with asterisks *, **, and ***correspondently. Open Journal of Biophysics The highest exponential growth rate for young males and females, according to [20] [21], correspond to speed body weight growth from ≈2 kg to 73 -60 kg.
This speed growth of the young accompanies by speed waist of a thymus size and basal metabolism after their short overshoot to 2 -4 years age [22]. The decline of thymus size is titled lymphoid type of postnatal growth of the organs of human body because only lymphoid tissue reveals involution during adolescence. This unique lymphoid tissue involution and concomitant fast increasing in wight of the fat-free body during adolescence might be considered as result of lymphopoietic resource' consumption for growth of the other tissues. The highest basal metabolism and the highest rate of its followed spending λ = ¬0.016 and ¬0.023 for boys and girls [23] confirm such opportunity. In oppose, the cells of the adult body reproduce themselves for a while as necessary to substitute the defective or dying cells during 17 -55/60 years and then stop gradually growing and dividing in 60+ old in parallel with basal metabolism' decline with λ = ¬0.003 per year for males and females, that is much slower than in a growing young's [23].
The described regularities are compared with age-dependent lymphopoiesis.
The human longevity depends on lymphopoietic system injury, according to classic radiobiologic term-hematopoietic syndrome [24] [25] [26] [27]. Figure   2 shows a natural age-dependence of the main lymphopoietic features for cell immunity of healthy people both combined sexes. Figure 2. Exponential decline of humans lymphopoiesis parameters (y) by natural age (x), according to the equation: y = Ae −λx . Data for curves 1 -6 extracted from [28]. Data for size of solid thymic glands both types: with ≥50% (curve 7) and ≥90% of active parenchyma (curve 8) extracted from [29]. Data for sjTREC molecules number per naïve T cell extracted from [30]. Data for CD34 + HSC per 1 ml of BM extracted from [31] and [32]. Open Journal of Biophysics and ¬0.121 for number of sjTREC molecules in naive T cells (curve 9, p = 0.008). Figure 2 shows the most specific influence of the naïve lymphocytes in BM and thymus (curves 7 and 8) and molecular witness of their proliferation-circularized DNA elements (sjTREC) [35]-on age. These cells originate in BM, migrate in blood and thymus during intensive growth of the body mass up to 17 -18 age. Comparison of Figure 1 and Figure 2 identifies young lymphoid descendant of HSC as the most responsible cells for natural viability. During the period from 18 to 60 age, the thymus has involuted completely, providing slow BW growth 10 -12 kg only at the lowest exponential growth rates λ = 0.0026 -0.0046 per year ( Figure 1). The final period of life 60+ accompanied with scanty generation of TdT+ lymphoid stem cells in BM only [36]. This deficit accompanies by loss of the BW (with negative λ) and accelerated loss of survival with λ = ¬0.1 (males) and ¬0.06 (females) in comparing with ¬0.0001 and ¬0.0008 before 60+ age. More than 90% death of the population aged 60+ (Figure 1) associate with a deficit of T reg cells as well, as HSC and naïve lymphoid cells (Figure 2), and the association points on their universal property to promote the regeneration of different tissue.
That function of lymphoid cells is defined earlier as morphogenic/trophic/ feeding property. It associates partly with the marker of lymphoid stem cells-terminal deoxynucleotidyl transferase (TdT). This Na-dependent enzyme, in extracellular media, polymerizes free deoxynucleotides into oligonucleotides. The TdT appears in the media by apoptosis of young lymphocytes and facilitates the DNA reparation/regeneration' processes by nonsense-DNA fragments, produced by the enzyme. They re-utilize by target cells via pinocytosis much easy than single deoxynucleotides charged negatively [37] [38] [39]. Later the TdT enzyme discussed as one of three markers for the lymphoblasts, namely CD34 and CD133 markers [40], and as a component of proliferation in different tissues [41] [42]. The TREC and TdT enzyme both marks newly generated thymocytes in the cortex of the thymus gland [43], and part of these cells have a CD31 marker [43] that is typical for angiogenic properties [45]. Their deficit reduced angiogenesis and suggested as a probable reason for tumorigenesis inhibition by age [5]. This suggestion is in concordance with higher survival patients with lower presence of vascular endothelial growth factor (VEGF) in a growing tumor of early stages T1-2 [46]. The young lymphoid descendants may be committed Open Journal of Biophysics (aimed) also toward injured tissues needed for reparation [47] [48]. The specificity of lymphopoietic lineage of feeding elements (curves 7, 8, and 9) accentuates by their speeder decline in comparison with the multilineage ancestor CD34+ HSC (curve 10). Thus, the strong suppression in the progenitor pool of lymphocytes and a moderate decrease in a bulk cells number discredit the remodeling matured CD4+ and CD4− cells as an only reason the weakening of tumorigenesis in advanced age supposed by [5]. The small size cells with surface markers CD133+, CD34+ have a real stem nature and a lymphocyte-like appearanceas well as their descendants. The presence of more young, smallest embryonic-like stem cells (VSELs) in adult tissues and their morphogenic properties is a substantial challenge also to the dominated dogma of cellular immune defense from cancer [49].

Is the Age-Dependent Exhaustion of an Immunity
Protumor or Anti-Tumor?   and CD34+/CD133+/CXCR4+ with age registered later [55]. Simultaneously, a percentage of death from heart and cerebrovascular diseases among all non-cancer increases fifth times from 40 to 60 age, whereas the average percentage from 20 to 40 age did not change [56]. A six-seven times reduction of the average percentage of VSEL (very small embryonic-like) CD133+ stem cells in epicardium and endocardium of the heart was in people 40 -60 age vs. 20 -40 age. Transplantation of these cells after acute and chronic myocardial infarction demonstrated their therapeutic potential [57]. It was consistent with last world statistic. For example, in 2017 the cancer was a course of death for 1.05, 3.96 and 4.43 million of people in age groups 15 -49, 50 -69 and 70+, whereas the 2.36, 8.08 and 17.42 million died from non-malignant pathologies, including cardiovascular, respiratory, kidney digestive, diarrheal diseases, and lower respiratory infections [58]. A deficit of common morphogenic resource presented by angiogenic HSC and young lymphocytes seems to be the most logical reason for six-time reduction of world cancer death together with slight-in one and sixth tenths time-enhance of non-cancer death after 69 age. Relative excessive risks of cancer incidence and cancer mortality for a cohort of Russian Chernobyl emergency workers with mean age 33.9 years, at entry into the zone of recovery operations increased to 51 years old but to 59 years old mortality has lowered though the incidence continued to rise [59]. Thus, the best available justification for the sharp turn of curves in Figure 3 is an abrupt deficit of lymphatic lineage of hematopoiesis between 40 -60 age.

Conclusion
Thus, a protumor character of the lymphopoietic system's relation with malignancy seems more realistic than defending one. We did not find reasons for supporting the stimulation of anticancer immunity by any cytotoxic treatment, including long time metronomic therapy with low doses of anticancer drugs, as argued by Calabrese EJ and followers [70]. Analysis of the phenomenon of radiation hormesis showed that it does not disprove a linear hypothesis, being a result of redirection of morphogenic potency of the host from cancer tissue' growth to reparation/regeneration of the multitude of sub-lethal injures in non-malignant tissues of the body [71]. Giving low doses of cytotoxic chemotherapy may act that indirect way, simulating direct inactivation of cancer cells due to insufficiency of tumor endothelial net renewal [72]. We support the actuality of the changing paradigm of tumor response to different kinds of cytotoxic agent also [72] [73]. With this review, we try to initiate the discussion, should the immune doctrine in oncology continue to elongate an endless range of new mechanisms at cellular and molecular levels, or attempt to re-evaluate and subdue them to general physiological phenomena at the level of the whole organism of the host.