Abstract
Background: The unavoidable links between the benefits of conventional systemic treatment of cancer and the side effects such as lymphopenia. Objective: To analyze this phenomenon in view of the newly discovered trophic function of circulating hematopoietic stem cells (HSC) and their lymphocyte descendants. Method: We used population statistics and recent current research involving natural aging and preliminary aging with cancer, its cytotoxic therapy, eclampsia at pregnancy, and radiation hormesis. Results: In contrast to immune-defense interpretations of these health conditions, the trophic influence of HSC and morphogenic lymphocytes on natural tissue renewal and regeneration after sublethal injuries eliminates the majority of covered inconsistencies, which are inherent to the dominating idea of cellular immunity. Conclusion: Our examination led to the feeding influence of lymphopoiesis on tumor progression, an indirect mechanism of tumor growth control by systemic therapy via either destruction of trophic cells, or by competitive distraction from malignant tissue via reparation of sublethal injuries in normal tissues. Analyses also involved similarities of the mechanisms of systemic chemotherapy and total body/half body radiotherapy in low doses, as well as the futility of the theoretical opposition of the radiation hormesis phenomenon to the linear non-threshold model, dominant in radiobiology.
Highlights
N/L ratio (NLR) positively correlates with aging in the healthy population [30], and the ratio increases sufficiently during multiple organ dysfunction syndrome (MODS) [31] [32] due to deadly lymphopenia with concomitant reduced innate γ-δ T cells, which are able to migrate to different epithelial tissues [33]
Because chemotherapy and radiation both induce similar types of DNA damage for cell cycle arrest throughout of the body, there is no strong argument for overestimation of the therapeutic efficiency of systemic chemotherapy or for the underestimation of TBI/HBI therapeutic approaches
A lowered resource of generation of trophic lymphoid stem cells is in agreement with a lowered incidence/mortality/prevalence of cancer during the last decades of life
Summary
Morphogenic migratory cells (MC) include the ancestral and angiogenic CD133+HSC, progenitor CD34+HSC, and young emigrating cells from the BM and thymus like the terminal deoxynucleotidyl transferase-positive (TdT+) prelymphocytes, descendant CD31+ angiogenic T-lymphocytes, and other “regulatory” cells [2] [8] [11] [12] [13] [14] These MC may become committed to their own tissues with different histotypes [5] [15] [16] [17], and their abilities to potentiate regeneration, reparation, and cell renewal in target organs compromise the use of lymphocytes against tumors as a “foreign invader”. MF opens up an opportunity for new explanations of numerous viability phenomena in the fields of aging, pregnancy, malignancy, cancer treatment, radiobiology, and transplantology All these situations are associated with systemic chronic inflammation (SCI), which is characterized by two opposite processes involving neutrophilia (N) and lymphopenia (L). Lymphopoiesis is a vulnerable system in mammals, and lymphopoietic reproductive capacity is the most amortizable among other physiological tissue systems in the thymus, BM, gastrointestinal tract, breast, ovary, skin, lung, kidney, liver, adrenal, adipose tissue, muscle, bone, and brain, which could all be responsible for the natural involution of the organism [20]
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