Cure Alveolar Soft Part Sarcoma International (iCureASPS)

"Abstract-

Advances in our understanding of autoimmunity and tumour immunity have led to improvements in immunotherapy for these diseases. Ironically, effective tumour immunity requires the induction of the same responses that underlie autoimmunity, whereas autoimmunity is driven by dysregulation of the same mechanisms that are involved in host defence and immune surveillance. Therefore, as we manipulate the immune system to treat cancer or autoimmunity, we inevitably unbalance the vital mechanisms that regulate self tolerance and antimicrobial resistance. This Science and Society article aims to dissect the conundrum that is inherent to the concept of immunotherapy and highlights the need for new and more specific therapeutic approaches.

The development of cancer and autoimmunity can be seen as a failure of the immune system to control tumour cell growth and to regulate autoreactive responses, respectively. The ability to reprogramme the immune system so that it will maintain homeostasis without the need for continuous treatment is the holy grail of therapies for these diseases. Conventional therapies for autoimmunity and cancer rely primarily on broad-spectrum suppressive regimens. The serious side effects of prolonged chemotherapy for the treatment of cancer or the harsh immuno-suppressive regimens for the treatment of autoimmune disease are well-known and have driven the continuing quest for more specific and less toxic therapies.

The immune system is finely balanced to distinguish foreign from self antigens. The process of thymic (central) tolerance eliminates high-affinity self-antigen-specific T cells, as well as those that fail to recognize self antigens entirely, and spares T cells that recognize self antigens with intermediate affinity. Because the naive immune repertoire is positively selected on self antigens, self recognition is hard-wired in the system and this blurs the boundaries between autoimmunity and immunity. Normally, peripheral tolerance keeps potentially autoreactive lymphocytes in check because recirculating lymphocytes are exposed to tissue antigens under non-inflammatory conditions, which results in a tolerant, anergic state. However, in the presence of stimuli that provide danger signals, such as infection and tissue damage, self tolerance can be broken and autoimmune disease may ensue. Conversely, a repertoire that is depleted of self-reactive cells may fail to provide effective recognition of growing cancers that express altered self antigens.

Similarly, autoimmunity and host anti-microbial immunity are inextricably linked, as effector responses that cause inflammatory tissue damage are the same ones that mediate effective host defence. Therefore, immunotherapeutic regimens that target common pathways of the immune system inevitably elicit both desirable and undesirable consequences. Strategies to eliminate cancer cells by breaking tolerance to self antigens can result in autoimmunity; conversely, suppressing immune function to inhibit autoimmune responses can compromise resistance to infection and allow for the development of malignancy1–5.

Approaches to therapy, both in cancer and in autoimmunity, can broadly be divided into the antigen-specific and the antigen-non-specific (BOX 1). Each has its advantages and its drawbacks, which affect the choice of therapy."



https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2764117/

Introduction
From an evolutionary point of view, the paramount goal of all living organisms is to survive, reproduce and propagate the species. In humans and most vertebrates, the mother has the responsibility to bear the most vulnerable of the species—the offspring, and protect it from danger, to accomplish this supreme mission. Additionally there is non-genetic passive transfer of immunity from mother to offspring called trans-generational immune priming. Therefore, having the parental role may account for stronger immunity in females to defend and “prepare” for this responsibility. Intriguingly, the same immune response shifts during pregnancy to “tolerate” the foreign fetus and prevent rejection. Interestingly, in most fish species the father bears the parental responsibility. The Syngnathidae group includes seadragons, pipefish and the iconic seahorse. In these species, while it is the mother who produces the eggs, the father carries, nurtures the eggs through gestation, and gives birth to the young thus fulfilling the parental and immune priming role. There is evidence that there are differences in the immune response in the male seahorse during the parental vs. mating phases with improved immunity during the parental stage (1, 2). These observations suggest that the parental role comes with great immune power and responsibility. A “side-effect” of the stronger immune response is the higher propensity for developing autoimmune disease. This may be a plausible perspective to understand the gender bias of autoimmune disease.

Sex hormones not only control the reproductive system, but also regulate the development, and function of the immune response. Innate and adaptive, humoral and cell-mediated immune responses are impacted by hormones, and dysregulation of these mechanisms contribute to immune-mediated diseases including autoimmune disease (3–9). While the exact molecular mechanisms of how female hormones regulate the immune system are yet incompletely elucidated, studies show that they control development, homeostasis, gene expression, and signaling processes in T and B lymphocytes to influence their function in health and disease. This review focuses on the role of sex hormones on the adaptive immune system and in autoimmune diseases with a focus on the prototype systemic autoimmune disease SLE (10–12).

https://www.frontiersin.org/articles/10 ... 02279/full