#COMPOSURE PRO SIDE EFFECTS PROFESSIONAL#
Leukocytes detect cell death through immune-based receptors for molecules released by dying cells (often termed “danger signals”), such as Toll-like receptor 4 (TLR4) and its ligands including the high-mobility group box 1 protein (HMGB1 Apetoh et al., 2007).Įffective anti-tumor therapy should induce sufficient tumor cell death in order to release tumor-associated antigens (TAAs) as well as danger signals attracting professional antigen-presenting cells (APCs) phagocytes to uptake and present tumor antigen for specific adaptive immunity. Both chemotherapy and RT impact growing cancers through their ability to induce cell death by disrupting various parameters of cell biology necessary for survival ( Haynes et al., 2008 Tesniere et al., 2008 Zitvogel et al., 2008).
RT is not always used alone and clinical translation of radiation therapies that incorporate immunotherapy must take into account their interaction with surgery or the multitude of chemotherapies. The abscopal bystander effect would be an important phenomenon, whether it is intended to target pre-existing distant metastases or to residual disease that was not removed by the primary therapy. In addition to the direct effect of radiation, focal radiation can have distant bystander effects that influence tumor growth outside of the irradiated region ( Ohba et al., 1998). Ionizing radiation is a powerful cytotoxic force that can be manipulated to specifically kill cancer cells at target sites. Over the course of radiation therapy (RT), patients have been shown to develop tumor antigen-specific immune responses that were not detectable before treatment demonstrating that immune suppression in cancer patients and any immune suppression caused by RT is relative rather than absolute ( Nesslinger et al., 2007).
Despite the presence of immune suppression, even multiply treated patients with significant tumor burden are capable of generating de novo tumor-specific immune responses ( Laheru et al., 2008). The host remains in a state of controlled immune activity, regulating the initiation and termination of immune responses to prevent widespread pathology is exploited by tumors to overcome the immunogenicity caused by their antigenicity and aggressive growth. Multiple inflammatory mechanisms control the location of immune responsiveness and serve to direct therapeutic responses to the site of immunological insult. There can be intense immune activity at mucosal surfaces and relative inactivity in closely neighboring sites. The immune system maintains a complex regulatory balance, maintaining immunological composure despite powerful immunological stimuli.
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