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There is growing evidence that the multimodality approach targeting different facets of the immune system may possibly provide the best clinical benefit. This review centers on the utilization of therapeutic cancer vaccines with mainstream therapies including radiation, chemotherapy, and small molecule inhibitors. VX-661 Numerous immunomodulatory effects of mainstream treatments can be used to boost the antitumor activity caused by vaccines. For radiation therapy, these generally include a) upregulation of tumor antigens, costimulatory molecules, Fas, and major histocompatibility complex moieties, which makes tumors more vunerable to immune mediated attack; t) upregulation of cytokines, chemokines, and adhesion molecules, which enhances T cell trafficking to the tumor site and extends T cell/tumor contact; and c) downregulation of regulatory T cells, which facilitates generation of antigen specific T cells. Chemotherapys immunomodulatory Urogenital pelvic malignancy results include a) induction of immunogenic tumorcell death, leading to activation of dendritic cells and facilitating cross priming and tumor specific T cell generation; b) up-regulation of tumor antigens, adhesion substances, antigen processing machinery and MHC, which raises T cell recognition and causes T cell killing; and c) induction of leukopenia followed closely by differential homeostatic peripheral development that prefers tumor specific T cells. Eventually, select, focused SMIs can a) boost the number and function of tumor antigen specific T cells and reduce the number and function of myeloid derived suppressor cells and Tregs; b) stop the tumor cell cycle and cause apoptosis; and c) inhibit neoangiogenesis, regulate hypoxia, and stabilize tumor vasculature. Given the potential immunomodulatory effects Bortezomib of these established cancer therapies, combining them with cancer vaccines provides an opportunity to boost patient survival and standard of living. IMMUNOTHERAPY Radiation AND combining RADIATION THERAPY is the standard treatment for most cancer types, traditionally applied to locally eradicate tumor cells or modify tumor and/or tumor stroma structure with either curative or palliative intent. Even though local control of the main cyst is important and can usually reduce metastasis, radiation generally fails to control pre existing systemic illness, which may be present as undetectable micrometastases. Although radiation has broadly speaking been considered immunosuppressive, a few recent studies demonstrate that radiation actually has the potential to become immunomodulatory. Radiation-induced cell death is an immunologically active process where dying tumor cells launch tumor associated antigens that will potentially be used to stimulate robust tumor specific immune responses. Cells undergoing radiation induced cell death also create unique changes on their plasma membranes. These changes become danger signals to market phagocytosis by antigenpresenting cells such as macrophages and DCs.