Der Urologe (Impact Factor: 0.44). 01/2012; 51(1):44-49. DOI: 10.1007/s00120-011-2712-6
Die Immuntherapie und Tumorzellvakzinierung ist eine herausfordernde Therapieoption beim Prostatakrebs, zumal Nebenwirkungen
nur selten auftreten. In diesem Review werden aktuelle Entwicklungen in der Vakzinierungstherapie des Prostatakarzinoms diskutiert.
Die FDA-genehmigte antigenpräsentierende Zellvakzine Sipuleucel-T wird im Detail beschrieben, ebenso wie neue Strategien in
der Immuntherapie wie die der RNA und Peptidvakzinierung. Derzeit ist der Erfolg einer Prostatakrebsvakzinierung immer noch
mit Einschränkungen verbunden. Die immunsuppressive Wirkung des Tumors im lokalen Mikroenvironment und die Ausbildung regulatorischer
T-Zellen, die das Immunsystem in seiner Effektorfunktion unterdrücken, limitieren den Therapieerfolg. Das Konzept der immunologischen
„Schnittstellen-Checkpointmodulation“ beschreibt die gezielte Beeinflussung immunologischer Schnittstellen, um Toleranzmechanismen
zu durchbrechen und die Immunantwort zu steigern. Mögliche klinische Mechanismen einer Checkpointmodulation werden skizziert.
Immune therapy and tumor cell vaccination is a challenging option in prostate cancer therapy, especially as side effects rarely
occur. This review highlights recent developments in vaccination therapy of prostate cancer. The FDA approved antigen presenting
cell vaccine Sipuleucel-T is described and new strategies of immune therapy like RNA and peptide vaccination are discussed
in detail. Currently the effect of prostate cancer vaccination has still limitations, at least partially due to the immune
suppressive effects of the tumor microenvironment and regulatory T cells, which suppress the immune effector function. To
overcome these hurdles the concept of immune checkpoint modulation, which has the aim to break tolerance mechanisms, is discussed.
Potential clinical therapies of checkpoint modulation are outlined.
SchlüsselwörterProstatakarzinom–Vakzinierung–T-Zell-Aktivierung–Mikroenvironment des Tumors–Sipuleucel-T
KeywordsProstate carcinoma–Vaccination–T-cell activation–Specific immune therapy–Sipuleucel-T
[Show abstract][Hide abstract] ABSTRACT: Tumors express antigens that should induce immune-mediated rejection, but spontaneous rejection of established tumors is rare. Recent work demonstrates that one reason for the lack of tumor rejection is that tumors actively defeat host immunity. This concept forces us to rethink current approaches to harnessing potent, specific host immunity to battle cancer, most of which are based on the paradigm that inducing more antitumor immune cells alone is therapeutic. However, as I discuss in this Personal Perspective, a newer paradigm predicts that reducing tumor-driven immune suppression will be clinically beneficial. CD4+CD25+ Tregs are one mechanism of tumor-driven immune evasion that provide prototypical targets for testing novel anticancer treatment strategies within the newer paradigm.
[Show abstract][Hide abstract] ABSTRACT: Mononuclear phagocytes are versatile cells that can express different functional programs in response to microenvironmental signals. Fully polarized M1 and M2 (or alternatively activated) macrophages are the extremes of a continuum of functional states. Macrophages that infiltrate tumor tissues are driven by tumor-derived and T cell-derived cytokines to acquire a polarized M2 phenotype. These functionally polarized cells, and similarly oriented or immature dendritic cells present in tumors, have a key role in subversion of adaptive immunity and in inflammatory circuits that promote tumor growth and progression.
Trends in Immunology 12/2002; 23(11):549-55. DOI:10.1016/S1471-4906(02)02302-5 · 10.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The cancer immunoediting hypothesis has gained significant footing over the past decade as a result of work performed using sarcomas induced by 3-methylcholanthrene (3-MCA) in mice. Despite the progress made by several groups in establishing evidence for the three phases of immunoediting (elimination, equilibrium and escape), there continues to be active controversy on the nature of interaction between spontaneously formed tumour cells and the immune system during the early phases of tumourigenesis. At the root of this controversy is conflicting and unresolved evidence spanning back to the 1970s regarding the incidence and frequency of 3-MCA-induced sarcomas in immunocompetent mice as compared to immunodeficient mice. In this mini review we provide a critical analysis of both sides of this controversy.
British Journal of Cancer 09/2009; 101(3):381-6. DOI:10.1038/sj.bjc.6605198 · 4.84 Impact Factor
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