Non-specific immunotherapy has been for a long time a standard treatment option for patients with metastatic renal cell carcinoma but was redeemed by specific targeted molecular therapies, namely the VEGF and mTOR inhibitors. After moving treatment for mRCC to specific molecular agents with a well-defined mode of action, immunotherapy still needs this further development to increase its accuracy. Nowadays, an evolution from a rather non-specific cytokine treatment to sophisticated targeted approaches in specific immunotherapy led to a re-launch of immunotherapy in clinical studies. Recent steps in the development of immunotherapy strategies are discussed in this review with a special focus on peptide vaccination which aims at a tumor targeting by specific T lymphocytes. In addition, different combinatory strategies with immunomodulating agents like cyclophosphamide or sunitinib are outlined, and the effects of immune checkpoint modulators as anti-CTLA-4 or PD-1 antibodies are discussed.

BackgroundMalignant germ cell tumours are the most common malignant tumours in young men. They are histologically divided into seminomas and non-seminomas. Non-seminomas are further subdivided into embryonic carcinomas, yolk sac tumours, chorionic carcinomas, and teratomas. For the therapeutic management it is essential to differentiate between these histological subtypes.MethodsInvestigated cases included normal testis (n = 50), intratubular germ cell neoplasia (n = 25), seminomas (n = 67), embryonic carcinomas (n = 56), yolk sac tumours (n = 29), chorionic carcinomas (n = 2), teratomas (n = 7) and four metastases of YST’s for their CK19 expression. In addition Leydig cell- (n = 10) and Sertoli cell- tumours (n = 4) were included in this study.ResultsAll investigated seminomas, embryonic carcinomas as well as normal testis and intratubular germ cell neoplasias did not express CK19. In contrast, all investigated yolk sac tumours strongly expressed CK19 protein. These findings became also evident in mixed germ cell tumours consisting of embryonic carcinomas and yolk sac tumours, although CK19-expression could also be observed in analysed chorionic carcinomas and epithelial components of teratomas.ConclusionCK19 proved to be a sensitive marker to identify yolk sac tumours of the testis and to distinguish them from other germ cell tumours, especially seminomas and embryonic carcinomas.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4075546891400979.

Integrin-mediated cell adhesion and signaling is essential to vascular development and inflammatory processes. Elevated expression of integrin ␣ v ␤ 3 has been detected in ischemia-reperfusion injury and rejecting heart allografts. We thus hypothesized that the inhibition of ␣ v -associated integrins may have potent antiinflammatory effects in acute kidney allograft rejection. We studied the effects of a peptidomimetic antagonist of ␣ v integrins in two rat models of renal allotransplantation, differing in degree of major histocompatibility complex mismatch. Integrin ␣ v ␤ 3 was up-regulated in rejecting renal allografts. Integrin antagonist reduced the histological signs of acute rejection, the intensity of the mononuclear cell infiltration, and cell proliferation in the grafted kidneys. This could be correlated to a reduced leukocyte-endothelial interaction and an improved peritubular microcirculation observed by intravital microscopy. In vitro under laminar flow conditions, the arrest of monocytes to interleukin-1␤-activated endothelium was decreased. Furthermore, in co-culture models the proliferation and transmigration of monocytes/macrophages, endothelium, and fibroblasts induced by renal tubular epithelia was efficiently inhibited by ␣ v integrin antagonism. These data reveal an important role of this integrin subclass in leukocyte recruitment and development and maintenance of acute rejection; blockade of ␣ v integrins may provide a new therapeutic strategy to attenuate acute allograft rejection.

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