Specific immune cell and cytokine characteristics of human testicular germ cell neoplasia

Abstract

This study (and B.K. in person) was supported by the Deutsche Forschungsgemeinschaft (DFG) as part of the International Research Training Group between Justus Liebig University of Giessen and Monash University, Melbourne (GRK 1871/1) on 'Molecular pathogenesis on male reproductive disorders'. T.H., H.-C.S. and M.B. were supported by the LOEWE focus group 'MIBIE' (male infertility during infection & inflammation)-an excellence initiative of the German state government of Hessen. From the Australian side, K.L. was supported by NHMRC grants (Fellowship, ID1079646 and Project, ID1081987); K.L., S.I. and M.H. received scholarship (S.I.) and research funding (K.L., M.H.) from Monash University. The project also drew support from the Victorian Government's Operational Infrastructure Support Program. The authors have no competing interests to declare.

An in vitro model demonstrates the potential of neoplastic human germ cells to influence the tumour microenvironment

“…This is supported by changes in cytokine transcript levels, which are low in early-stage carcinoma in situ samples that harbour few GCNIS-containing tubules and infiltrating immune cells, but are significantly elevated in severely progressed testis cancer samples (Klein et al, 2016). This is supported by changes in cytokine transcript levels, which are low in early-stage carcinoma in situ samples that harbour few GCNIS-containing tubules and infiltrating immune cells, but are significantly elevated in severely progressed testis cancer samples (Klein et al, 2016).…”

“…However, many features characteristic of human TGCT are robustly expressed in the TCam-2 cell line, including expression of AP2c, OCT3/4, NANOG and others. The previously identified characteristics of ex vivo TGCT that comprise several different immune-stimulatory and immune cell-attracting cytokines (such as IL1B, IFNG, TNFA, CXCL13, CCL5; Klein et al, 2016) may likely lead to attraction and/or trapping of circulating immune cells at the (immune cell-favourable) tumour site. We and others have used this cell line to document responses to cell signalling and microenvironments in vitro and in vivo (Young et al, 2011;Nettersheim et al, 2015Nettersheim et al, , 2016.…”

“…Classification of immune cell subtypes present in TGCT by several investigators has yielded both concordant and contradictory interpretations (Bell et al, 1987;Nakanoma et al, 1992;Wei et al, 1992;Bols et al, 2000;Hvarness et al, 2013;Klein et al, 2016). Classification of immune cell subtypes present in TGCT by several investigators has yielded both concordant and contradictory interpretations (Bell et al, 1987;Nakanoma et al, 1992;Wei et al, 1992;Bols et al, 2000;Hvarness et al, 2013;Klein et al, 2016).…”

“…Testicular germ cell tumours (TGCT) can be characterized as immunological tumours, with large numbers of infiltrating lymphocytes commonly detected during routine pathological evaluation of biopsy samples from testis cancer patients. Classification of immune cell subtypes present in TGCT by several investigators has yielded both concordant and contradictory interpretations (Bell et al, 1987;Nakanoma et al, 1992;Wei et al, 1992;Bols et al, 2000;Hvarness et al, 2013;Klein et al, 2016). Importantly, the role and immunological activity of these cells remain largely unknown.…”

Association of IL-6 Gene (-174 and -572 G/C) Polymorphisms with Proliferative Diabetic Retinopathy of Type 2 Diabetes in a Chinese Population

“…In the aforementioned study, IL-6 and IL-8 levels were elevated in the vitreous of patients with PDR or proliferative vitreoretinopathy, which suggests that IL-6 and IL-8 might play an important role in the pathogenesis of PDR and proliferative vitreoretinopathy [20] . IL-6 has also been regarded as a critical proinflammatory cytokine in cardiovascular or immune related disorders [22,23] . It has been reported that IL-6 knockout alleviates the upregulation of TGF-β 1 in the hearts of diabetic mice [24] .…”