Gayer Fabian A, Henkel Miriam, Luft Juliane, Reichardt Sybille D, Fichtner Alexander, Legler Tobias J, Reichardt Holger M
Institute for Cellular and Molecular Immunology, University Medical Center Göttingen, 37073 Göttingen, Germany.
Clinic of Urology, University Medical Center Göttingen, 37075 Göttingen, Germany.
Cancers (Basel). 2023 May 5;15(9):2619. doi: 10.3390/cancers15092619.
Testicular germ cell cancer (TGCC) is subdivided into several subtypes. While seminomatous germ cell tumors (SGCT) are characterized by an intensive infiltration of immune cells which constitute a pro-inflammatory tumor micromilieu (TME), immune cells in non-seminomatous germ cell tumors (NSGCT) are differently composed and less abundant. Previously, we have shown that the seminomatous cell line TCam-2 promotes T cell and monocyte activation in a coculture model, resulting in mutual interactions between both cell types. Here we set out to compare this feature of TCam-2 cells with the non-seminomatous cell line NTERA-2. Peripheral blood T cells or monocytes cocultured with NTERA-2 cells failed to secrete relevant amounts of pro-inflammatory cytokines, and significantly downregulated the expression of genes encoding activation markers and effector molecules. In contrast, immune cells cocultured with TCam-2 cells produced IL-2, IL-6 and TNFα, and strongly upregulated the expression of multiple pro-inflammatory genes. Furthermore, the expression of genes involved in proliferation, stemness and subtype specification remained unaltered in NTERA-2 cells during coculture with T cells or monocytes, indicating the absence of mutual interactions. Collectively, our findings uncover fundamental differences between SGCT and NSGCT in their capability to generate a pro-inflammatory TME, which possibly impacts the clinical features and prognosis of both TGCC subtypes.
睾丸生殖细胞癌（TGCC）可细分为几种亚型。精原性生殖细胞肿瘤（SGCT）的特征是免疫细胞密集浸润，构成促炎性肿瘤微环境（TME），而非精原性生殖细胞肿瘤（NSGCT）中的免疫细胞组成不同且数量较少。此前，我们已经表明，精原性细胞系TCam-2在共培养模型中可促进T细胞和单核细胞活化，导致两种细胞类型之间相互作用。在此，我们着手比较TCam-2细胞与非精原性细胞系NTERA-2的这一特征。与NTERA-2细胞共培养的外周血T细胞或单核细胞未能分泌相关量的促炎细胞因子，并且显著下调了编码活化标志物和效应分子的基因表达。相反，与TCam-2细胞共培养的免疫细胞产生白细胞介素-2（IL-2）、白细胞介素-6（IL-6）和肿瘤坏死因子α（TNFα），并强烈上调多个促炎基因的表达。此外，在与T细胞或单核细胞共培养期间，NTERA-2细胞中参与增殖、干性和亚型特异性的基因表达保持不变，表明不存在相互作用。总的来说，我们的研究结果揭示了SGCT和NSGCT在产生促炎性TME能力方面的根本差异，这可能会影响两种TGCC亚型的临床特征和预后。
