Background

Immune cell infiltration is heterogeneous but common in testicular germ cell tumors (TGCT) and pre-invasive germ cell neoplasia in situ (GCNIS). Tumor-infiltrating T cells including regulatory T (Treg) and follicular helper T (Tfh) cells are found in other cancer entities, but their contributions to TGCT are unknown.

Methods

Human testis specimens from independent patient cohorts were analyzed using immunohistochemistry, flow cytometry and single-cell RNA sequencing (scRNA-seq) with special emphasis on delineating T cell subtypes.

Results

Profound changes in immune cell composition within TGCT, shifting from macrophages in normal testes to T cells plus B and dendritic cells in TGCT, were documented. In most samples (96%), the CD4+ T cell frequency exceeded that of CD8+ cells, with decreasing numbers from central to peripheral tumor areas, and to tumor-free, contralateral testes. T cells including Treg and Tfh were most abundant in seminoma compared to mixed tumors and embryonal carcinoma.

Conclusion

Despite considerable heterogeneity between patients, T cell subtypes form a key part of the TGCT microenvironment. The novel finding of rare Treg and Tfh cells in human testis suggests their involvement in TGCT pathobiology, with implications for understanding tumor progression, to assess patients’ prognosis, and as putative targets for personalized immunotherapy.

中文翻译：

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睾丸生殖细胞肿瘤中的 T 细胞：稀有亚群的基本贡献的新证据

背景

免疫细胞浸润具有异质性，但常见于睾丸生殖细胞肿瘤（TGCT）和浸润前生殖细胞原位肿瘤（GCNIS）。在其他癌症实体中发现了肿瘤浸润 T 细胞，包括调节性 T (Treg) 和滤泡辅助 T (Tfh) 细胞，但它们对 TGCT 的贡献尚不清楚。

方法

使用免疫组织化学、流式细胞术和单细胞 RNA 测序 (scRNA-seq) 对来自独立患者队列的人类睾丸标本进行分析，特别强调描绘 T 细胞亚型。

结果

TGCT 内的免疫细胞组成发生了深刻的变化，从正常睾丸中的巨噬细胞转变为 TGCT 中的 T 细胞加 B 细胞和树突状细胞。在大多数样本 (96%) 中，CD4+ T 细胞频率超过 CD8+ 细胞，从中央肿瘤区域到外周肿瘤区域以及无肿瘤的对侧睾丸，数量逐渐减少。与混合肿瘤和胚胎癌相比，包括 Treg 和 Tfh 在内的 T 细胞在精原细胞瘤中最为丰富。

结论

尽管患者之间存在相当大的异质性，但 T 细胞亚型构成了 TGCT 微环境的关键部分。人类睾丸中罕见 Treg 和 Tfh 细胞的新发现表明它们参与 TGCT 病理学，对于了解肿瘤进展、评估患者预后以及作为个性化免疫治疗的推定靶点具有重要意义。