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Abstract：
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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
背景：免疫细胞浸润是异质性的，但常见于睾丸生殖细胞肿瘤（TGCT）和侵袭前生殖细胞原位瘤（GCNIS）。在其他癌症实体中发现了肿瘤浸润性T细胞，包括调节性T（Treg）和滤泡辅助性T（Tfh）细胞。但他们对TGCT的贡献是未知的。
方法：使用免疫组织化学分析来自独立患者队列的人睾丸标本，流式细胞术和单细胞RNA测序（scRNA-seq），特别强调描绘T细胞亚型。
结果：TGCT内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移到TGCT中的T细胞加B和树突状细胞，被记录在案。在大多数样本(96%)中，CD4+T细胞的频率超过了CD8+细胞,随着从中央到周围肿瘤区域的数量减少，和无肿瘤，对侧睾丸。与混合肿瘤和胚胎癌相比，包括Treg和Tfh的T细胞在精原细胞瘤中最丰富。
结论：尽管患者之间存在相当大的异质性，T细胞亚型构成TGCT微环境的关键部分。人类睾丸中罕见的Treg和Tfh细胞的新发现表明它们参与了TGCT病理学，对理解肿瘤进展有意义，为了评估患者的预后，并作为个性化免疫疗法的推定靶标。
方法：使用免疫组织化学分析来自独立患者队列的人睾丸标本，流式细胞术和单细胞RNA测序（scRNA-seq），特别强调描绘T细胞亚型。
结果：TGCT内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移到TGCT中的T细胞加B和树突状细胞，被记录在案。在大多数样本(96%)中，CD4+T细胞的频率超过了CD8+细胞,随着从中央到周围肿瘤区域的数量减少，和无肿瘤，对侧睾丸。与混合肿瘤和胚胎癌相比，包括Treg和Tfh的T细胞在精原细胞瘤中最丰富。
结论：尽管患者之间存在相当大的异质性，T细胞亚型构成TGCT微环境的关键部分。人类睾丸中罕见的Treg和Tfh细胞的新发现表明它们参与了TGCT病理学，对理解肿瘤进展有意义，为了评估患者的预后，并作为个性化免疫疗法的推定靶标。
