Background

Immune checkpoint blockade (ICB) is considered as a promising approach for cancer treatment. However, the potency of ICB therapy in yolk sac tumors (YSTs) has not been confirmed, and the comprehensive analysis of tumor immune microenvironment and the expression of PD-1/PD-L1 and CTLA4 were also not thoroughly evaluated.

Methods

Immunohistochemistry was performed in formalin-fixed, paraffin-embedded tumor specimens from 23 YSTs patients to detect the density and distribution of tumor-infiltrating T cells, tertiary lymphoid structures (TLSs), as well as the expression of PD-1/PD-L1 and CTLA4.

Results

Overall, more than half (61 %) of all patients exhibited an immune-desert phenotype based on CD3⁺ T cells. PD-1 expression was identified in five tumor samples (21.7 %), and PD-L1 expression exhibited a different positive rate in tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs) (39.1 % and 17.4 %). Noteworthily, the rate of positive CTLA4 expression in both TCs and TILs was markedly higher (69.6 % and 56.5 %) than those of PD-1 and PD-L1 expression. Furthermore, TLSs were observed in 21.74 % of all tissues, and samples with TLSs exhibited significantly higher densities of TILs and higher expression of immune checkpoint molecules, particularly PD-1/PD-L1. In addition, tumors located in testes also exhibited a higher density of TILs and higher expression of immune checkpoint molecules.

Conclusion

Generally a high frequency of CTLA4 expression was found, PD-1/PD-L1 expression, the immune-inflamed phenotype, and TLSs were low frequency in YSTs, however, YSTs in testes showed a higher density of TILs and higher expression of immune checkpoint molecules.

中文翻译：

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卵黄囊肿瘤中 PD-1/PD-L1 和 CTLA4 表达以及肿瘤浸润淋巴细胞的详细表征

背景

免疫检查点阻断（ICB）被认为是一种有前途的癌症治疗方法。然而，ICB治疗卵黄囊肿瘤（YSTs）的效力尚未得到证实，肿瘤免疫微环境以及PD-1/PD-L1和CTLA4表达的综合分析也没有得到彻底评估。

方法

对 23 例 YST 患者的福尔马林固定、石蜡包埋的肿瘤标本进行免疫组化，检测肿瘤浸润 T 细胞的密度和分布、三级淋巴结构（TLS）以及 PD-1/PD-L1 的表达。和CTLA4。

结果

^{总体而言，超过一半 (61%) 的所有患者表现出基于 CD3 +} T 细胞的免疫沙漠表型。在5个肿瘤样本中检测到PD-1表达（21.7%），PD-L1表达在肿瘤细胞（TC）和肿瘤浸润淋巴细胞（TIL）中表现出不同的阳性率（39.1%和17.4%）。值得注意的是，TCs和TILs中CTLA4的阳性表达率（69.6%和56.5%）显着高于PD-1和PD-L1表达率。此外，在 21.74% 的组织中观察到了 TLS，并且具有 TLS 的样本表现出显着更高的 TIL 密度和更高的免疫检查点分子表达，尤其是 PD-1/PD-L1。此外，位于睾丸的肿瘤还表现出较高的 TIL 密度和较高的免疫检查点分子表达。

结论

一般来说，YST 中 CTLA4 表达频率较高，PD-1/PD-L1 表达、免疫炎症表型和 TLS 频率较低，但睾丸 YST 中 TIL 密度较高，免疫检查点表达较高分子。