Immunophenotypes Based on the Tumor Immune Microenvironment Allow for Unsupervised Penile Cancer Patient Stratification
Immunophenotypes Based on the Tumor Immune Microenvironment Allow for Unsupervised Penile Cancer Patient Stratification
复制标题
基于肿瘤免疫微环境的免疫表型允许对阴茎癌患者进行无人监督的分层。
DOI：
10.3390/cancers12071796
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发表时间：
2020-07-01
期刊：
影响因子：
5.2
通讯作者：
Cao, Yun
中科院分区：
文献类型：
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作者：
Chu, Chengbiao;Yao, Kai;Cao, Yun
肿瘤免疫微环境（TIME）在阴茎鳞状细胞癌（peSCC）的发病机制中起重要作用。在这里，通过整合免疫检查点的表达模式，确定了癌细胞中TIME的免疫表型。（程序性细胞死亡-1（PD-1）/程序性细胞死亡配体-1（PD-L1）、细胞毒性T淋巴细胞抗原4（CTLA-4）和Siglec-15）和肿瘤浸润淋巴细胞的组分，包括CD 8（+）或粒酶B+T细胞、FOXP 3（+）调节性T细胞、CD 68（+）或CD 206（+）巨噬细胞。颗粒酶B、FOXP 3、CD 68、CD 206、PD-1和CTLA-4的高密度与较好的疾病特异性生存期（DSS）相关。PD-L1肿瘤细胞弥漫性表达的患者比边缘表达或阴性表达的患者的预后差。基于某些免疫标志物，通过非监督聚类分析确定了四种免疫表型，它们与鳞状细胞癌的DSS和淋巴结转移（LNM）相关。免疫表型与高危型人乳头瘤病毒（hrHPV）感染无明显关系。然而，hrHPV阳性的peSCC表现出比hrHPV阴性肿瘤更高的基质颗粒酶B和肿瘤内PD-1密度（分别为p= 0.049和0.002）。结论：peSCC的免疫表型对预测淋巴结转移和预后具有重要价值，可为临床分层管理和免疫治疗干预提供依据。
The tumor immune microenvironment (TIME) plays an important role in penile squamous cell carcinoma (peSCC) pathogenesis. Here, the immunophenotype of the TIME in peSCC was determined by integrating the expression patterns of immune checkpoints (programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1), cytotoxic T lymphocyte antigen 4 (CTLA-4), and Siglec-15) and the components of tumor-infiltrating lymphocytes, including CD8(+)or Granzyme B+T cells, FOXP3(+)regulatory T cells, and CD68(+)or CD206(+)macrophages, in 178 patients. A high density of Granzyme B, FOXP3, CD68, CD206, PD-1, and CTLA-4 was associated with better disease-specific survival (DSS). The patients with diffuse PD-L1 tumor cell expression had worse prognoses than those with marginal or negative PD-L1 expression. Four immunophenotypes were identified by unsupervised clustering analysis, based on certain immune markers, which were associated with DSS and lymph node metastasis (LNM) in peSCC. There was no significant relationship between the immunophenotypes and high-risk human papillomavirus (hrHPV) infection. However, the hrHPV-positive peSCC exhibited a higher density of stromal Granzyme B and intratumoral PD-1 than the hrHPV-negative tumors (p= 0.049 and 0.002, respectively). In conclusion, the immunophenotypes of peSCC were of great value in predicting LNM and prognosis, and may provide support for clinical stratification management and immunotherapy intervention.