Department of Otolaryngology, Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto Universitario de Oncología del Principado de Asturias, University of Oviedo, 33011, Oviedo, Spain.
Ciber de Cáncer, CIBERONC, 28029, Madrid, Spain.
Cancer Immunol Immunother. 2020 Oct;69(10):2089-2100. doi: 10.1007/s00262-020-02604-w. Epub 2020 May 24.
The importance of immune tumor microenvironment in the prognosis of patients with head and neck squamous carcinomas (HNSCC) is increasingly recognized. We analyzed the prognostic relevance of PD-L1 and PD-1 expressions in relation to the infiltration by CD8 and FOXP3 tumor-infiltrating lymphocytes (TILs).
Samples from 372 surgically treated HPV-negative HNSCC patients were evaluated by immunohistochemistry for PD-L1 expression [both tumor proportion score (TPS) and combined proportion score (CPS)], PD-1 expression in immune cells, and density of infiltrating CD8 and FOXP3 TILs. PD-L1 expression and CD8 TIL density were combined to establish the type of tumor microenvironment.
29.5% cases exhibited PD-L1 TPS positivity (≥ 1%), whereas PD-L1 CPS positivity (≥ 1%) was observed in 40% cases. 47.5% cases showed positive PD-1 expression (≥ 1%). PD-L1 and PD-1 positivity correlated with a high density of both CD8 and FOXP3 TILs. In univariate analysis, PD-L1 TPS positivity (P = 0.026), PD-L1 CPS positivity (P = 0.004), high density of CD8 TIL (P = 0.001), and high density of FOXP3 TIL (P = 0.004) were associated with a better disease-specific survival (DSS). However, in multivariate analysis, only high density of CD8 TIL was associated with a better DSS (P = 0.002). The type of tumor microenvironment correlated with DSS (P = .008), with the better DSS observed in cases with type I (PD-L1 CPS positivity and high density of CD8 TIL).
High infiltration by CD8 TIL is associated with better survival outcomes. Positive PD-L1 expression correlates with a high infiltration by TILs, explaining its association with better prognosis.
免疫肿瘤微环境对头颈部鳞状细胞癌（HNSCC）患者的预后具有重要意义。我们分析了 PD-L1 和 PD-1 表达与 CD8 和 FOXP3 肿瘤浸润淋巴细胞（TIL）浸润的相关性及其预后意义。
采用免疫组织化学方法检测 372 例手术治疗的 HPV 阴性 HNSCC 患者的 PD-L1 表达（肿瘤比例评分[TPS]和联合比例评分[CPS]）、免疫细胞中的 PD-1 表达以及浸润性 CD8 和 FOXP3 TIL 的密度。将 PD-L1 表达和 CD8 TIL 密度结合起来建立肿瘤微环境的类型。
29.5%的病例表现出 PD-L1 TPS 阳性（≥1%），而 40%的病例 PD-L1 CPS 阳性（≥1%）。47.5%的病例表现出 PD-1 阳性表达（≥1%）。PD-L1 和 PD-1 的阳性与 CD8 和 FOXP3 TIL 的高密度均相关。单因素分析显示，PD-L1 TPS 阳性（P=0.026）、PD-L1 CPS 阳性（P=0.004）、CD8 TIL 高密度（P=0.001）和 FOXP3 TIL 高密度（P=0.004）与疾病特异性生存（DSS）相关。然而，多因素分析显示，只有 CD8 TIL 高密度与更好的 DSS 相关（P=0.002）。肿瘤微环境的类型与 DSS 相关（P=0.008），其中 PD-L1 CPS 阳性和 CD8 TIL 高密度的病例 DSS 更好。
CD8 TIL 的高浸润与生存结局改善相关。阳性 PD-L1 表达与 TIL 浸润相关，解释了其与更好预后的相关性。
