Ilie Marius, Falk Alexander T, Butori Catherine, Chamorey Emmanuel, Bonnetaud Christelle, Long Elodie, Lassalle Sandra, Zahaf Katia, Vénissac Nicolas, Mouroux Jérôme, Cohen Charlotte, Brambilla Elisabeth, Marquette Charles Hugo, Hofman Véronique, Hofman Paul
Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France.
Institute for Research on Cancer and Ageing, Nice (IRCAN), INSERM U1081/UMR CNRS 7284, Team 3, University of Nice Sophia Antipolis, Antoine Lacassagne Center, Nice, France.
Mod Pathol. 2016 Dec;29(12):1552-1564. doi: 10.1038/modpathol.2016.149. Epub 2016 Aug 26.
PD-1/PD-L1 inhibitors demonstrated durable clinical responses in patients with lung squamous cell carcinoma. However, the expression pattern of PD-L1 and the presence of CD8 and PD-1 tumor-infiltrating T cells in the basaloid variant of squamous cell carcinoma remain unknown. immunohistochemistry analysis of PD-L1 expression, with three recently validated monoclonal antibodies used in clinical trials (clones SP142, SP263, and 28-8), and detection of CD8 and PD-1 tumor-infiltrating T cells was performed on whole-tissue sections from 56 patients following surgery for basaloid squamous cell carcinoma. Data were correlated to clinicopathological parameters and outcome. Fair to poor concordance was observed between the SP142 vs SP263 clones, and SP142 vs 28-8 (κ range, 0.018-0.412), while the 28-8 and SP263 demonstrated a strong correlation in both the tumor cell and immune cell compartments (κ=0.883, and κ=0.721). Expression of PD-L1 correlated with a high content of CD8 and PD-1 tumor-infiltrating T cells when using SP142 (P=0.012; P=0.022), but not with SP263 or 28-8 (P=0.314; P=0.611). In the multivariate analysis, we found significantly better disease-free and overall survival rates for high PD-L1 expression with SP142, CD8 and PD-1 tumor-infiltrating T cells (P=0.003; P=0.007). No significant prognosis value was observed for SP263 and 28-8 clones, except a correlation between improved overall survival and SP263 in the univariate analysis (P=0.039), not confirmed in the multivariate model. In conclusion, we report that the expression of PD-L1 and the content of CD8 and PD-1 tumor-infiltrating T cells is an independent indicator of better outcome in basaloid squamous cell carcinoma patients, although the observed effect is dependent on the PD-L1 immunohistochemistry assay.
PD-1/PD-L1抑制剂在肺鳞状细胞癌患者中显示出持久的临床反应。然而,在鳞状细胞癌的基底样变体中,PD-L1的表达模式以及CD8和PD-1肿瘤浸润性T细胞的存在情况仍不清楚。我们使用三种最近在临床试验中得到验证的单克隆抗体(克隆号SP142、SP263和28-8)对56例基底样鳞状细胞癌患者术后的全组织切片进行了PD-L1表达的免疫组织化学分析,并检测了CD8和PD-1肿瘤浸润性T细胞。将数据与临床病理参数和预后相关联。观察到SP142与SP263克隆之间以及SP142与28-8之间的一致性一般至较差(κ范围为0.018 - 0.412),而28-8和SP263在肿瘤细胞和免疫细胞区室中均表现出强相关性(κ = 0.883和κ = 0.721)。当使用SP142时,PD-L1的表达与高含量的CD8和PD-1肿瘤浸润性T细胞相关(P = 0.012;P = 0.022),但与SP263或28-8无关(P = 0.314;P = 0.611)。在多变量分析中,我们发现对于SP142、CD8和PD-1肿瘤浸润性T细胞高表达的患者,无病生存率和总生存率显著更好(P = 0.003;P = 0.007)。除了在单变量分析中总生存率改善与SP263之间存在相关性(P = 0.039),但在多变量模型中未得到证实外,未观察到SP263和28-8克隆具有显著的预后价值。总之,我们报告PD-L1的表达以及CD8和PD-1肿瘤浸润性T细胞的含量是基底样鳞状细胞癌患者预后较好的独立指标,尽管观察到的效果取决于PD-L1免疫组织化学检测方法。