Sznurkowski Jacek J, Żawrocki Anton, Sznurkowska Katarzyna, Pęksa Rafał, Biernat Wojciech
Department of Oncological Surgery, The Medical University, Gdańsk, Poland.
Department of Pathology, The Medical University, Gdańsk, Poland.
Oncotarget. 2017 Sep 15;8(52):89903-89912. doi: 10.18632/oncotarget.20911. eCollection 2017 Oct 27.
Anti-immune programmed death-ligand 1 (PD-L1) pathway is used by the tumor to overcome immune system and serves as immunotherapy target in various malignancies.
To investigate the expression of PD-L1 in vulvar squamous cell carcinoma (vSCC) and to assess it's clinicopathological and prognostic significance.
Immunohistochemical PD-L1 expression was evaluated in 84 vSCCs with previously defined status of p16 and DNA-HPV, infiltration of immune cells: CD8+, CD4+, FOXP3+, CD56+, CD68+, and GZB+ cells. PD-L1 positivity was defined as ≥5% of PD-L1-positive cells. Survival analyses included the Kaplan-Meier method, log-rank test and Cox proportional hazards model.
PD-L1 expression was detected on cancer and peritumoral immune cells. PD-L1-positivity of cancer nests (27/84, 32.1%) was correlated with higher infiltration of CD4+ (p=0.037), CD8+ (p=0.02), FOXP3+ (p=0.007), CD68+ (p=0.021) cells, while PD-L1 positivity of peritumoral immune cells (51/84, 60.7%) was correlated with higher infiltration of intraepithelial FOXP3+ cells only (p=0.037).PD-L1-positivity of cancer cells but not immune cells, was more frequently observed in p16-negative tumors (p=0.004). High-risk HPV-status did not correlate with the PD-L1 status of cancer and immune cells (p=1.000) and (p=1.000) respectively). Median follow up was 89.20 months (range 1.7-189.5). PD-L1 positivity of peritumoral immune cells was found to be an independent favorable prognostic factor for OS. Conclusion: This study highlights the importance of comprehensive PD-L1 assessment in both cancer and immune cells. PD-L1 expression on peritumoral immune cells seems to be an additional prognostic factor in vSCC patients and may influence the results by anti-PD-L1 treatment.
肿瘤利用抗免疫程序性死亡配体1(PD-L1)途径来克服免疫系统,并且在各种恶性肿瘤中作为免疫治疗靶点。
研究PD-L1在外阴鳞状细胞癌(vSCC)中的表达,并评估其临床病理及预后意义。
采用免疫组化法评估84例vSCC中PD-L1的表达,同时评估其p16和DNA-HPV的既往状态、免疫细胞浸润情况:CD8+、CD4+、FOXP3+、CD56+、CD68+和GZB+细胞。PD-L1阳性定义为PD-L1阳性细胞≥5%。生存分析包括Kaplan-Meier法、对数秩检验和Cox比例风险模型。
在癌组织和瘤周免疫细胞中均检测到PD-L1表达。癌巢的PD-L1阳性(27/84,32.1%)与CD4+(p=0.037)、CD8+(p=0.02)、FOXP3+(p=0.007)、CD68+(p=0.021)细胞的较高浸润相关,而瘤周免疫细胞的PD-L1阳性(51/84,60.7%)仅与上皮内FOXP3+细胞的较高浸润相关(p=0.037)。在p16阴性肿瘤中更频繁地观察到癌细胞而非免疫细胞的PD-L1阳性(p=0.004)。高危HPV状态分别与癌组织和免疫细胞的PD-L1状态无关(p=1.000)和(p=1.000)。中位随访时间为89.20个月(范围1.7-189.5)。发现瘤周免疫细胞的PD-L1阳性是总生存期的独立有利预后因素。结论:本研究强调了在癌组织和免疫细胞中全面评估PD-L1的重要性。瘤周免疫细胞上的PD-L1表达似乎是vSCC患者的另一个预后因素,并且可能影响抗PD-L1治疗的结果。