Outh-Gauer Sophie, Le Tourneau Christophe, Broudin Chloé, Scotte Florian, Roussel Hélène, Hans Stéphane, Mandavit Marion, Tartour Eric, Badoual Cécile
Service d'anatomie pathologique, hôpital européen Georges-Pompidou, AP-HP, 20, rue Leblanc, 75015 Paris, France.
Département d'oncologie médicale, institut Curie, 75005 Paris, France; Unité Inserm U900, 75005 Paris, France.
Ann Pathol. 2017 Feb;37(1):79-89. doi: 10.1016/j.annpat.2016.12.013. Epub 2017 Jan 19.
Head and neck (HN) carcinomas (mostly represented by squamous cell carcinomas [SCC]) still have a poor prognosis, which could be dramatically improved with immunotherapy. Tumor's microenvironment changes, caused by many endogenous or exogenous events, can correlate with prognosis and therapeutic response. Here, we review recent data regarding HNSCC, nasopharyngeal carcinomas (NPC) and salivary gland malignant tumors, all three being potential target of immunotherapies. About half of HNSCC exhibit PD-L1 expression, this expression being upregulated in HPV-positive tumors. In recent clinical trials, a better therapeutic response to anti-PD-1 has been obtained in patients with higher PD-L1 expression. Food and Drug Administration (FDA) approved the use of these therapeutics without the screening of patients regarding PD-L1 status. Activation status, density and localisation of TIL as well as PD-L2, γ-interferon, inflammatory cytokines, epithelial-mesenchymal transition phenotype and mutational burden may all be potential therapeutic response markers. In Epstein-Barr Virus (EBV)-induced nasopharyngeal non-keratinizing cancer, PD-L1 is over-expressed compared to EBV negative-tumors. A 22 % response rate has been observed under anti-PD-1 treatment, among PD-L1-positive HNSCC patients. There is little data regarding microenvironment of salivary gland cancer. PD-L1 shows great heterogeneity in localisation, when expressed. A 11 % response rate has been obtained under anti-PD-1 treatment among PD-L1-positive NPC patients. A better understanding of immune checkpoint regulation processes needs to be achieved to allow patients with HN carcinomas to benefit from these promising immunotherapies.
头颈部(HN)癌(主要为鳞状细胞癌[SCC])的预后仍然很差,而免疫疗法可显著改善其预后。由许多内源性或外源性事件引起的肿瘤微环境变化可能与预后和治疗反应相关。在此,我们综述了有关头颈部鳞状细胞癌(HNSCC)、鼻咽癌(NPC)和涎腺恶性肿瘤的最新数据,这三种肿瘤均为免疫疗法的潜在靶点。约一半的HNSCC表现出程序性死亡受体配体1(PD-L1)表达,这种表达在人乳头瘤病毒(HPV)阳性肿瘤中上调。在最近的临床试验中,PD-L1表达较高的患者对抗程序性死亡蛋白1(anti-PD-1)治疗有更好的反应。美国食品药品监督管理局(FDA)批准了这些疗法的使用,无需对患者进行PD-L1状态筛查。肿瘤浸润淋巴细胞(TIL)的激活状态、密度和定位以及PD-L2、γ干扰素、炎性细胞因子、上皮-间质转化表型和突变负荷都可能是潜在的治疗反应标志物。在爱泼斯坦-巴尔病毒(EBV)诱导的鼻咽非角化癌中,与EBV阴性肿瘤相比,PD-L1过度表达。在PD-L1阳性的HNSCC患者中,抗PD-1治疗的有效率为22%。关于涎腺癌微环境的数据很少。PD-L1表达时,其定位表现出很大的异质性。在PD-L1阳性的NPC患者中,抗PD-1治疗的有效率为11%。需要更好地了解免疫检查点调节过程,以使HN癌患者从这些有前景的免疫疗法中获益。