Kandl Thomas J, Sagiv Oded, Curry Jonathan L, Ning Jing, Ma Junsheng, Hudgens Courtney W, Van Arnam John, Wargo Jennifer A, Esmaeli Bita, Tetzlaff Michael T
Orbital Oncology and Ophthalmic Plastic Surgery, Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Department of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Oncoimmunology. 2018 Jul 26;7(9):e1475874. doi: 10.1080/2162402X.2018.1475874. eCollection 2018.
Ocular adnexal sebaceous carcinoma (OASC) is an aggressive malignancy that frequently recurs locally and metastasizes. Surgical extirpation may produce significant aesthetic morbidity, and effective systemic therapies for locally advanced or metastatic disease are largely ineffective. Immune checkpoint inhibitors have shown efficacy in the management of several solid tumors where tumor cell PD-L1 expression correlates with improved response. To determine whether OASC might be amenable to immune checkpoint blockade, we performed comprehensive immune profiling for CD3, CD8, PD-1, FOXP3, and PD-L1 in 24 patients with primary OASC. The composition, distribution and density of the tumor associated immune infiltrate were quantified by automated image analysis and correlated with measures of clinical outcome. Tumor cells in 12 OASCs (50%) expressed PD-L1. Higher densities of CD3+ (p = 0.01), CD8+ (p = 0.006), and PD-1+ (p = 0.024) tumor-associated T cells were associated with higher T category (≥T3a per the 7th edition of the American Joint Committee on Cancer staging manual). Higher tumor cell expression of PD-L1 correlated with higher density of PD-1+ tumor-associated T cells (p = 0.021). Since a CD3+ CD8+ PD-1 + T-cell infiltrate represents a "suppressed T-cell phenotype" apparently permissive toward OASC progression, our findings provide a mechanistic rationale for the effective application of immune checkpoint blockade in OASC to abrogate PD-1/PD-L1 interaction and effectively unleash the immune infiltrate to treat higher-stage tumors.
眼附属器皮脂腺癌（OASC）是一种侵袭性恶性肿瘤，常发生局部复发和转移。手术切除可能会导致明显的美学损伤，而针对局部晚期或转移性疾病的有效全身治疗大多无效。免疫检查点抑制剂已在几种实体瘤的治疗中显示出疗效，其中肿瘤细胞PD-L1表达与更好的反应相关。为了确定OASC是否适合免疫检查点阻断治疗，我们对24例原发性OASC患者的CD3、CD8、PD-1、FOXP3和PD-L1进行了全面的免疫分析。通过自动图像分析对肿瘤相关免疫浸润的组成、分布和密度进行定量，并与临床结果指标相关联。12例OASC（50%）的肿瘤细胞表达PD-L1。较高密度的CD3+（p = 0.01）、CD8+（p = 0.006）和PD-1+（p = 0.024）肿瘤相关T细胞与更高的T分期（根据美国癌症联合委员会第7版癌症分期手册≥T3a）相关。肿瘤细胞更高的PD-L1表达与更高密度的PD-1+肿瘤相关T细胞相关（p = 0.021）。由于CD3+ CD8+ PD-1 + T细胞浸润代表一种“抑制性T细胞表型”，显然有利于OASC进展，我们的研究结果为在OASC中有效应用免疫检查点阻断以消除PD-1/PD-L1相互作用并有效释放免疫浸润以治疗更高分期肿瘤提供了机制依据。
