Liu Tingyu, Greenberg Max, Wentland Carissa, Sepe Brandon, Bowe Sarah, Diercks Gillian, Huynh Tiffany, Mino-Kenudson Mari, Schlegel Richard, Kodack David, Benes Cyril, Engelman Jeffrey, Hartnick Christopher
Novartis Institutes for Biomedical Research, 250 Massachusetts Ave, Cambridge, MA 02139, United States.
Massachusetts General Hospital Cancer Center, 55 Fruit St, Boston, MA 02114, United States.
Int J Pediatr Otorhinolaryngol. 2017 Apr;95:133-138. doi: 10.1016/j.ijporl.2017.02.022. Epub 2017 Feb 21.
Tumor immunotherapy have broadened therapeutic options for tumor treatment. The role of immune function in juvenile recurrent respiratory papillomatosis (JRRP) has not been investigated. Applying immunoblockade inhibitors as a novel disease treatment is unclear. Our study, for the first time, evaluates immune infiltration and immuno-suppressive molecule expression in JRRP. Our study provides insights in possibly treating this disease with tumor immunotherapies. We aimed to determine expression of programmed death-ligand 1 (PD-L1), a cancer escape protein, and presence of CD8+ T cell infiltration in tumor microenvironment.
Seven patients with JRRP (mean age: 7.43; age range 3-17) in this study routinely have their tumors surgical debulked at Massachusetts Eye and Ear Infirmary. Following surgery, samples were de-identified and sent to pathology where they were stained and analyzed.
Six out of seven patients expressed PD-L1 on tumor cells to various extents. Three patients showed concurrent PD-L1 expression on tumor cells and abundant CD8+ tumor infiltrating lymphocytes as well as PD-L1+ stromal lymphocytes, while PD-L1 expression on tumor cells were not associated with CD8+ tumor infiltrating T cells nor PD-L1+ stromal lymphocytes in the other three patients. HPV 6/11 and p16 was detected in all the patients. There appeared to be no correlation between either PD-L1 expression and CD8+ infiltration and clinical severity as measured by both the number of surgeries per year or Derkay score.
Despite a small cohort, the expression of p16 and HPV 6/11 in all of the patients confirms the tissues were HPV tumor cells. PD-L1 expression was detected in the vast majority of tumor samples, while inflammatory cell compartments showed a higher degree of variation. Expression of PD-L1 on tumor cells but not inflammatory cells raises the possibility of a tumor cell intrinsic manner of PD-L1 expression. In contrast, a group of patients showed PD-L1 positivity in both tumor and inflammatory cells along with abundant CD8+ tumor infiltrating lymphocytes, suggesting adoptive immune resistance in these tumors and potential benefits from tumor immunotherapy.
肿瘤免疫疗法拓宽了肿瘤治疗的选择。免疫功能在青少年复发性呼吸道乳头状瘤病（JRRP）中的作用尚未得到研究。应用免疫阻断抑制剂作为一种新型疾病治疗方法尚不清楚。我们的研究首次评估了JRRP中的免疫浸润和免疫抑制分子表达。我们的研究为用肿瘤免疫疗法治疗这种疾病提供了见解。我们旨在确定程序性死亡配体1（PD-L1）的表达，一种癌症逃逸蛋白，以及肿瘤微环境中CD8 + T细胞浸润的存在情况。
本研究中的7例JRRP患者（平均年龄：7.43岁；年龄范围3 - 17岁）通常在马萨诸塞州眼耳医院对其肿瘤进行手术减瘤。手术后，样本进行去识别处理并送至病理科，在那里进行染色和分析。
7例患者中有6例在肿瘤细胞上不同程度地表达PD-L1。3例患者肿瘤细胞上同时表达PD-L1，且有丰富的CD8 +肿瘤浸润淋巴细胞以及PD-L1 +基质淋巴细胞，而在另外3例患者中，肿瘤细胞上的PD-L1表达与CD8 +肿瘤浸润T细胞及PD-L1 +基质淋巴细胞均无关。所有患者均检测到HPV 6/11和p16。PD-L1表达与CD8 +浸润以及通过每年手术次数或Derkay评分衡量的临床严重程度之间似乎均无相关性。
尽管样本量较小，但所有患者中p16和HPV 6/11的表达证实这些组织为HPV肿瘤细胞。在绝大多数肿瘤样本中检测到PD-L1表达，而炎症细胞区室显示出更高程度的变异性。肿瘤细胞而非炎症细胞上PD-L1的表达增加了PD-L1以肿瘤细胞内在方式表达的可能性。相反，一组患者在肿瘤和炎症细胞中均显示PD-L1阳性，同时伴有丰富的CD8 +肿瘤浸润淋巴细胞，提示这些肿瘤存在过继性免疫抵抗以及肿瘤免疫疗法可能带来的益处。
