Locally advanced nasopharyngeal carcinoma (LA-NPC) is a relatively rare disease in the west but more common in East Asia and areas of the Middle East like Saudi Arabia. Despite the advances in radiation therapy techniques, some patients relapse after treatment. In the coming era of cancer immunotherapy, prognostic factors for LA-NPC need to be further defined using immune-relevant markers. Several markers are available; however, the most robust and accessible/affordable marker is not well-defined. Retrospectively, tumor-infiltrating lymphocytes (TIL), their subsets as well as tumoral PD-L1 expression were analyzed in tumor tissues from 63 LA-NPC patients treated with platinum-based concurrent chemo-radiotherapy (CCRT) in addition to 20 cases with metastatic (MET) disease. Immunostaining was done using a validated and fully automated system. Scoring was done by two independent pathologists and results were compared. There was no statistical difference between LA-NPC and MET disease in terms of CD3+, CD8+ TIL infiltration, or tumoral PD-L1 expression. In LA-NPC, low CD3+ TIL infiltration highly correlated with shorter disease-free survival (DFS, HR = 8.5, p = < 0.001) and overall survival (OS, HR = 13, p = 0.015) with substantial agreement between scoring pathologists. A similar correlation was found between low CD8+ TIL and survival. Correlation of total TIL was significant with DFS (HR = 4.0, p = 0.008), borderline with OS and the correlation was dependent on the scoring pathologist. Having histological WHO type I&II correlated significantly with shorter DFS (HR 4.03, p = 0.008) and low CD3+ TIL (p = 0.009). Subgroup analysis of LA-NPC that included undifferentiated type (WHO type III) cases only (n = 58), showed a strong correlation between low CD3+ TIL and shorter DFS (HR = 7.2, p = < 0.001) and OS (HR = 17.3, p = 0.008). PD-L1 was expressed in 72% of type III LA-NPC cases while lacking PD-L1 expression correlated with shorter OS (HR = 6.1, p = 0.031). Patients with a combination of low CD3+ TIL and lack of PD-L1 expression had the worst OS (p < 0.001). CD3+ TIL is promising as a robust and independent prognostic marker for DFS and OS of LA-NPC patients treated with platinum-based CCRT. We would suggest the use of CD3 + TIL as a stratifying factor for LA-NPC, which warrants further validation in prospective trials.

中文翻译：

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CD3 + T淋巴细胞浸润是晚期鼻咽癌的独立预后因素。

局部晚期鼻咽癌（LA-NPC）在西部是一种相对罕见的疾病，但在东亚和中东地区（如沙特阿拉伯）更为常见。尽管放射治疗技术有所进步，但仍有一些患者在治疗后复发。在即将到来的癌症免疫疗法时代，需要使用免疫相关标记物进一步确定LA-NPC的预后因素。有几种标记可用；但是，最健壮和可访问/负担得起的标记并没有明确定义。回顾性分析了63例接受铂金同步放疗（CCRT）的LA-NPC患者的肿瘤组织中的肿瘤浸润淋巴细胞（TIL），其子集以及肿瘤PD-L1的表达以及20例转移性（MET）疾病。免疫染色是使用经过验证的全自动系统完成的。由两名独立的病理学家进行评分并比较结果。LA-NPC和MET疾病在CD3 +，CD8 + TIL浸润或肿瘤PD-L1表达方面无统计学差异。在LA-NPC中，低CD3 + TIL浸润与较短的无病生存期（DFS，HR = 8.5，p = <0.001）和总体生存期（OS，HR = 13，p = 0.015）高度相关，在评分病理学家之间基本吻合。在低CD8 + TIL与生存之间发现了类似的相关性。总TIL与DFS的相关性很显着（HR = 4.0，p = 0.008），与OS的临界值相关，并且该相关性取决于评分病理学家。组织学上的I＆II型WHO与较短的DFS（HR 4.03，p = 0.008）和较低的CD3 + TIL（p = 0.009）密切相关。仅包括未分化型（WHO III型）病例（n = 58）的LA-NPC的亚组分析显示，低CD3 + TIL和较短的DFS（HR = 7.2，p = <0.001）和OS（HR = 17.3）之间有很强的相关性，p ＝ 0.008）。PD-L1在72％的III型LA-NPC病例中表达，而缺乏与OS较短相关的PD-L1表达（HR = 6.1，p = 0.031）。CD3 + TIL低而PD-L1表达不足的患者的OS最差（p <0.001）。CD3 + TIL有望成为接受铂类CCRT治疗的LA-NPC患者DFS和OS的可靠且独立的预后标志物。我们建议将CD3 + TIL用作LA-NPC的分层因素，这需要在前瞻性试验中进行进一步验证。001）和OS（HR = 17.3，p = 0.008）。PD-L1在72％的III型LA-NPC病例中表达，而缺乏与OS较短相关的PD-L1表达（HR = 6.1，p = 0.031）。CD3 + TIL低而PD-L1表达不足的患者的OS最差（p <0.001）。CD3 + TIL有望成为接受铂类CCRT治疗的LA-NPC患者DFS和OS的可靠且独立的预后标志物。我们建议将CD3 + TIL用作LA-NPC的分层因素，这需要在前瞻性试验中进行进一步验证。001）和OS（HR = 17.3，p = 0.008）。PD-L1在72％的III型LA-NPC病例中表达，而缺乏与OS较短相关的PD-L1表达（HR = 6.1，p = 0.031）。CD3 + TIL低而PD-L1表达不足的患者的OS最差（p <0.001）。CD3 + TIL有望成为接受铂类CCRT治疗的LA-NPC患者DFS和OS的可靠且独立的预后标志物。我们建议将CD3 + TIL用作LA-NPC的分层因素，这需要在前瞻性试验中进行进一步验证。CD3 + TIL有望成为接受铂类CCRT治疗的LA-NPC患者DFS和OS的可靠且独立的预后标志物。我们建议将CD3 + TIL用作LA-NPC的分层因素，这需要在前瞻性试验中进行进一步验证。CD3 + TIL有望成为接受铂类CCRT治疗的LA-NPC患者DFS和OS的可靠且独立的预后标志物。我们建议将CD3 + TIL用作LA-NPC的分层因素，这需要在前瞻性试验中进行进一步验证。