Department of Radiation Oncology at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Department of Medical Oncology at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
BMC Cancer. 2020 Mar 21;20(1):240. doi: 10.1186/s12885-020-06757-w.
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.
局部晚期鼻咽癌（LA-NPC）在西方较为少见，但在东亚和沙特阿拉伯等中东地区较为常见。尽管放射治疗技术取得了进步，但一些患者在治疗后仍会复发。在癌症免疫治疗的时代，需要使用免疫相关标志物进一步定义 LA-NPC 的预后因素。有几种标志物可用；然而，最健壮和可及/负担得起的标志物尚未得到很好的定义。
回顾性分析了 63 例接受铂类同期放化疗（CCRT）治疗的 LA-NPC 患者和 20 例转移性（MET）疾病患者的肿瘤组织中肿瘤浸润淋巴细胞（TIL）及其亚群以及肿瘤 PD-L1 表达。使用经过验证和完全自动化的系统进行免疫染色。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 浸润与无病生存期（DFS，HR=8.5，p<0.001）和总生存期（OS，HR=13，p=0.015）显著相关，两位评分病理学家之间具有显著一致性。低 CD8+TIL 与生存也存在类似的相关性。总 TIL 的相关性与 DFS（HR=4.0，p=0.008）显著相关，与 OS 相关，但与 OS 相关的相关性取决于评分病理学家。具有组织学 WHO 类型 I&II 与较短的 DFS（HR 4.03，p=0.008）和低 CD3+TIL（p=0.009）显著相关。仅包括未分化型（WHO 类型 III）病例的 LA-NPC 亚组分析（n=58）显示，低 CD3+TIL 与较短的 DFS（HR=7.2，p<0.001）和 OS（HR=17.3，p=0.008）之间存在强烈相关性。72%的 III 型 LA-NPC 病例表达 PD-L1，而缺乏 PD-L1 表达与较短的 OS 相关（HR=6.1，p=0.031）。同时存在低 CD3+TIL 和缺乏 PD-L1 表达的患者 OS 最差（p<0.001）。
CD3+TIL 是一种有前途的、健壮的独立预后标志物，可预测接受铂类 CCRT 治疗的 LA-NPC 患者的 DFS 和 OS。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一步验证。
