Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Jiangsu, China.
Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Jiangnan University, Jiangsu, China.
J Oral Pathol Med. 2018 Apr;47(4):359-367. doi: 10.1111/jop.12698. Epub 2018 Mar 12.
Tumor-infiltrating lymphocytes (TILs) are regarded as adaptive immune response of the host to cancer cells and valuable prognostic factors. Here, we sought to characterize the densities and locations of CD3 and CD8 TILs in primary oral squamous cell carcinoma (OSCC) samples and assess their clinicopathological and prognostic significance.
A total number of 169 OSCC samples from 2 independent patient cohorts (Nanjing cohort, 93 cases; Wuxi cohort, 76 cases) were retrospectively collected. The numbers of CD3 and CD8 TILs at tumor center (CT) and invasive margin (IM) of OSCC were identified by immunohistochemistry and calculated. The optimal cutoff values for CD3 and CD8 TILs to stratify patients were determined by X-tile software in Nanjing cohort and further utilized in Wuxi cohort. The associations between CD3 /CD8 TILs and clinicopathological parameters or patient survival were assessed. The prognostic values of CD3 / CD8 TILs were evaluated by Cox regression analyses.
CD3 and CD8 TILs were identified at both CT and IM and enriched at IM. High density of CD3 TILs at IM (CD3 IM) was significantly associated with increased overall and disease-specific survival (P < .05). High density of CD8 TILs at CT (CD8 CT) was significantly associated with increased overall but not disease-specific survival. Moreover, CD3 IM and CD8 CT were identified as independent prognostic factors for patient survival.
Our findings provide further evidence to support the prognostic values of CD3 and CD8 TILs for OSCC, suggesting that TIL subsets might be viable biomarkers and therapeutic targets with translational significance.
肿瘤浸润淋巴细胞（TILs）被认为是宿主对癌细胞的适应性免疫反应，也是有价值的预后因素。在这里，我们试图描述原发性口腔鳞状细胞癌（OSCC）样本中 CD3 和 CD8 TIL 的密度和位置，并评估其临床病理和预后意义。
回顾性收集了来自 2 个独立患者队列（南京队列，93 例；无锡队列，76 例）的总共 169 例 OSCC 样本。通过免疫组织化学鉴定 OSCC 肿瘤中心（CT）和浸润边缘（IM）的 CD3 和 CD8 TIL 数量，并通过 X-tile 软件在南京队列中确定 CD3 和 CD8 TIL 分层患者的最佳截断值，并在无锡队列中进一步使用。评估 CD3/CD8 TIL 与临床病理参数或患者生存之间的关系。通过 Cox 回归分析评估 CD3/CD8 TIL 的预后价值。
在 CT 和 IM 均鉴定出 CD3 和 CD8 TIL，并在 IM 处富集。IM 处 CD3 TIL 密度高（CD3 IM）与总生存率和疾病特异性生存率增加显著相关（P<0.05）。CT 处 CD8 TIL 密度高（CD8 CT）与总生存率增加显著相关，但与疾病特异性生存率无关。此外，CD3 IM 和 CD8 CT 被确定为患者生存的独立预后因素。
我们的研究结果进一步支持 CD3 和 CD8 TIL 对 OSCC 的预后价值，表明 TIL 亚群可能是具有转化意义的可行生物标志物和治疗靶点。
