Department of Otorhinolaryngology, Head and Neck Surgery, University of Ulm, Ulm, Germany.
CRUK and NIHR Experimental Cancer Medicine Center and School of Cancer Sciences, Faculty of Medicine, H, Southampton, United Kingdom.
Clin Cancer Res. 2024 Jan 5;30(1):224-234. doi: 10.1158/1078-0432.CCR-23-0445.
High numbers of tumor-infiltrating lymphocytes (TIL) are linked to better survival in patients with cancer. Tissue-resident memory T cells (TRM; CD8+CD103+) are recognized as a key player of anticancer immune response. To assess TRM cells in primary, metastatic, and recurrent head and neck squamous cell carcinoma (HNSCC), we developed a tissue microarray (TMA) and used multiplex IHC (MxIHC).
Samples from primary tumors of 379 HNSCC cases treated at Southampton Hospitals between 2000 and 2016 were collected and analyzed. Of these, 105 cases had lymph node metastases and 82 recurrences. A TMA was generated with triplicate cores for each sample. MxIHC with a stain-and-strip approach was performed using CD8, CD103, and TIM3. Scanned slides were analyzed (digital image analysis) and quality checked (QC).
After QC, 194 primary tumors, 76 lymph node metastases, and 65 recurrences were evaluable. Alcohol consumption was statistically significantly correlated with a reduction of TRM cells in primary tumors (nondrinker vs. heavy drinker: P = 0.0036). The known survival benefit of TRM cell infiltration in primary tumors was not found for lymph node metastasis. In recurrences, a high TRM cell number led to a favorable outcome after 12 months. The checkpoint molecule TIM3, was expressed significantly higher on TRM and non-TRM cells in the lymph node compared with primary tumors (P < 0.0001), which was also seen in recurrences (P = 0.0134 and P = 0.0007, respectively).
We confirm the prognostic impact of TIL in primary tumors and in recurrences. TRM cell density in lymph node metastases was not linked to outcome. The role of TIM3, as a therapeutic target remains to be defined.
大量浸润肿瘤的淋巴细胞（TIL）与癌症患者的生存改善相关。组织驻留记忆 T 细胞（TRM；CD8+CD103+）被认为是抗肿瘤免疫反应的关键参与者。为了评估原发性、转移性和复发性头颈部鳞状细胞癌（HNSCC）中的 TRM 细胞，我们开发了组织微阵列（TMA）并使用了多重免疫组化（MxIHC）。
收集并分析了 2000 年至 2016 年间在南安普顿医院治疗的 379 例 HNSCC 患者的原发性肿瘤样本。其中 105 例有淋巴结转移，82 例复发。每个样本生成了 3 个重复核心的 TMA。使用染色和剥离方法进行了 MxIHC，并用 CD8、CD103 和 TIM3 进行染色。扫描载玻片进行了分析（数字图像分析）和质量检查（QC）。
经过 QC，可评估的有 194 例原发性肿瘤、76 例淋巴结转移和 65 例复发。酒精摄入量与原发性肿瘤中 TRM 细胞减少呈统计学显著相关（非饮酒者与重度饮酒者：P = 0.0036）。原发性肿瘤中 TRM 细胞浸润的已知生存获益并未在淋巴结转移中发现。在复发中，TRM 细胞数量高与 12 个月后的良好结果相关。在淋巴结中，与原发性肿瘤相比，检查点分子 TIM3 在 TRM 和非 TRM 细胞上的表达显著更高（P < 0.0001），在复发中也观察到了这种情况（P = 0.0134 和 P = 0.0007）。
我们证实了 TIL 在原发性肿瘤和复发中的预后影响。淋巴结转移中 TRM 细胞密度与结局无关。TIM3 作为治疗靶点的作用仍有待确定。
