Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, Robert-Koch-Str. 3, 79106, Freiburg, Germany.
German Cancer Research Center (dkfz), German Cancer Consortium (DKTK) Partner Site Freiburg, Heidelberg, Germany.
Radiat Oncol. 2022 Nov 14;17(1):181. doi: 10.1186/s13014-022-02153-9.
Tumor-infiltrating lymphocytes (TILs) are associated with locoregional control (LRC) in head-and-neck squamous cell carcinoma (HNSCC) patients undergoing (chemo)radiotherapy. As immunosenescence results in reduced immune activity, the role of TILs in elderly HNSCC patients may differ compared to younger patients, providing a rationale to study the prognostic role of TILs and immune checkpoints (ICs) in this population.
Sixty-three HNSCC patients aged ≥ 65 years undergoing definitive (chemo)radiotherapy between 2010 and 2019 with sufficient material from pre-treatment biopsies were included in the analysis. Immunohistochemical stainings of CD3, CD4, CD8, PD-L1, TIM3, LAG3, TIGIT and CD96, and of osteopontin as an immunosenescence-associated protein were performed. Overall survival (OS) and progression-free survival (PFS) were determined using the Kaplan-Meier method, and Fine-Gray's models were used for locoregional failure (LRF) analyses.
While there was no correlation between patient age and IC expression, osteopontin levels correlated with increasing age (r = 0.322, p < 0.05). Two-year OS, PFS, and LRC were 44%, 34%, and 71%, respectively. Increased LAG3 expression, both intraepithelial (SHR = 0.33, p < 0.05) and stromal (SHR = 0.38, p < 0.05), and elevated stromal TIM3 expression (SHR = 0.32, p < 0.05) corresponded with reduced LRFs. Absent tumoral PD-L1 expression (TPS = 0%) was associated with more LRFs (SHR = 0.28, p < 0.05). There was a trend towards improved LRF rates in elderly patients with increased intraepithelial CD3 + (SHR = 0.52, p = 0.07) and CD8 + (SHR = 0.52, p = 0.09) TIL levels.
LAG3, TIM3 and TPS are promising biomarkers in elderly HNSCC patients receiving (chemo)radiotherapy. Considering the frequency of non-cancer related deaths in this population, the prognostic value of these biomarkers primarily relates to LRC.
肿瘤浸润淋巴细胞（TILs）与头颈部鳞状细胞癌（HNSCC）患者接受放化疗后的局部区域控制（LRC）相关。由于免疫衰老导致免疫活性降低，TILs 在老年 HNSCC 患者中的作用可能与年轻患者不同，这为研究 TILs 和免疫检查点（ICs）在该人群中的预后作用提供了依据。
纳入 2010 年至 2019 年期间接受根治性（放化疗）的 63 例年龄≥65 岁的 HNSCC 患者，这些患者在治疗前的活检中有足够的样本。进行 CD3、CD4、CD8、PD-L1、TIM3、LAG3、TIGIT 和 CD96 的免疫组化染色，以及作为免疫衰老相关蛋白的骨桥蛋白染色。使用 Kaplan-Meier 方法确定总生存期（OS）和无进展生存期（PFS），使用 Fine-Gray 模型进行局部区域失败（LRF）分析。
虽然患者年龄与 IC 表达之间没有相关性，但骨桥蛋白水平与年龄的增加呈正相关（r=0.322，p<0.05）。两年的 OS、PFS 和 LRC 分别为 44%、34%和 71%。上皮内（SHR=0.33，p<0.05）和基质中（SHR=0.38，p<0.05）LAG3 表达增加以及基质中 TIM3 表达升高（SHR=0.32，p<0.05）与 LRF 减少相关。肿瘤 PD-L1 表达缺失（TPS=0%）与更多的 LRF 相关（SHR=0.28，p<0.05）。在接受放化疗的老年患者中，上皮内 CD3+（SHR=0.52，p=0.07）和 CD8+（SHR=0.52，p=0.09）TIL 水平增加与 LRF 率提高呈趋势。
LAG3、TIM3 和 TPS 是接受放化疗的老年 HNSCC 患者有前途的生物标志物。考虑到该人群中与癌症无关的死亡频率，这些生物标志物的预后价值主要与 LRC 相关。
