Chen Shuqing, Pyne Justin M, Liu Yulun, Abraham Youstina, Wen Zhuoyu, Palsgrove Doreen, Xiao Guanghua, Truelson John, Myers Larry, Tillman Brittny, Day Andrew, Gordin Eli, Stankova Lenka, Xie Yang, Sher David, Bishop Justin, Gao Jinming, Sumer Baran D
Department of Otolaryngology-Head & Neck Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Head Neck. 2025 Apr;47(4):1199-1208. doi: 10.1002/hed.28006. Epub 2024 Dec 16.
Lymph node count (LNC) from neck dissection has been associated with undernutrition and survival in head and neck squamous cell carcinoma (HNSCC). As local components of the immune system, cervical lymph nodes may reflect anti-tumor immune status. This study investigates the relationship between decreased LNC, formation of tertiary lymphoid structures (TLS), and primary tumor infiltration by lymphocytes in undernourished patients.
A matched-cohort study was conducted in a tertiary medical center, where neck dissection quality was standardized for a total of 384 subjects that were evaluated. Six head and neck cancer patients that underwent primary surgery including neck dissection with low LNC and BMI (low BMI < 23, low LNC ≤ 5.6 per neck level) were matched by stage, p16 status, and subsite to 16 patients with normal BMI and high LNC. Multiplexed immunohistochemistry was used to evaluate the tumor-infiltrating lymphocytes and the number and quality of TLS within primary tumors. Whole primary cancers underwent automated analysis and counting of leukocytes after multiplexed immunohistochemistry staining of tumor slides. A head and neck pathologist blindly scored the number and maturity of TLS. Descriptive statistics were used to analyze outcomes.
The patients with low BMI and low LNC had significantly fewer CD3 (p = 0.0136), CD8 (p = 0.0003), and CD20 (p = 0.0334) cells in their primary tumors compared to patients with normal BMI and LNC. The low BMI low LNC patients also had fewer mature TLS (0.83/tumor) in their primary cancers compared to patients with normal BMI and high LNC (5.4/tumor) and also had greater than fourfold lower mature TLS density (TLS per μm mean) (6.34 × 10 vs. 2.82 × 10), with significantly worsened survival relative to patients with low BMI and normal LNC and patients with normal BMI.
Low LNC predicts worsened survival only in low BMI HNSCC patients with non-HPV related tumors and in these patients is associated with markers of immunosuppression such as fewer tumor-infiltrating CD8+ T-cells, CD20+ cells, and fewer TLS in primary cancers compared to matched normal BMI patients with high LNC.
颈部清扫术中的淋巴结计数（LNC）与头颈部鳞状细胞癌（HNSCC）的营养不良和生存率相关。作为免疫系统的局部组成部分，颈部淋巴结可能反映抗肿瘤免疫状态。本研究调查了营养不良患者中LNC降低、三级淋巴结构（TLS）形成与原发性肿瘤淋巴细胞浸润之间的关系。
在一家三级医疗中心进行了一项匹配队列研究，对总共384名接受评估的受试者的颈部清扫质量进行了标准化。6名头颈部癌症患者接受了包括颈部清扫术在内的初次手术，其LNC和体重指数较低（低体重指数<23，低LNC≤每个颈部水平5.6），根据分期、p16状态和亚部位与16名体重指数正常且LNC高的患者进行匹配。采用多重免疫组织化学法评估原发性肿瘤内的肿瘤浸润淋巴细胞以及TLS的数量和质量。在对肿瘤切片进行多重免疫组织化学染色后，对整个原发性癌进行白细胞的自动分析和计数。一名头颈部病理学家对TLS的数量和成熟度进行盲法评分。采用描述性统计分析结果。
与体重指数和LNC正常的患者相比，体重指数低且LNC低的患者原发性肿瘤中的CD3（p = 0.0136）、CD8（p = 0.0003）和CD20（p = 0.0334）细胞明显减少。与体重指数正常且LNC高的患者（5.4/肿瘤）相比，体重指数低且LNC低的患者原发性癌中的成熟TLS也较少（0.83/肿瘤），并且成熟TLS密度（每μm平均值的TLS）降低超过四倍（6.34×10对2.82×10），相对于体重指数低且LNC正常的患者以及体重指数正常的患者，其生存率显著恶化。
低LNC仅在患有非HPV相关肿瘤的低体重指数HNSCC患者中预示生存率恶化，并且在这些患者中，与免疫抑制标志物相关，例如与匹配的体重指数正常且LNC高的患者相比，原发性癌中肿瘤浸润的CD8 + T细胞、CD20 +细胞较少，TLS也较少。
