An Zhaohong, Zhang Xiwei, Wang Zhaoyang, Wusiman Dilinaer, Zhao Xiaohui, Li Lin, Guo Lei, Wei Minghui, Li Wenbin, An Changming
Department of Head and Neck Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Purdue Institute for Cancer Research, Purdue University, West Lafayette, IN 47906, USA.
Oral Oncol. 2025 Feb;161:107151. doi: 10.1016/j.oraloncology.2024.107151. Epub 2025 Jan 1.
Optimizing clinical decision-making in head and neck squamous cell carcinoma (HNSCC) is challenging due to the ambiguous understanding of the immune cell dynamics and immune checkpoints regulation in the disease after the administration of neoadjuvant immunotherapy (NIT).
HNSCC biopsy samples collected before and after the neoadjuvant treatment are classified into the pathologic response (PR) and the non-pathologic response (NPR) groups according to treatment responses and the expression of immune cells and checkpoints was labeled using multiplex immunohistochemistry (m-IHC).
The populations of CD4 T cells, CD8 T cells, regulatory T cells (Treg), PD-1, and PD-L1 were particularly higher in the PR group than the NPR group in pre-treatment tissues, with the p-values of log-transformed positive cell density <0.05. Almost all markers showed a lower expression in the PR patients after treatment, resulting lower post/pre-treatment ratios of positive cell densities in the PR patients relative to the NPR patients. Following treatment, TIM3 T cells and LAG3 T cells exhibited significantly diminished levels in the PR cohort relative to the NPR cohort, with post/pre-treatment expression ratios showing significant differences (P < 0.05). Tumor infiltration lymphocyte analysis revealed that the PR group exhibited a considerably higher average density of CD8 T cells infiltrating in the tumor marginal zone.
The presence of T cells demonstrated significant predictive capability for responses to neoadjuvant immunotherapy in HNSCC patients. Furthermore, TIM3 T cells and LAG3 T cells were found to be remarkably lower in the partial response (PR) cohort than in the non-partial response (NPR) cohort post-treatment. This research contributes critical understanding of the physiological changes occurring in immune cell responses.
由于对新辅助免疫治疗（NIT）后头颈部鳞状细胞癌（HNSCC）中免疫细胞动态和免疫检查点调节的理解不明确，优化该疾病的临床决策具有挑战性。
根据治疗反应，将新辅助治疗前后收集的HNSCC活检样本分为病理反应（PR）组和非病理反应（NPR）组，并使用多重免疫组织化学（m-IHC）标记免疫细胞和检查点的表达。
在治疗前组织中，PR组的CD4 T细胞、CD8 T细胞、调节性T细胞（Treg）、PD-1和PD-L1的数量明显高于NPR组，对数转换后的阳性细胞密度的p值<0.05。几乎所有标志物在治疗后的PR患者中表达较低，导致PR患者相对于NPR患者的阳性细胞密度治疗后/治疗前比值较低。治疗后，与NPR队列相比，PR队列中的TIM3 T细胞和LAG3 T细胞水平显著降低，治疗后/治疗前表达比值显示出显著差异（P<0.05）。肿瘤浸润淋巴细胞分析显示，PR组在肿瘤边缘区浸润的CD8 T细胞平均密度相当高。
T细胞的存在对HNSCC患者新辅助免疫治疗的反应具有显著的预测能力。此外，发现部分反应（PR）队列中的TIM3 T细胞和LAG3 T细胞在治疗后明显低于非部分反应（NPR）队列。本研究有助于深入了解免疫细胞反应中发生的生理变化。
