Parikh Anuraag S, Li Yize, Mazul Angela, Yu Victoria X, Thorstad Wade, Rich Jason, Paniello Randal C, Caruana Salvatore M, Troob Scott H, Jackson Ryan S, Pipkorn Patrik, Zolkind Paul, Qi Zongtai, Adkins Douglas, Ding Li, Puram Sidharth V
Department of Otolaryngology-Head and Neck Surgery, Columbia University Irving Medical Center, New York, NY 10032, USA.
Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA.
Cancers (Basel). 2023 Oct 5;15(19):4855. doi: 10.3390/cancers15194855.
(1) Background: The role of rare immune cell subtypes in many solid tumors, chief among them head and neck squamous cell carcinoma (HNSCC), has not been well defined. The objective of this study was to assess the association between proportions of common and rare immune cell subtypes and survival outcomes in HNSCC. (2) Methods: In this cohort study, we utilized a deconvolution approach based on the CIBERSORT algorithm and the LM22 signature matrix to infer proportions of immune cell subtypes from 517 patients with untreated HPV-negative HNSCC from The Cancer Genome Atlas. We performed univariate and multivariable survival analysis, integrating immune cell proportions with clinical, pathologic, and genomic data. (3) Results: We reliably deconvolved 22 immune cell subtypes in most patients and found that the most common immune cell types were M0 macrophages, M2 macrophages, and memory resting CD4 T cells. In the multivariable analysis, we identified advanced N stage and the presence of γδ T cells as independently predictive of poorer survival. (4) Conclusions: We uncovered that γδ T cells in the tumor microenvironment were a negative predictor of survival among patients with untreated HNSCC. Our findings underscore the need to better understand the role of γδ T cells in HNSCC, including potential pro-tumorigenic mechanisms, and whether their presence may predict the need for alternative therapy approaches.
（1）背景：罕见免疫细胞亚群在许多实体瘤中的作用，其中主要是头颈部鳞状细胞癌（HNSCC），尚未得到明确界定。本研究的目的是评估常见和罕见免疫细胞亚群比例与HNSCC生存结果之间的关联。（2）方法：在这项队列研究中，我们利用基于CIBERSORT算法和LM22特征矩阵的反卷积方法，从癌症基因组图谱中517例未经治疗的HPV阴性HNSCC患者中推断免疫细胞亚群的比例。我们进行了单变量和多变量生存分析，将免疫细胞比例与临床、病理和基因组数据相结合。（3）结果：我们在大多数患者中可靠地反卷积出22种免疫细胞亚群，发现最常见的免疫细胞类型是M0巨噬细胞、M2巨噬细胞和记忆静息CD4 T细胞。在多变量分析中，我们确定晚期N分期和γδ T细胞的存在是生存较差的独立预测因素。（4）结论：我们发现肿瘤微环境中的γδ T细胞是未经治疗的HNSCC患者生存的负性预测因素。我们的研究结果强调需要更好地了解γδ T细胞在HNSCC中的作用，包括潜在的促肿瘤机制，以及它们的存在是否可预测替代治疗方法的需求。
