Immune Cell Deconvolution Reveals Possible Association of γδ T Cells with Poor Survival in Head and Neck Squamous Cell Carcinoma.
Immune Cell Deconvolution Reveals Possible Association of γδ T Cells with Poor Survival in Head and Neck Squamous Cell Carcinoma.
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DOI：
10.3390/cancers15194855
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发表时间：
2023-10-05
期刊：
影响因子：
5.2
通讯作者：
Puram, Sidharth V.
中科院分区：
文献类型：
--
作者：
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.
关键词：
在头颈部鳞状细胞癌（HNSCC）中，针对免疫系统治疗的一个主要挑战是对罕见免疫细胞亚型的不完全了解。最近的一些研究探索了这些细胞类型，但这些研究没有将细胞数据与临床病理或人口学特征结合起来，从而在适当的临床背景下得出结论。我们对HNSCC患者的转录组数据进行反卷积，以推断免疫细胞亚型的比例，并将这些数据置于人口统计学、临床、病理和基因组特征的背景下。我们的分析揭示了γδ T细胞可能与HNSCC的低生存率相关，并强调需要更好地了解这些罕见细胞在HNSCC中的作用，包括γδ T细胞的存在是否可以预测辅助治疗的需要。(1)背景：罕见的免疫细胞亚型在许多实体肿瘤中的作用，其中以头颈部鳞状细胞癌（HNSCC）为主，尚未得到很好的定义。本研究的目的是评估HNSCC中常见和罕见免疫细胞亚型的比例与生存结果之间的关系。(2)方法：在本队列研究中，我们利用基于CIBERSORT算法和LM22签名矩阵的反卷积方法，从癌症基因组图谱中推断517例未经治疗的hpv阴性HNSCC患者的免疫细胞亚型比例。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：我们对大多数患者的22种免疫细胞亚型进行了可靠的解卷积，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，我们确定了晚期N期和γδ T细胞的存在是较差生存率的独立预测因素。(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患者生存的负面预测因子。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，包括潜在的致瘤机制，以及它们的存在是否可以预测替代治疗方法的需要。
In head and neck squamous cell carcinoma (HNSCC), a major challenge with treatments targeting the immune system is an incomplete understanding of rare immune cell subtypes. Several recent studies have explored these cell types, but these studies have not integrated cellular data with clinicopathologic or demographic features to place conclusions in an appropriate clinical context. We deconvolve transcriptomic data from HNSCC patients to infer proportions of immune cell subtypes and place these data in the context of demographic, clinical, pathologic, and genomic characteristics. Our analysis revealed a possible association of γδ T cells with poor survival in HNSCC and underscore the need to better understand the role of these rare cells in HNSCC, including whether the presence of γδ T cells may predict the need for adjuvant therapy. (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.
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