Department of Otorhinolaryngology, Saarland University Medical Center, Homburg, Saar, Germany.
Institute of Virology, Saarland University Medical Center, Homburg, Saar, Germany.
Front Immunol. 2023 Jun 13;14:1172768. doi: 10.3389/fimmu.2023.1172768. eCollection 2023.
Due to the expanding role of immune checkpoint inhibition in the treatment of head and neck squamous cell carcinoma, understanding immunological processes in the tumor microevironment (TME) has strong translational importance. Though analytical methods for a comprehensive analysis of the immunological TME have constantly improved and expanded over the past years the prognostic relevance of immune cell composition in head and neck cancer TME largely remains ambiguous with most studies focusing on one or a small subset of immune cells.
The overall survival (OS) of the TCGA-HNSC patient cohort comprising 513 head and neck cancer patients was correlated with a total of 29 different immune metrics including a wide spectrum of immune cell subpopulations as well as immune checkpoint receptors and cytokines using RNAseq based immune deconvolution analyses. The most significant predictors of survival among these 29 immune metrics were validated on a separate HNSCC patient cohort (n=101) using immunohistochemistry: CD3, CD20+CXCR5, CD4+CXCR5, Foxp3 and CD68.
Overall immune infiltration irrespective of immune cell composition showed no significant correlation with the patients' overall survival in the TCGA-HNSC cohort. However, when focusing on different immune cell subpopulations, naïve B cells (p=0.0006), follicular T-helper cells (p<0.0001), macrophages (p=0.0042), regulatory T cells (p=0.0306), lymphocytes (p=0.0001), and cytotoxic T cells (p=0.0242) were identified as highly significant predictors of improved patient survival. Using immunohistochemical detection of these immune cells in a second independent validation cohort of 101 HNSCC patients, we confirmed the prognostic relevance of follicular T helper cells, cytotoxic T cells and lymphocytes. In multivariable analysis, HPV negativity and advanced UICC stages were identified as additional prognostic biomarkers associated with poor outcome.
Our study highlights the prognostic relevance of the immunological tumor environment in head and neck cancer and demonstrates that a more detailed analysis of immune cell composition and immune cell subtypes is necessary to accurately prognosticate. We observed the highest prognostic relevance for lymphocytes, cytotoxic T cells, and follicular T helper cells, suggesting further investigations focusing on these specific immune cell subpopulations not only as predictors of patient prognosis but also as promising targets of new immunotherapeutic strategies.
由于免疫检查点抑制在头颈部鳞状细胞癌治疗中的作用不断扩大，因此了解肿瘤微环境（TME）中的免疫过程具有很强的转化意义。尽管近年来用于全面分析免疫 TME 的分析方法不断改进和扩展，但头颈部癌症 TME 中免疫细胞组成的预后相关性仍存在很大的不确定性，大多数研究仅关注一种或少数几种免疫细胞。
TCGA-HNSC 患者队列（共 513 例头颈部癌症患者）的总生存期（OS）与总共 29 种不同的免疫指标相关联，这些指标包括广泛的免疫细胞亚群以及免疫检查点受体和细胞因子，使用基于 RNAseq 的免疫去卷积分析。在使用免疫组织化学在另一个 HNSCC 患者队列（n=101）中验证的这 29 个免疫指标中，最显著的生存预测因子是：CD3、CD20+CXCR5、CD4+CXCR5、Foxp3 和 CD68。
TCGA-HNSC 队列中，无论免疫细胞组成如何，整体免疫浸润均与患者的总生存期无显著相关性。然而，当关注不同的免疫细胞亚群时，幼稚 B 细胞（p=0.0006）、滤泡性 T 辅助细胞（p<0.0001）、巨噬细胞（p=0.0042）、调节性 T 细胞（p=0.0306）、淋巴细胞（p=0.0001）和细胞毒性 T 细胞（p=0.0242）被确定为改善患者生存的高度显著预测因子。在包含 101 例 HNSCC 患者的第二个独立验证队列中，使用这些免疫细胞的免疫组织化学检测，我们证实了滤泡性 T 辅助细胞、细胞毒性 T 细胞和淋巴细胞的预后相关性。在多变量分析中，HPV 阴性和 UICC 晚期被确定为与不良预后相关的其他预后生物标志物。
我们的研究强调了头颈部癌症中肿瘤免疫环境的预后相关性，并表明需要更详细地分析免疫细胞组成和免疫细胞亚型，以准确预测预后。我们观察到淋巴细胞、细胞毒性 T 细胞和滤泡性 T 辅助细胞的预后相关性最高，这表明进一步研究集中在这些特定的免疫细胞亚群上，不仅可以作为患者预后的预测因子，而且可以作为新的免疫治疗策略的有前途的靶点。
