CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Clinical Significance of Tumor Infiltrating T-Helper and Regulatory Cells in Bulgarian Cervical Cancer Patients.
Clinical Significance of Tumor Infiltrating T-Helper and Regulatory Cells in Bulgarian Cervical Cancer Patients.
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宫颈癌（CC）主要由人乳头瘤病毒（HPV）感染引起，是最常见的妇科恶性肿瘤，也是女性癌症相关死亡的主要原因之一。免疫微环境，尤其是 CD4+ T 辅助细胞和 FOXP3（forkhead box P3）+ 调节性 T 细胞（Tregs），在肿瘤进展中发挥关键作用。然而，免疫细胞浸润与 CC 临床结局之间的确切关系尚未完全明确。本研究旨在探讨 CC 患者中 CD4+ T 辅助细胞、FOXP3+ Tregs 与临床/病理参数之间的关联。
我们对 2015 年至 2021 年间诊断的 150 例 T1 期宫颈癌患者进行了回顾性分析。使用免疫组织化学（IHC）评估肿瘤样本中肿瘤内和间质区域的 CD4+ 和 FOXP3+ TILs。此外，使用 TCGA 队列的去卷积转录组数据评估肿瘤免疫微环境（TIME）中的免疫浸润。
CD4+ T 辅助细胞高浸润与淋巴结阴性 CC 患者更好的总生存期（OS）显著相关（p = 0.0006）。然而，未发现 Tregs 具有显著的预后价值。CD4+ 细胞在高分化肿瘤（G1 和 G2）患者中更为常见，且与其他组织学亚型相比，鳞状细胞癌（SCC）中 CD4+ 浸润水平较低。多因素回归分析显示，仅肿瘤大小（T1b3）和未分化肿瘤形态（G3）与较差的 OS 显著相关。相比之下，在调整临床因素后，CD4+ 或 FOXP3+ 细胞浸润与 OS 无显著相关性。癌症死亡的竞争风险分析显示与免疫细胞浸润水平无显著关联。
本研究强调了CC中免疫细胞浸润与临床结局之间的复杂关系。虽然CD4+ T辅助细胞浸润与淋巴结阴性病例的预后改善相关，但仍需进一步研究以阐明Tregs及其他免疫成分在肿瘤微环境中的作用。这些发现提示了CC中潜在的治疗策略方向，包括免疫检查点抑制剂。
Background and Objectives: Cervical cancer (CC), primarily caused by human papillomavirus (HPV) infection, is the most common gynecological cancer and a leading cause of cancer-related death in women. The immune microenvironment, particularly CD4+ T-helper cells and FOXP3 (forkhead box P3)+ regulatory T cells (Tregs), plays a crucial role in tumor progression.
However, the exact relationship between immune cell infiltration and clinical outcomes in CC is not fully understood.
This study aimed to examine the association between CD4+ T-helper cells, FOXP3+ Tregs, and clinical/pathological parameters in CC patients. Methods: We conducted a retrospective analysis of 150 patients with T1-stage cervical cancers diagnosed between 2015 and 2021. Tumor samples were evaluated using immunohistochemistry (IHC) to assess CD4+ and FOXP3+ TILs in intratumoral and stromal regions.
Additionally, deconvoluted transcriptomic data from the TCGA cohort were used to assess immune infiltration within the tumor immune microenvironment (TIME). Results: High infiltration of CD4+ T-helper cells was significantly associated with better overall survival (OS) in node-negative CC patients ( p = 0. 0006).
However, no significant prognostic value was found for Tregs. CD4+ cells were more prevalent in patients with well-differentiated tumors (G1 and G2) and lower levels of CD4+ infiltration were found in squamous cell carcinoma (SCC) compared to other histological subtypes. Multivariate regression analysis showed that only tumor size (T1b3) and undifferentiated tumor morphology (G3) were significantly associated with poorer OS. In contrast, infiltration of CD4+ or FOXP3+ cells did not significantly correlate with OS after adjusting for clinical factors.
Competing risk analysis for death from cancer showed no significant associations with immune cell infiltration levels. Conclusions: This study underscores the complex relationship between immune cell infiltration and clinical outcomes in CC. While CD4+ T-helper cell infiltration is associated with improved prognosis in node-negative cases, further research is necessary to clarify the role of Tregs and other immune components in the tumor microenvironment.
These findings suggest potential avenues for therapeutic strategies, including immune checkpoint inhibitors, in CC.
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