The curative treatment of multiple solid tumors, including head and neck squamous cell carcinoma (HNSCC), utilizes radiation. The outcomes for HPV/p16-negative HNSCC are significantly worse than HPV/p16-positive tumors, with increased radiation resistance leading to worse locoregional recurrence (LRR) and ultimately death. This study analyzed the relationship between immune function and outcomes following radiation in HPV/p16-negative tumors to identify mechanisms of radiation resistance and prognostic immune biomarkers. A discovery cohort of 94 patients with HNSCC treated uniformly with surgery and adjuvant radiation and a validation cohort of 97 similarly treated patients were utilized. Tumor immune infiltrates were derived from RNAseq gene expression. The immune cell types significantly associated with outcomes in the discovery cohort were examined in the independent validation cohort. A positive association between high Th2 infiltration and LRR was identified in the discovery cohort and validated in the validation cohort. Tumor mutations in CREBBP/EP300 and CASP8 were significantly associated with Th2 infiltration. A pathway analysis of genes correlated with Th2 cells revealed the potential repression of the antitumor immune response and the activation of BRCA1-associated DNA damage repair in multiple cohorts. The Th2 infiltrates were enriched in the HPV/p16-negative HNSCC tumors and associated with LRR and mutations in CASP8, CREBBP/EP300, and pathways previously shown to impact the response to radiation.
针对包括头颈部鳞状细胞癌（HNSCC）在内的多种实体瘤，放射治疗是一种重要的根治性手段。HPV/p16阴性HNSCC患者的预后显著差于HPV/p16阳性肿瘤患者，其放射抵抗性增强导致局部区域复发率升高，最终增加死亡风险。本研究旨在分析HPV/p16阴性肿瘤中免疫功能与放疗后预后的关系，以揭示放射抵抗机制并寻找预后相关的免疫生物标志物。研究纳入94例接受统一手术及辅助放疗的HNSCC患者作为发现队列，另设97例接受相似治疗的验证队列。通过RNA测序基因表达数据推演肿瘤免疫浸润情况，将在发现队列中与预后显著相关的免疫细胞类型在独立验证队列中进行验证。研究发现，高Th2细胞浸润与局部区域复发呈正相关，该结果在发现队列中得到确认并在验证队列中获得验证。CREBBP/EP300和CASP8基因的肿瘤突变与Th2细胞浸润显著相关。对Th2细胞相关基因的通路分析显示，多个队列中均存在抗肿瘤免疫应答潜在抑制及BRCA1相关DNA损伤修复激活的现象。Th2细胞浸润在HPV/p16阴性HNSCC肿瘤中富集，并与局部区域复发、CASP8和CREBBP/EP300基因突变以及既往研究证实影响放疗反应的通路改变相关。
Th2 Cells Are Associated with Tumor Recurrence Following Radiation
肿瘤(癌症)患者之家