Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea.
Clin Cancer Res. 2024 May 15;30(10):2097-2110. doi: 10.1158/1078-0432.CCR-23-3249.
Clinical implications of neoadjuvant immunotherapy in patients with locally advanced but resectable head and neck squamous cell carcinoma (HNSCC) remain largely unexplored.
Patients with resectable HNSCC were randomized to receive a single dose of preoperative durvalumab (D) with or without tremelimumab (T) before resection, followed by postoperative (chemo)radiotherapy based on multidisciplinary discretion and 1-year D treatment. Artificial intelligence (AI)-powered spatial distribution analysis of tumor-infiltrating lymphocytes and high-dimensional profiling of circulating immune cells tracked dynamic intratumoral and systemic immune responses.
Of the 48 patients enrolled (D, 24 patients; D+T, 24 patients), 45 underwent surgical resection per protocol (D, 21 patients; D+T, 24 patients). D±T had a favorable safety profile and did not delay surgery. Distant recurrence-free survival (DRFS) was significantly better in patients treated with D+T than in those treated with D monotherapy. AI-powered whole-slide image analysis demonstrated that D+T significantly reshaped the tumor microenvironment toward immune-inflamed phenotypes, in contrast with the D monotherapy or cytotoxic chemotherapy. High-dimensional profiling of circulating immune cells revealed a significant expansion of T-cell subsets characterized by proliferation and activation in response to D+T therapy, which was rare following D monotherapy. Importantly, expansion of specific clusters in CD8+ T cells and non-regulatory CD4+ T cells with activation and exhaustion programs was associated with prolonged DRFS in patients treated with D+T.
Preoperative D±T is feasible and may benefit patients with resectable HNSCC. Distinct changes in the tumor microenvironment and circulating immune cells were induced by each treatment regimen, warranting further investigation.
新辅助免疫疗法在局部晚期可切除头颈部鳞状细胞癌（HNSCC）患者中的临床意义仍在很大程度上尚未得到探索。
将可切除的 HNSCC 患者随机分为两组，分别在术前接受单次 durvalumab（D）加或不加 tremelimumab（T）治疗，然后根据多学科的判断进行术后（化疗）放疗，并接受为期 1 年的 D 治疗。人工智能（AI）驱动的肿瘤浸润淋巴细胞空间分布分析和循环免疫细胞的高维分析可跟踪肿瘤内和全身免疫反应的动态变化。
48 例患者入组（D 组 24 例，D+T 组 24 例），其中 45 例患者按方案接受了手术切除（D 组 21 例，D+T 组 24 例）。D±T 具有良好的安全性，且不会延迟手术。与 D 单药治疗相比，D+T 治疗的患者无远处复发生存（DRFS）显著改善。AI 驱动的全切片图像分析表明，与 D 单药或细胞毒性化疗相比，D+T 显著重塑了肿瘤微环境，向免疫浸润表型转变。高维循环免疫细胞分析显示，D+T 治疗后 T 细胞亚群显著扩增，具有增殖和激活特征，而 D 单药治疗后则很少见。重要的是，CD8+T 细胞和非调节性 CD4+T 细胞中具有激活和衰竭程序的特定簇的扩增与 D+T 治疗患者的 DRFS 延长相关。
术前 D±T 是可行的，可能使可切除的 HNSCC 患者受益。两种治疗方案均引起肿瘤微环境和循环免疫细胞的明显变化，值得进一步研究。
