作者
Chang Gon Kim,Min Hee Hong,Da Hee Kim,Brian Lee,Hyunwook Kim,Chan‐Young Ock,Geoffrey Kelly,Yoon Ji Bang,Gamin Kim,Jung Eun Lee,C. Kim,Se‐Heon Kim,Hyeyoung Hong,Young Min Park,Nam Suk Sim,HeeJung Park,Jin Woo Park,Chang Geol Lee,Kyung Hwan Kim,Goeun Park,Inkyung Jung,D.H. Han,J.H. Kim,Junha Cha,Insuk Lee,Mei Kang,Heon Song,Chiyoon Oum,Seulki Kim,Sukjun Kim,Yoojoo Lim,Seunghee Kim‐Schulze,Miriam Mérad,Sun Och Yoon,Hyun Je Kim,Yoon Woo Koh,Hye Ryun Kim
摘要
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)radiation 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 to 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.