한빛사논문
- 조회662
Chang Gon Kim1†, Min Hee Hong1†, Dahee Kim2†, Brian Hyohyoung Lee3,4†, Hyunwook Kim1†, Chan-Young Ock5†, Geoffrey Kelly3, Yoon Ji Bang4, Gamin Kim1, Jung Eun Lee1, Chaeyeon Kim1, Se-Heon Kim2, Hyun Jun Hong2, Young Min Park2, Nam Suk Sim2, Heejung Park6, Jin Woo Park6, Chang Geol Lee7, Kyung Hwan Kim7, Goeun Park8, Inkyung Jung8, Dawoon Han9, Jong Hoon Kim9, Junha Cha10, Insuk Lee10, Mingu Kang5, Heon Song5, Chiyoon Oum5, Seulki Kim5, Sukjun Kim5, Yoojoo Lim5, Seunghee Kim-Schulze3,11, Miriam Merad3,11,12, Sun Och Yoon6*, Hyun Je Kim4,13,14,15*, Yoon Woo Koh2*, Hye Ryun Kim1*
1Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
2Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea
3Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA
4Department of Biomedical Science, Seoul National University College of Medicine, Seoul, Republic of Korea
5Lunit Inc., Seoul, Republic of Korea
6Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea
7Department of Radiation Oncology, Yonsei Cancer Center, Heavy Ion Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
8Division of Biostatistics, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea
9Department of Dermatology and Cutaneous Biology Research Institute, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
10Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea
11Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA
12Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
13Genome Medicine Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
14Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
15Seoul National University Hospital, Seoul, Republic of Korea
†Equally contributed
*Corresponding authors : Prof. Hye Ryun Kim, Prof. Yoon Woo Koh, Prof. Hyun Je Kim, Prof. Sun Och Yoon
Abstract
Purpose: Clinical implications of neoadjuvant immunotherapy in patients with locally advanced but resectable head and neck squamous cell carcinoma (HNSCC) remain largely unexplored.
Patients and methods: 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.
Results: 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.
Conclusions: 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.
논문정보
- Research article
- 2024년 03월 (BRIC 등록일 2024-03-11)
- 국내(교신)+국외 연구진
- 의약학 > 종양의학
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