ACCESS
Review Article
Volume 3, Article ID: 2026.0026
Yu Liu
yuliu23@connect.hku.hk
Xiaotong You
xiaotongyou@connect.hku.hk
Chuzi Mo
mcz878mcz@connect.hku.hk
Xiaohu Hao
xiaohu_hao@aliyun.com
1 Faculty of Dentistry, The University of Hong Kong, Sai Ying Pun, Hong Kong.
2 Department of Thoracic Surgery and Institute of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
3 Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, Chengdu, Sichuan 610041, China.
* Author to whom correspondence should be addressed
Received: 22 Nov 2025 Accepted: 30 May 2026 Available Online: 31 May 2026
This article is part of the Special Issue Spatial Omics in Cancer: Decoding Heterogeneity, Microenvironment Crosstalk, and Therapeutic Implications
Head and neck squamous cell carcinoma (HNSCC) is characterized by a highly heterogeneous tumor microenvironment (TME) that drives disease progression and therapeutic resistance. The emergence of spatial omics technology, encompassing spatial transcriptomics, proteomics, metabolomics and multi-modal imaging, has revolutionized our understanding of TME by preserving the critical spatial architecture of molecular landscapes. This review synthesizes key innovations derived from spatial omics in HNSCC TME, detailing the organised spatial distribution of malignant cell states, the functional organization of immune cells (e.g., tertiary lymphoid structures vs. suppressive stromal niches), and the pivotal roles of heterogeneous cancer-associated fibroblasts (CAFs) and abnormal vasculature. We further decipher spatially resolved intercellular communication networks that mediate drug resistance mechanisms to immunotherapy, and targeted therapy. Finally, we address current methodological constraints and discuss the transformative potential of integrating artificial intelligence with spatial data to refine patient stratification and personalize therapeutic strategies.
Disclaimer: This is not the final version of the article. Changes may occur when the manuscript is published in its final format.