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Yongliang Niu,1,* Bowen Ding,2,* Jingfeng Shi,1,* Ying Yang,3 Jian Zhao,4 Diming Wang5 1Department of Respiratory and Critical Care Medicine, No.2 People’s Hospital of Fuyang City, Fuyang Infectious Disease Clinical College of Anhui Medical University, Fuyang, 236000, People’s Republic of China; 2Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, People’s Republic of China; 3Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4Department of Thoracic Surgery, Anhui Chest Hospital, Hefei, 230022,People’s Republic of China; 5Department of Oncology, Anhui Chest Hospital, Hefei, 230022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Diming Wang, Department of Oncology, Anhui Chest Hospital, Hefei, 230022, People’s Republic of China, Email wdm15077909580@163.com Jian Zhao, Department of Thoracic Surgery, Anhui Chest Hospital, Hefei, 230022, People’s Republic of China, Email ahhfzj121103@126.comAbstract: Anaplastic lymphoma kinase (ALK) rearrangement represents a rare molecular subtype of lung squamous cell carcinoma (LSCC). Although ALK tyrosine kinase inhibitors (TKIs) are established as first-line therapy for advanced ALK-rearranged non-small cell lung cancer (NSCLC), their efficacy in LSCC appears inferior to that in adenocarcinoma. Furthermore, the clinical benefit of chemoimmunotherapy in this rare population remains poorly defined. Here, we report a case of ALK-rearranged LSCC exhibiting primary resistance to ALK-TKI therapy but achieving a remarkable and durable response to combined chemotherapy and immunotherapy, leading to long-term disease control. This case highlights the potential therapeutic benefit of chemoimmunotherapy in ALK-rearranged lung squamous cell carcinoma and suggests that it may represent a viable priority option worthy of exploration in advanced settings.Keywords: anaplastic lymphoma kinase, ALK, lung squamous cell carcinoma, chemoimmunotherapy