Establishment and multi-omics characterization of a PD-1-resistant murine esophageal squamous cell carcinoma cell line

  • Biochem Biophys Res Commun. 2026 Aug 27:828:154109. doi: 10.1016/j.bbrc.2026.154109.
Yi Xu  1 ,  Xianhao Wang  1 ,  Yujiao Sun  2 ,  Xinyi Ye  3 ,  Yingyin Gao  4 ,  Luxi Li  3 ,  Yue Wu  3 ,  Keyi Zhou  1 ,  Yunzhi Pan  5 ,  Sai Ma  6
Affiliations
  • 1. Department of Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, Suzhou, 215008, China.
  • 2. Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, China; Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, China.
  • 3. Department of Science and Technology, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, 215009, China; Department of Pharmacy, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, 215007, China; College of Pharmaceutical Sciences, Soochow University, Suzhou, 215127, China.
  • 4. Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, China; The Affiliated Traditional Chinese Medicine Hospital Guangzhou Medical University Guangzhou, Guangzhou, 511436, China.
  • 5. Department of Science and Technology, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, 215009, China; Department of Pharmacy, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, 215007, China; College of Pharmaceutical Sciences, Soochow University, Suzhou, 215127, China. Electronic address: [email protected].
  • 6. Department of Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, Suzhou, 215008, China. Electronic address: [email protected].
PMID: 42259198 DOI: 10.1016/j.bbrc.2026.154109
Abstract

Immunotherapy has revolutionized the treatment of esophageal squamous cell carcinoma (ESCC), but its clinical application is limited by low response rates and acquired resistance. The exploration of underlying is hampered by the absence of preclinical models that faithfully recapitulate the immune microenvironment and drug-resistant features of ESCC. Here, we established a novel murine ESCC cell line named mESCC-030, which was derived from primary ESCC tumors induced by 4-Nitroquinoline N-oxide (4-NQO) in C57BL/6 mice via consecutive in vivo selection. This cell line was validated by morphological observation and STR identification. Compared with primary parental cells, mESCC-030 exhibits stronger malignant proliferation, invasion and migration capabilities, and achieves 100% subcutaneous tumorigenicity in C57BL/6 mice. Moreover, the syngeneic graft tumors derived from this cell line display prominent resistance to PD-1 antibody therapy. Bulk transcriptomic profiling revealed that this cell line harbors enhanced proliferation-related pathways and diminished immune response pathways. Single-cell RNA Sequencing of graft tumors identified a highly proliferative cell cluster in tumor tissues, along with an extremely low proportion of immune infiltrating cells. Taken together, the mESCC-30 cell line and its syngeneic tumors represent a typical immune-cold tumor model, providing a novel platform to uncover immunotherapy resistance mechanisms and develop combination therapeutic strategies.

Keywords
Esophageal squamous cell carcinoma (ESCC); Immune-cold tumor; Murine cell line; Murine syngeneic model; PD-1 resistance.
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