2. Academic Validation
  3. Immunological dynamics in orthotopic compared with subcutaneous murine models of HPV-positive oropharyngeal cancer

Immunological dynamics in orthotopic compared with subcutaneous murine models of HPV-positive oropharyngeal cancer

  • Dis Model Mech. 2025 Dec 1;18(12):dmm052311. doi: 10.1242/dmm.052311.
Minzi Mao 1,  Ke Qiu 1,  Lan Feng 1,  Yao Song 1,  Yufang Rao 1,  Shuo Li 1,  Danni Cheng 1,  Xiuli Shao 1,  Chuanhuan Jiang 1 2,  Shenglan You 3,  Wei Xu 4,  Geoffrey Liu 5,  Jadwiga Jablonska 6,  Stephan Lang 6,  Shuaicheng Li 7,  Fei Chen 1,  Yu Zhao 1,  Jianjun Ren 1
Affiliations

Affiliations

  • 1 Department of Oto-Rhino-Laryngology, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan, China.
  • 2 Research Core Facility of West China Hospital, Sichuan University, Chengdu, 610041 Sichuan, China.
  • 3 Animal Imaging Core Facilities, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan, China.
  • 4 Department of Biostatistics, Princess Margaret Cancer Centre and Dalla Lana School of Public Health, M5G 2C1 Toronto, Ontario, Canada.
  • 5 Department of Medicine, Division of Medical Oncology and Hematology, Princess Margaret Cancer Center, University Health Network, University of Toronto, M5G 2C1 Toronto, Canada.
  • 6 Translational Oncology, Department of Otolaryngology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.
  • 7 Department of Computer Science, City University of Hong Kong, 999077 Hong Kong, China.
PMID: 40899264 DOI: 10.1242/dmm.052311
Abstract

The necessity of reliable preclinical models for evaluating the efficacy of novel therapeutic strategies is imperative. Nevertheless, the degree to which tumor-bearing murine models represent the immunological characteristics of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) has largely been unexplored. By utilizing single-cell RNA Sequencing technology, our research elucidated that subcutaneous (SC) murine models more accurately reflect the early immunogenic phase of human HPV-positive OPSCC, marked by a stage-dependent increase in effector T-cell infiltration. By contrast, orthotopic (base of tongue, BOT) tumors exhibited a progressive decline of cytotoxic T cells and accumulation of myeloid-derived suppressive cells, paralleling the immune decrease observed in advanced, immune-excluded human tumors. Additionally, our drug responsiveness analysis indicated that early-stage BOT models more accurately replicate the response to PDCD1 blockade, whereas late-stage SC models more accurately mirror the response to CTLA4 blockade akin to human samples. Our findings provide pivotal insights into the suitability of murine models for the preclinical assessment of immunotherapies in HPV-positive OPSCC.

Keywords

Drug sensitivity; Human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (OPSCC); Murine models; Tumor immune microenvironment (TIME).

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