Novel non-terminal tumor sampling procedure using fine needle aspiration supports immuno-oncology biomarker discovery in preclinical mouse models
Autor: | Kathy Mulgrew, Sophie Munnings-Tomes, Simon J. Dovedi, Chris M Rands, Matthew J Robinson, Judit España Agustí, Tianhui Zhang, Hormas Ghadially, Suzanne I. Sitnikova, Kristina M. Ilieva, Tim Slidel, Guglielmo Rosignoli, Elena Galvani, Robert W. Wilkinson, Stacy Kentner |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty Treatment response medicine.medical_treatment Biopsy Fine-Needle Immunology immunologic techniques Mice 03 medical and health sciences 0302 clinical medicine Immunologic Technique drug evaluation Cell Line Tumor Internal medicine Immunotherapy Biomarkers Biopsy preclinical Biomarkers Tumor medicine tumor microenvironment Animals Humans Immunology and Allergy Biomarker discovery RC254-282 Pharmacology Tumor microenvironment medicine.diagnostic_test business.industry Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cancer Immunotherapy medicine.disease Disease Models Animal 030104 developmental biology Fine-needle aspiration tumor biomarkers 030220 oncology & carcinogenesis Molecular Medicine business |
Zdroj: | Journal for ImmunoTherapy of Cancer, Vol 9, Iss 6 (2021) Journal for Immunotherapy of Cancer |
ISSN: | 2051-1426 |
Popis: | BackgroundImmuno-oncology therapies are now part of the standard of care for cancer in many indications. However, durable objective responses remain limited to a subset of patients. As such, there is a critical need to identify biomarkers that can predict or enrich for treatment response. So far, the majority of putative biomarkers consist of features of the tumor microenvironment (TME). However, in preclinical mouse models, the collection of tumor tissue for this type of analysis is a terminal procedure, obviating the ability to directly link potential biomarkers to long-term treatment outcomes.MethodsTo address this, we developed and validated a novel non-terminal tumor sampling method to enable biopsy of the TME in mouse models based on fine needle aspiration.ResultsWe show that this technique enables repeated in-life sampling of subcutaneous flank tumors and yields sufficient material to support downstream analyses of tumor-infiltrating immune cells using methods such as flow cytometry and single-cell transcriptomics. Moreover, using this technique we demonstrate that we can link TME biomarkers to treatment response outcomes, which is not possible using the current method of terminal tumor sampling.ConclusionThus, this minimally invasive technique is an important refinement for the pharmacodynamic analysis of the TME facilitating paired evaluation of treatment response biomarkers with outcomes and reducing the number of animals used in preclinical research. |
Databáze: | OpenAIRE |
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