RT Journal Article
SR Electronic
T1 Novel non-terminal tumor sampling procedure using fine needle aspiration supports immuno-oncology biomarker discovery in preclinical mouse models
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP e002894
DO 10.1136/jitc-2021-002894
VO 9
IS 6
A1 Suzanne Isabelle Sitnikova
A1 Sophie Munnings-Tomes
A1 Elena Galvani
A1 Stacy Kentner
A1 Kathy Mulgrew
A1 Chris Rands
A1 Judit España Agustí
A1 Tianhui Zhang
A1 Kristina M Ilieva
A1 Guglielmo Rosignoli
A1 Hormas Ghadially
A1 Matthew J Robinson
A1 Tim Slidel
A1 Robert W Wilkinson
A1 Simon J Dovedi
YR 2021
UL http://jitc.bmj.com/content/9/6/e002894.abstract
AB Background Immuno-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.Methods To 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.Results We 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.Conclusion Thus, 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.All data relevant to the study are included in the article or uploaded as online supplemental information.