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Novel non-terminal tumor sampling procedure using fine needle aspiration supports immuno-oncology biomarker discovery
Suzanne Isabelle Sitnikova1, Sophie Munnings-Tomes2, Elena Galvani2
1AstraZeneca, Cambridge, UK suzanne.sitnikova@astrazeneca.com.
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.
Insights
Researchers developed a new minimally invasive fine needle aspiration technique for repeated tumor microenvironment (TME) sampling in mice. This method links TME biomarkers to treatment outcomes, improving preclinical cancer research and reducing animal use.
Area of Science:
- Oncology
- Immunology
- Preclinical Research
Background:
- Immuno-oncology is a standard cancer therapy, but response rates vary.
- Identifying biomarkers for treatment response is crucial.
- Current methods for analyzing tumor microenvironment (TME) biomarkers in mice are terminal, preventing outcome correlation.
Purpose of the Study:
- To develop and validate a novel, non-terminal tumor sampling method for preclinical mouse models.
- To enable repeated biopsy of the TME via fine needle aspiration.
- To link TME biomarkers directly to treatment response outcomes.
Main Methods:
- Developed and validated a fine needle aspiration technique for non-terminal tumor sampling in mice.
- Utilized repeated in-life sampling of subcutaneous flank tumors.
- Analyzed TME using flow cytometry and single-cell transcriptomics.
Main Results:
- The fine needle aspiration technique yields sufficient material for immune cell analysis.
- Demonstrated the ability to link TME biomarkers to treatment response outcomes.
- This method allows for paired evaluation of biomarkers and outcomes, unlike terminal sampling.
Conclusions:
- This minimally invasive technique refines pharmacodynamic analysis of the TME.
- Facilitates paired evaluation of treatment response biomarkers with outcomes.
- Reduces the number of animals required in preclinical research.
