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Methods for assessment of the tumour microenvironment and immune interactions in non-small cell lung cancer. A
Kanishka Rangamuwa1,2, Christian Aloe3, Michael Christie4
1Department of Respiratory Medicine, Royal Melbourne Hospital, Melbourne, VIC, Australia.
Abstract:
Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer death worldwide. Immunotherapy with immune checkpoint inhibitors (ICI) has significantly improved outcomes in some patients, however 80-85% of patients receiving immunotherapy develop primary resistance, manifesting as a lack of response to therapy. Of those that do have an initial response, disease progression may occur due to acquired resistance. The make-up of the tumour microenvironment (TME) and the interaction between tumour infiltrating immune cells and cancer cells can have a large impact on the response to immunotherapy. Robust assessment of the TME with accurate and reproducible methods is vital to understanding mechanisms of immunotherapy resistance. In this paper we will review the evidence of several methodologies to assess the TME, including multiplex immunohistochemistry, imaging mass cytometry, flow cytometry, mass cytometry and RNA sequencing.
Insights
Non-small cell lung cancer (NSCLC) immunotherapy resistance is common. Understanding the tumor microenvironment (TME) using advanced methods like multiplex IHC and RNA sequencing is crucial for improving treatment response.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Non-small cell lung cancer (NSCLC) remains a major global health challenge.
- Immunotherapy with immune checkpoint inhibitors (ICI) offers improved outcomes for some NSCLC patients.
- Primary and acquired resistance to ICI therapy affects a significant majority of patients, necessitating further research into resistance mechanisms.
Purpose of the Study:
- To review current methodologies for assessing the tumor microenvironment (TME) in NSCLC.
- To highlight the importance of TME assessment in understanding and overcoming immunotherapy resistance.
- To discuss the evidence supporting various techniques for robust TME analysis.
Main Methods:
- Review of existing literature on TME assessment techniques.
- Discussion of multiplex immunohistochemistry (IHC) for spatial analysis of immune cells.
- Evaluation of imaging mass cytometry, flow cytometry, mass cytometry, and RNA sequencing for comprehensive TME profiling.
Main Results:
- The TME composition and immune cell interactions significantly influence immunotherapy response in NSCLC.
- Accurate and reproducible TME assessment is vital for identifying biomarkers of resistance.
- Multiple advanced techniques offer complementary insights into the complex TME.
Conclusions:
- Robust assessment of the TME is essential for developing strategies to overcome immunotherapy resistance in NSCLC.
- Multiplex IHC, imaging mass cytometry, flow cytometry, mass cytometry, and RNA sequencing are key technologies for TME analysis.
- Further research utilizing these methods will advance our understanding of ICI resistance and improve patient outcomes.
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