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UBC Theses and Dissertations

Tissue-based methods to assess immune biomarkers within the tumor microenvironment on formalin fixed paraffin embedded clinical materials Shenasa, Elahe

Abstract

The tumor immune microenvironment plays a critical role in determining responses to immune-modulatory treatments, including certain types of cytotoxic chemotherapy and the new generation of immunotherapies. Given the severe and potentially long-term side effects these therapies can confer, there is an urgent need for effective immune biomarkers capable of selecting those patients who are most likely to benefit from such treatments. This thesis explores a range of methods, from standard hematoxylin and eosin staining to advanced high-plex digital spatial technologies, to study the immune microenvironment on human tumor tissue specimens and evaluate biomarkers with clinical relevance. Chapter 2 and 3 focus on assessing the prognostic and predictive values of immune biomarkers when applied to materials from randomized phase III clinical trials involving breast cancer patients. These chapters utilize and compare various techniques, including histology, immunohistochemistry, and multiplex digital spatial profiling, applied to clinical samples in tissue microarray and full-face section formats linked to treatment and long-term outcome data. Chapter 4 investigates methods with spatial capacity to detect tertiary lymphoid structures, a key biomarker associated with significant prognostic and predictive value for immunotherapy benefits, particularly in sarcomas. This chapter compares the effectiveness of tissue microarrays versus full-face sections in identifying tertiary lymphoid structures, highlighting the strengths and limitations of different approaches.

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Attribution-NonCommercial-NoDerivatives 4.0 International