“Predicting Immunotherapy Response with a New Test
Featuring: BostonGene
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“Predicting Immunotherapy Response with a New Test" (BostonGene) [#75] Adrienne Nugent and Brad Power November 1, 2023 “When we speak about multiplex immunofluorescence, we're mostly focused on the tumor microenvironment because we would like to provide a prediction of therapy response to immuno-oncology.
” – Katerina Postovalova “The tissue assay, the blood assay, the MxIF – we're trying to go deep to decode the cancer in unique cases to really understand what's driving response, or lack thereof.” – Michael Hensley Meeting Summary Advanced cancer patients need advanced testing to personalize and guide their treatment decisions.
Beyond the increasingly common DNA sequencing, there are emerging RNA sequencing and other tests which show your "tumor mutational burden", “microsatellite instability”, and mutational and immune landscapes. These state-of-the art tests are performed by certified labs.
They then apply sophisticated analytics and bioinformatics to the test data to generate comprehensive personalized reports on the unique molecular portrait of your cancer and your treatment options. These tests can tell you whether you will be a likely responder to a therapy.
For example, understanding the spatial relationships of where the various immune cells are within the tumor microenvironment is important if you are considering an immunotherapy. Katerina Postovalova is uniquely qualified to explain these novel tests. She is Head of Digital Pathology at BostonGene, a diagnostics company.
She can describe, for example, how BostonGene's "multiplex immunofluorescence" platform, in which many (30-50) labeled antibodies can be applied to your tumor tissue sample to provide a comprehensive overview of your tumor cells and tumor microenvironment. Michael Hensley is a Senior Strategic Account Manager at BostonGene, managing their relationship with MD Anderson.
Why should you care about newer tests of the tumor microenvironment? Understanding your tumor microenvironment – the spatial distribution of the cell types in your tumor tissue – can aid in predicting your response to immunotherapy and guide your treatment decisions.
A three-dimensional picture of your tumor microenvironment – the types of cells that are present in and around your tumor tissue, such as whether your immune cells are located primarily within important tumor niches or are isolated – can show whether an immunotherapy has a good or bad chance of killing your cancer cells.
For example, if your tumor has a high level of infiltration of immune cells, your tumor may be more likely to respond to immunotherapy. What can multiplex immunofluorescence tell you that is new and different?
Multiplex immunofluorescence is a complement to the more common tumor tests (an “oncopanel”, which looks at 100-300 driver genes), whole exome sequencing (about 20,000 genes/DNA which code proteins), and RNA (transcriptome) sequencing.
tell you that is new and different? Multiplex immunofluorescence is a complement to the more common tumor tests (an “oncopanel”, which looks at 100-300 driver genes), whole exome sequencing (about 20,000 genes/DNA which code proteins), and RNA (transcriptome) sequencing. The sequencing tests
“Predicting Immunotherapy Response with a New Test" (BostonGene) [#75] tell you about mutations in your tumor cells which are different from normal cells. Multiplex immunofluorescence is a technology that can stain up to 40 markers on a single slide of tissue, enabling a deeper analysis of the tumor microenvironment than traditional staining of tumor tissue.
Multiplex immunofluorescence can tell you the following about your tumor microenvironment: ●The presence or absence of different biomarkers, e.g., PD-L1 ●The different subtypes of immune cells ●The location of immune cells ●The distances between different cells ●The contacts between different cells What input do you need to provide?
You probably had a biopsy of your cancer at your diagnosis (the primary site), or maybe you have a more recent biopsy of a metastatic site. This will have been typically stored in a formalin- fixed paraffin-embedded (FFPE) block. Slides can be made from this tissue. Primary or metastatic tissue can be analyzed.
While tissue that has been stored for a long time can be used, samples older than five years may be less practical. Factors such as tumor purity and necrotic (dead) tissue can affect the ability to use tissue samples. Frozen tissue can also be used as it can then be embedded in paraffin. Importantly, tumor tissue must be stored in a block so that fresh-cut slides can be prepared.
Tumor tissue stored as slides will not work for this test. Tissue slides are a very precious resource, so an algorithm is used to predict the number of slides needed for tumor analysis. This ensures that each slide can be put to maximum use.
While tissue samples from multiple time points can be assessed to provide valuable insights into tumor response and evolution, the most informative sample to test would be the most recently available tissue. Does this test work for all cancer types? Multiplex immunofluorescence works well for all cancer types.
The only issue arises when there are unique preservation methods required for certain types of tissue. For example, if a metastatic site is in the bone, then the lab uses a specific solution to prepare the sample for multiplex immunofluorescence. Can the same tissue sample be used for typical tumor sequencing and multiplex immunofluorescence?
Each test requires a separate tissue sample for a separate workflow. Depending on the amount of tissue provided, the lab will use an algorithm to determine if there is enough tissue for both multiplex immunofluorescence and their standard tumor sequencing, which includes whole exome (DNA) and transcriptome (RNA) sequencing.
ssue sample for a separate workflow. Depending on the amount of tissue provided, the lab will use an algorithm to determine if there is enough tissue for both multiplex immunofluorescence and their standard tumor sequencing, which includes whole exome (DNA) and transcriptome (RNA) sequencing.
“Predicting Immunotherapy Response with a New Test" (BostonGene) [#75] The lab can also do immunoprofiling of blood samples. This is a comprehensive flow cytometry test (a laser-based technique used to detect and analyze the chemical and physical characteristics of cells or particles) used to describe immune fitness and can guide immunotherapy-based decisions.
To maximize your knowledge and inform your treatment decisions, you could get three tests: 1.Tumor Portrait : Whole exome and transcriptome (bulk RNA) sequencing to understand genomic and RNA expression alterations within the tumor. 2.Multiplex immunofluorescence - MxIF: spatial proteomics to characterize tumor tissue architecture and cell-to-cell interactions in the tumor microenvironment. 3.
Immunoprofiling : blood cell composition characterization to determine the immune cell types present in blood.
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You should always consult a doctor about your specific situation before pursuing any health care program, treatment, product or other course of action that might affect your health.
“Predicting Immunotherapy Response with a New Test" (BostonGene) [#75] Meeting Notes SUMMARY KEYWORDS tumor, tissue, immune cells, samples, work, tumor microenvironment, analyze, pdl, slides, patients, analysis, cells, stromal, clinical utility, immune, boston, sequencing, rna, gene, tissue sample SPEAKERS Katerina Postovalova (40%), Michael Hensley (18%), Rick Stanton (10%), Brad Power (9%), Allen Morris (8%), Brian McCloskey (7%), Gitte Pedersen (6%), David Plunkett (1%), Kaumudi Bhawe (1%) OUTLINE 1.
Immunotherapy analysis and treatment options for cancer patients. (0:00) 2.Analyzing multiplexed immunofluorescence images for cancer research. (6:07) 3.Analyzing audio transcripts for tumor microenvironment insights. (12:44) 4.Using spatial analysis for cancer treatment. (19:35) 5.Cancer biomarkers and tissue analysis. (23:55) 6.Cancer treatment and immune microenvironment. (34:00) 7.
Tissue analysis and immune profiling for cancer diagnosis. (36:00) 8.Tumor profiling and immune profiling in cancer treatment. (39:16) 9.Leveraging tissue samples for cancer treatment decisions. (41:41) 10.Immunotherapy treatment and tumor evolution. (45:39) 11.Validating biomarkers for cancer treatment using a platform. (48:52) 12.Validating biomarkers for cancer immunotherapy.
mmune profiling in cancer treatment. (39:16) 9.Leveraging tissue samples for cancer treatment decisions. (41:41) 10.Immunotherapy treatment and tumor evolution. (45:39) 11.Validating biomarkers for cancer treatment using a platform. (48:52) 12.Validating biomarkers for cancer immunotherapy. (50:21) 13.Prostate cancer diagnosis and immune response. (54:46) 14.
Using technology to analyze RNA data for cancer research. (1:01:43) 15.Cancer genomics and personalized medicine. (1:03:59) SUMMARY ●Immunotherapy analysis and treatment options for cancer patients. 0:00 ○BostonGene scientist Katerina Postovalova discusses cancer research with patients and caregivers. ○BostonGene: Leading immunotherapy analysis for prostate cancer treatment decisions.
○Multiplex fluorescence data analysis for tumor diagnosis. ●Analyzing multiplexed immunofluorescence images for cancer research. 6:07 ○Researcher uses Acquire Boston's pseudo-service provider for acquire to analyze tissue samples for immune cell subtypes and heterogeneity in tumor tissue.
○Researchers develop AI-based approach to analyze multiplexed fluorescence images of tissue samples to identify cell types and their distribution within the tumor.
“Predicting Immunotherapy Response with a New Test" (BostonGene) [#75] ○Analyze cell types in tumor microenvironment using 20-30 antibody panels. ●Analyzing audio transcripts for tumor microenvironment insights. 12:44 ○Katerina Postovalova highlights the limitations of bulk RNA sequencing data in understanding the spatial organization of tumors, citing examples from prostate cancer research.
○Katerina Postovalova emphasizes the importance of supplementing tumor positive polls with spatial analysis to predict therapy response to immune oncology, using multiplexing or fluorescence techniques to analyze the tumor microenvironment. ○Katerina Postovalova analyzes the distribution of stromal component and tumor cells in the tissue, noting less immune alterations in the malignant area.
○Katerina Postovalova presents a graph-based analysis of cellular niches and cell- to-cell interaction, highlighting the presence of different subtypes of immune cells in various segments of the tissue. ○Katerina Postovalova presents analysis of tumor imaging report, focusing on malignant cells and tumor microenvironment. ●Using spatial analysis for cancer treatment.
19:35 ○Rick Stanton praises Katarina's spatial analysis, hoping it will lead to directed therapies for prostate cancer patients. ○Rick Stanton discusses using 40-plex immunophenotyping to predict cancer response to treatment. ●Cancer biomarkers and tissue analysis. 23:55 ○Michael Hensley discusses using MX if to better understand why some tumors respond to immunotherapy while others do not.
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