New Test to Predict Immunotherapy Response in Cancer Patients
Featuring: Katerina Postovalova, Head of Digital Pathology at BostonGene; Michael Hensley, Senior Strategic Account Manager at BostonGene
In short
A new test called multiplex immunofluorescence (MxIF) can map the immune cells inside your tumor tissue — showing not just which immune cells are present, but where they are and how they interact — to help predict whether immunotherapy is likely to work for you. Scientists from BostonGene explain how this test complements standard DNA and RNA sequencing, what kind of tissue sample you need, and how a blood-based immune profile can add even more information to guide treatment decisions.
- •Ask your care team whether your stored tumor tissue (ideally in a paraffin block, not older than five years) could be used for MxIF testing alongside standard DNA/RNA sequencing.
- •MxIF works across all cancer types and can analyze both primary tumor tissue and tissue from a metastatic site — the most recently collected sample tends to be the most informative.
- •Tumor tissue must be stored as a block, not as pre-cut slides, for MxIF to work; confirm with your hospital how your biopsy was stored.
- •A blood-based immunoprofiling test (flow cytometry) can be done alongside tissue testing to give a fuller picture of your immune system's readiness to respond to immunotherapy.
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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.
The sequencing tests 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.
•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. 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. The information and opinions expressed on this website or platform, or during discussions and presentations (both verbal and written) are not intended as health care recommendations or medical advice by Cancer Patient Lab, its principals, presenters, participants, or representatives for any medical treatment, product, or course of action. 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. 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. (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
•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.
•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.
•Analyze cell types in tumor microenvironment using 20-30 antibody panels.
•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.
•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.
•Michael Hensley discusses using MX if to better understand why some tumors respond to immunotherapy while others do not.
•Kate's research focuses on comparing multiplex fluorescence data with bulk sequencing data to identify the biology of the tumor and why some tumor hubs do not exhaust, even with a lot of immune cells in the non-malignant component around the tumor.
•David Plunkett asks about the durability of tissue samples for analysis, with Katerina Postovalova explaining that samples older than 5 years may not be practical to use.
•Katerina Postovalova also notes that there can be significant differences between primary tumors and metastases in patients with available samples, and that some cancers are difficult to analyze due to their nature.
•Katerina Postovalova discusses the challenges of analyzing bulk RNA sequencing data from metastatic and primary tumors, including differences in tumor purity and the need for proper sample preparation.
•Katerina Postovalova also highlights the importance of considering necrotic tissue in NGS data analysis and multiplex fluorescence staining, and how it can affect the results.
•Michael Hensley discusses testing metastatic lesions to understand cancer behavior changes.
•Brian McCloskey asks about including his 7-year-old prostatectomy tissue for immune profiling, and if running both spatial and standard tests on the same tissue is possible.
•Developed algorithm to predict number of slides needed for tumor analysis, prioritizing multiplex immunofluorescence.
•Hensley discusses challenges with RNA extraction in old tissue, but successful DNA extraction can provide a comprehensive report.
•Brian McCloskey seeks advice on prioritizing tissue samples for diagnostics, given limited availability.
•Brian McCloskey and Katerina Postovalova discuss how to leverage tissue samples for personalized cancer treatment decisions, with a focus on analyzing all three time points to see the full history of tumor response.
•Michael Hensley discusses the clinical utility of immuno profiling tests, which can provide valuable insights into a patient's immune system before and after treatment.
•Brian McCloskey is considering using immuno profiling tests during his cancer treatment, and Michael Hensley offers to change the test if needed.
•Gitte Pedersen expresses interest in collaborating with the speaker's group, validating findings using I'd see, and inquires about validation of PDL one and PR two biomarkers.
•Katerina Postovalova validates PDL1 IHC slides by staining in-house and sending to external vendors for validation.
•Collaboration proposed to validate biomarkers for immunotherapy in FFPE tumor samples.
•Allen Morris hypothesizes that Gleason pattern 3 tumors are never inflamed, based on 40 years of light microscopic HIV staining.
•Allen Morris hypothesizes that immune desert in prostate cancer is actually high, backed by Provenge data.
•Katerina Postovalova mentions that their algorithm can identify immune cells in different areas of the tumor and distinguish between malignant and non- malignant cells.
•Katerina Postovalova also mentions that they have not looked at Gleason pattern 3 and stromal changes, despite Allen Morris's suggestion that this could be an important area of research.
•Rick Stanton expresses frustration with lack of access to advanced bioinformatics tools for cancer research.
•Michael Hensley emphasizes the importance of the Boston GTuner portrait test for Brian's cancer treatment.
•BostonGene's sequencing pipeline provides unique insights into tumor biology, leading to clinically actionable therapy choices.
Full transcript
Brad Power
I'm the Co-Founder and President of the Cancer Patient Lab. This is our weekly webinar series where we talk either to patients about their cases or to innovative companies, experts at the cutting edge, and then the patients do a “question and answer” to learn about whatever that area is. Today, we're honored to have Katerina Postovalova, a scientist who's working at BostonGene.
We connected initially with BostonGene through Sumit Subhudi, one of our very honored and esteemed gurus that we really listen to closely. He's an expert in immunotherapies in prostate cancer, and he described how at MD Anderson, he and others are working with BostonGene to guide their treatment decisions with patients. And so we said, “We need to make BostonGene available to the patients in our community.
I want to credit Rick Stanton with educating all of us about immunotherapies as a possible best path of treatment options because it's fighting the disease, a cancer system, with the immune system. All things being equal among your treatment options – targeted therapies, chemotherapy or radiation – if immunotherapy works, then you have a much greater chance of a durable response.
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