Cambridge Healthtech Institute’s 2nd Annual
Immuno-Oncology Biomarkers 1: Quantitative Immune Profiling and Immune Monitoring
August 27-28, 2018
Advances in immuno-oncology promise to revolutionize cancer treatment. However, many patients do not respond to immunotherapy. Immune profiling promises to identify biomarkers that predict response to immunotherapy and to help monitor its progress. Cambridge
Healthtech Institute’s Second Annual Immuno-Oncology Biomarkers 1: Quantitative Immune Profiling and Immune Monitoring meeting will cover quantitative approaches to assess the state of the immune system, profile the
tumor microenvironment and peripheral blood, determine tumor mutational burden and profile neoepitopes, and develop predictive and response biomarkers.
MONDAY, AUGUST 27
7:30 am Registration & Morning Coffee (Harbor Level)
8:25 Chairperson’s Opening Remarks
Adil Daud, MD, Professor, Hematology/Oncology, University of California, San Francisco; Director, Melanoma Clinical Research, UCSF Helen Diller Family Comprehensive Cancer Center
8:30 Insights from T Cell Profiling in the Tumor Microenvironment
Adil Daud, MD, Professor, Hematology/Oncology, University of California, San Francisco; Director, Melanoma Clinical Research,
UCSF Helen Diller Family Comprehensive Cancer Center
We will describe what we know about T cells in the tumor microenvironment and describe our research with flow cytometry of T cells in patients with melanoma and other cancers and the relationship of activated T cells and response to immune checkpoint
9:00 Precision Immunology through Deeper Single-Cell Profiling
Pratip Chattopadhyay, PhD, Associate Professor, Pathology; Director, Precision Immunology
Incubator, Isaac and Laura Perlmutter Cancer Center, New York University Langone Medical Center
In recent years, there has been a revolution in medicine’s ability to “wake up” the immune system to fight cancer. In parallel, an incredible array of new single cell technologies have been introduced to characterize immune responses.
In this talk, I will introduce two relatively new technologies - 30-parameter fluorescence flow cytometry and Integrated Molecular Cytometry Platforms (like CITE-seq) - that allow complete and comprehensive characterization of immune cells in immunotherapy
patients. I will demonstrate how we are making these technologies easier, more robust, and valuable. Finally, I will discuss some insights into the tumor-immune microenvironment.
9:30 Immune Infiltrate as a Prognostic Biomarker in Merkel Cell Carcinoma
Michael T. Tetzlaff, MD, PhD, Associate Professor, Pathology, The University of Texas MD Anderson Cancer
Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy with unpredictable response to immune checkpoint blockade. To identify prognostic/predictive immune-related biomarkers for MCC, we quantified the density and composition of the tumor associated
lymphoid infiltrate and confirmed associations with survival. Next, we performed T-cell receptor sequencing to determine associations between the T-cell repertoire and survival. Finally, we determined expression of immune checkpoint markers (beyond
PD-L1) in MCC. Our findings identify novel immune-related biomarkers in MCC.
10:00 Coffee Break (Harbor and Plaza Levels)
10:30 The Immune Microenvironment in Special Types of Pancreatic Malignancy
Elizabeth Thompson, MD, PhD, Assistant Professor, Pathology, Johns Hopkins University
The most common pancreatic malignancy, ductal adenocarcinoma, is not thought to be inherently immunogenic. However, the status of the immune response to other types of pancreatic cancer has not been explored. These tumors are difficult to treat and would
benefit from the ability to utilize treatment options like immunotherapy. This talk will explore the immune microenvironment of special subtypes of pancreatic carcinoma and evaluate their potential benefit from immunotherapy.
11:00 T Cell Repertoire Heterogeneity in Non-Small Cell Lung Cancer: Implications for Cancer Immunotherapy
Alexandre Reuben, PhD, Assistant Professor, MD Anderson Cancer Center
Responses to immunotherapy are heavily reliant on the T cell response. Here, we studied the T cell repertoire in patients with early stage non-small cell lung cancer (NSCLC). Increased intratumor T cell repertoire heterogeneity was associated with shortened
survival. Furthermore, a large proportion of T cells in NSCLC tumors were associated with factors unrelated to the tumor, such as pathogens. A greater proportion and reactivity of these T cells was also associated with shortened overall survival.
Our work sheds light on some of the challenges facing the immunotherapeutic targeting of NSCLC.
11:30 Multiplexed Immunofluorescence for Spatial Interrogation of the Tumor Microenvironment
Speaker to be Announced, PerkinElmer
Effective immunotherapy requires capturing and quantifying interactions between immune and tumor cells, best accomplished by analyzing intact tumor sections using multiplexed immunofluorescence. Existing methods, such as chromogenic IHC and flow cytometry,
cannot provide the data needed to predict responses to drugs or to detect resistance development. We report on an integrated approach that utilizes highly multiplexed, 7-color immunofluorescence labeling and image analysis to capture expression, spatial
relationships, and cellular interactions in the tumor microenvironment.
12:00 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
12:30 Session Break
1:25 Chairperson’s Remarks
Theresa Whiteside, PhD, Professor, Pathology, Immunology & Otolaryngology, Hillman Cancer Center, University of Pittsburgh School of Medicine
1:30 The Breast Tissue Microbiome: Associations with Cancer and Cancer Risk
Tina Hieken, MD, Associate Professor, Surgery, Mayo Clinic
Breast tissue contains a complex microenvironment including a mucosal immune system, providing evidence for an instrinsic breast tissue microbiome. Our pilot data from genomic analysis has confirmed the existence of a human breast tissue microbiome, distinct from that of breast skin and other microbial niches, with demonstrable differences in benign and malignant disease states. Further investigation of the microbiome of breast tissue, other body niches, and the immune microenvironment may lead to a biome-based approach to individualized breast cancer risk prediction and identify a platform for novel breast cancer prevention strategies.
2:00 Decoding Human Microbiota Metabolism and Its Role in Cancer Initiation and Treatment
Jason Crawford, PhD, Associate Professor, Chemistry and Microbial Pathogenesis, Yale University
The composition of the gut microbiota can dramatically affect cancer formation and treatment outcomes. Indeed, select members of the gut microbiota are known to promote colorectal cancer formation, whereas others are known to promote favorable environments
for cancer immunotherapies. We describe our efforts to characterize the molecular contributions of genotoxic bacteria in the gut and establish strategies to neutralize their pathways for cancer prevention. We also discuss bacterial metabolites
that stimulate the innate immune system, which could contribute to therapeutic responses.
2:30 The Gut Microbiome Influences Differential Responses to Anti-Cancer Immunotherapy
Vancheswaran Gopalakrishnan (Deepak), Post-doctoral Fellow, Laboratory
of Dr. Jennifer Wargo, Surgical Oncology – Research, UT MD Anderson Cancer Center
3:00 Breakout Discussion Groups and Refreshment Break (Harborview)
This session features discussion groups that are led by a moderator who ensures focused conversations around the key issues listed. Attendees choose to join a specific group, and the small, informal setting facilitates sharing of ideas and active
networking. Details on the topics and moderators are available on the conference website.
4:15 Tumor-Derived Exosomes as Potential Biomarkers of Cancer Progression and Immunological Dysfunction in Cancer
Theresa Whiteside, PhD, Professor, Pathology, Immunology & Otolaryngology, Hillman Cancer Center,
University of Pittsburgh School of Medicine
Plasma-derived exosomes are emerging as promising non-invasive correlates of cancer progression. In patients with solid tumors or hematological malignancies, plasma exosomes carry a cargo enriched in immunosuppressive proteins. As immune suppression
is one of the hallmarks of cancer progression, circulating exosomes rich in inhibitory molecules are implicated in mediating systemic immune suppression. The molecular cargo of plasma-derived exosomes and their effects on immune cell subsets correlate
with the disease activity and tumor stage in patients with head neck cancer (HNC) and melanoma.
4:45 FEATURED PRESENTATION: Exosomes and Their Cargo as Tumor Biomarkers
Samir Hanash, MD, PhD, Director, McCombs Institute for Cancer Early Detection and Treatment, MD Anderson Cancer
Circulating exosomes have the potential to inform about tumor status. Deep profiling of tumor derived exosomes has identified a rich cargo of antigens that induce an immune response in cancer. The contributions of exosomes in immuno-oncology will
5:15 Macrophage-Like Circulating Tumor Cells for Prognosis of Metastasis
Shulin Li, PhD, Professor, Director, Pediatric Laboratory Research Programs, W.T. and Louise Jarrett Moran Distinguished Chair, Pediatric Oncology, Pediatric Research, MD Anderson Cancer Center
CTC has been heavily investigated but metastasis associated CTCs are not clearly defined. In our recent years reports, our group has discovered cell surface vimentin (CSV) on CTC is closely associated with tumor metastasis. In this presentation, the
presenter will reveal a new subclass of CSV positive CTCs with immune cell markers—CSV-positive macrophage-like CTCs (ML-CTCs) and its correlation with metastasis in GIST.
5:45 Assessment of Immunotherapy Response via Circulating Tumor DNA
Abhijit A. Patel, MD, PhD, Associate Professor, Therapeutic Radiology, Yale University School of Medicine
Immunotherapies are known to produce slow changes in radiographic tumor size. We hypothesized that real-time measurement of tumor cell death via ctDNA could enable earlier assessment of immunotherapy response than serial CT scans in patients with
lung cancer. This presentation will summarize our findings, showing that down-trending ctDNA levels correlate strongly with radiographic response and predict a longer duration of treatment benefit, as well as superior progression-free survival
and overall survival.
6:15 End of Day
TUESDAY, AUGUST 28
7:30 am Morning Coffee (Harbor Level)
8:25 Chairperson’s Remarks
Lance D. Miller, PhD, Mary Kirkpatrick Associate Professor of Breast Cancer Research, Wake Forest Baptist Comprehensive Cancer Center
8:30 Integrative Analyses of Microbiota, Environment, and Tumor Immunity for Precision Immuno-Oncology
Shuji Ogino, MD, PhD, Chief of Program in MPE Molecular Pathological Epidemiology, Brigham and Women’s Hospital
(BWH); Professor (Pathology & Epidemiology), BWH, Dana-Farber Cancer Institute, Harvard Medical School, Harvard T.H. Chan School of Public Health; Associate Member, Broad Institute of MIT and Harvard
The integrative field of immunology-MPE (molecular pathological epidemiology) is an emerging paradigm, and can investigate influences of the exposome (dietary, lifestyle, environmental, microbial, pharmacological, and other exposures) on tumor-immune
interactions, thereby informing immunotherapy research. Using over 1000 colorectal cancer cases with rich data on immune response, whole exome sequencing (tumor and normal DNA), tumor neoantigens, and clinical outcomes, proof-of-principle immuno-MPE
studies have shown great promise for precision prevention and immuno-oncology.
9:00 Strategies for Dissecting Immunological Signatures that Can Inform Precision Therapy
Darrell R. Borger, PhD, Scientific Director, Immuno-Profiling Laboratory; Director, Translational Research/Biomarker
Laboratory, Massachusetts General Hospital Cancer Center
The targeting of immune checkpoints has been a primary focus in the treatment of cancer and has shown great efficacy. However, not all patients will similarly respond. This talk will highlight translational research efforts that combine expression
profiling with spacial analysis in patient tissue to inform combination strategies and the development of a new generation of clinical tests that have the potential to deliver precision immunotherapy.
9:30 NGS Solutions across the Oncology Drug Development Continuum: From Biomarker Discovery to IVD
John Simmons, PhD, Director, Translational Science and Diagnostics, Personal Genome Diagnostics
Biomarker-based treatment decisions have improved clinical outcomes across cancer types. Low response rates in immunotherapy highlights the need for assays to accurately predict patient response. At Personal Genome Diagnostics (PGDx), immunoncology
product portfolio centers develop assays in tissue and plasma for immunotherapies through clinical and analytical validation as in vitro diagnostics (IVDs). Our assays predict tumor mutational burden, determine microsatellite status and identify
a range of mutations in immune signaling genes.
10:00 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
10:55 Chairperson’s Remarks
Lance D. Miller, PhD, Mary Kirkpatrick Associate Professor of Breast Cancer Research, Wake Forest Baptist Comprehensive Cancer Center
11:00 Immune Gene Signature Dynamics in Breast Cancer Prognosis and Therapy Prediction
Lance D. Miller, PhD, Mary Kirkpatrick Associate Professor of Breast Cancer Research, Wake Forest Baptist Comprehensive
Gene expression signatures, common to many solid tumor types, reflect the relative abundance of tumor-infiltrating leukocyte populations. These immune gene signatures can be leveraged in large-scale tumor expression profiling studies to assess the
clinical relevance of tumor-immune interactions. In this talk, I will present evidence that breast cancer survival and treatment responses depend on the quantifiable, intratumoral interplay between cytotoxic lymphocytes, immunosuppressive myeloid
cells and tumor mutational burden.
11:30 Current Biomarkers for Cancer Immunotherapy Selection and Treatment Monitoring
Glen J. Weiss, MD, MBA, Director, Phase 1 Clinical Research, Beth Israel Deaconess Medical Center, Boston
With multiple monoclonal antibody immunotherapies available for clinical use to treat advanced cancers, and just a fraction of these patients experience an impressive durable response, how are these therapies selected and how is efficacy monitored?
The lecture will highlight current data on biomarkers being used and evaluated for treatment selection and monitoring.
12:00 pm Close of Immuno-Oncology Biomarkers 1: Quantitative Immune Profiling and Immune Monitoring