Cambridge Healthtech Institute 第2回

Immuno-Oncology Biomarkers 1: Quantitative Immune Profiling and Immune Monitoring

( がん免疫療法のバイオマーカー1:定量的免疫プロファイリングと免疫モニタリング )

2018年8月27日~28日

がん免疫療法に対応するバイオマーカーを同定するための定量的免疫プロファイリングと免疫モニタリングをテーマにしたこのカンファレンスプログラムでは、免疫系の状態を評価し、腫瘍の微小環境と末梢血のプロファイリングを行い、腫瘍の遺伝子変異負荷の判定とネオエピトープのプロファイリングを行い、予測バイオマーカーと反応バイオマーカーを開発するための定量的なアプローチが紹介されます。


Final Agenda

8月27日 (月)

7:30 am Registration & Morning Coffee

精密がん免疫療法のための腫瘍微小環境のプロファイリング

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 inhibitors.

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 Center

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

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 Presentation to be Announced


Personalis12:00
pm Luncheon Presentation: Overcoming the Obstacles of Neoantigen Detection for Cancer Vaccine Development

Kedar Hastak, PhD, Field Applications Scientist, Personalis, Inc.

Conventional exome assays often have gaps in sequencing coverage, leading to missed neoantigens. Personalis developed the ACE ImmunoID platform to overcome this and other challenges for more comprehensive neoantigen identification. ACE ImmunoID combines augmented exome/transcriptome assays with state-of-the-art bioinformatics, optimized sample preparation, and automated processes to accelerate personalized cancer vaccine development.

12:30 Session Break

免疫療法への反応に対する微生物叢の影響

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

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.

がん免疫療法に対応するリキッドバイオプシー

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 Center

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 be presented.

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

8月28日 (火)

7:30 am Morning Coffee

統合化されたバイオマーカー解析

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

10:00 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing

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 Cancer Center

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 Identification of Metabolic Biomarkers of Immunosuppressive WJMSC

Mario Jolicoeur, PhD, Professor, Chemical Engineering, Research Laboratory in Applied Metabolic Engineering, Ecole Polytechnique de Montreal

In order to assess the immunosuppressive function of a cell population, we propose to use a metabolomic approach: a kinetic model of the cell metabolism was established to identify biomarkers of immunomodulation. By describing the central metabolism as well as the main metabolic pathways involved in immunoregulation phenomena, we were able to fit our model on experimental data from strongly and poorly immunosuppressive model cells, the Wharton Jelly Mesenchymal Stromal Cells (WJMSC). Simulation results allowed to detect significant differences in their energetic state, as well as in immune-related pathways such as urea and tryptophan.

12:00 pm Close of Immuno-Oncology Biomarkers 1: Quantitative Immune Profiling and Immune Monitoring

* 不測の事態により、事前の予告なしにプログラムが変更される場合があります。

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