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Emerging concepts in biomarker discovery; The US-Japan workshop on immunological molecular markers in oncology

Hideaki Tahara1*, Marimo Sato1*, Magdalena Thurin2*, Ena Wang3*, Lisa H Butterfield4*, Mary L Disis5, Bernard A Fox6, Peter P Lee7, Samir N Khleif8, Jon M Wigginton9, Stefan Ambs10, Yasunori Akutsu11, Damien Chaussabel12, Yuichiro Doki13, Oleg Eremin14, Wolf Hervé Fridman15, Yoshihiko Hirohashi16, Kohzoh Imai16, James Jacobson2, Masahisa Jinushi1, Akira Kanamoto1, Mohammed Kashani-Sabet17, Kazunori Kato18, Yutaka Kawakami19, John M Kirkwood4, Thomas O Kleen20, Paul V Lehmann20, Lance Liotta21, Michael T Lotze22, Michele Maio2324, Anatoli Malyguine25, Giuseppe Masucci26, Hisahiro Matsubara11, Shawmarie Mayrand-Chung27, Kiminori Nakamura18, Hiroyoshi Nishikawa28, A Karolina Palucka12, Emanuel F Petricoin21, Zoltan Pos3, Antoni Ribas29, Licia Rivoltini30, Noriyuki Sato31, Hiroshi Shiku28, Craig L Slingluff32, Howard Streicher33, David F Stroncek34, Hiroya Takeuchi35, Minoru Toyota36, Hisashi Wada13, Xifeng Wu37, Julia Wulfkuhle21, Tomonori Yaguchi19, Benjamin Zeskind38, Yingdong Zhao39, Mai-Britt Zocca40 and Francesco M Marincola3*

Author Affiliations

1 Department of Surgery and Bioengineering, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan

2 Cancer Diagnosis Program, National Cancer Institute (NCI), National Institutes of Health (NIH), Rockville, Maryland, 20852, USA

3 Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center and Center for Human Immunology (CHI), NIH, Bethesda, Maryland, 20892, USA

4 Departments of Medicine, Surgery and Immunology, Division of Hematology Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, 15213, USA

5 Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington, Seattle, Washington, 98195, USA

6 Earle A Chiles Research Institute, Robert W Franz Research Center, Providence Portland Medical Center, and Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon, 97213, USA

7 Department of Medicine, Division of Hematology, Stanford University, Stanford, California, 94305, USA

8 Cancer Vaccine Section, NCI, NIH, Bethesda, Maryland, 20892, USA

9 Discovery Medicine-Oncology, Bristol-Myers Squibb Inc., Princeton, New Jersey, USA

10 Laboratory of Human Carcinogenesis, Center of Cancer Research, NCI, NIH, Bethesda, Maryland, 20892, USA

11 Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan

12 Baylor Institute for Immunology Research and Baylor Research Institute, Dallas, Texas, 75204, USA

13 Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan

14 Section of Surgery, Biomedical Research Unit, Nottingham Digestive Disease Centre, University of Nottingham, NG7 2UH, UK

15 Centre de la Reserche des Cordeliers, INSERM, Paris Descarte University, 75270 Paris, France

16 Sapporo Medical University, School of Medicine, Sapporo, Japan

17 Melanoma Clinic, University of California, San Francisco, California, USA

18 Department of Molecular Medicine, Sapporo Medical University, School of Medicine, Sapporo, Japan

19 Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan

20 Cellular Technology Ltd, Shaker Heights, Ohio, 44122, USA

21 Department of Molecular Pathology and Microbiology, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, Virginia, 10900, USA

22 Illman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, 15213, USA

23 Medical Oncology and Immunotherapy, Department. of Oncology, University, Hospital of Siena, Istituto Toscano Tumori, Siena, Italy

24 Cancer Bioimmunotherapy Unit, Department of Medical Oncology, Centro di Riferimento Oncologico, IRCCS, Aviano, 53100, Italy

25 Laboratory of Cell Mediated Immunity, SAIC-Frederick, Inc. NCI-Frederick, Frederick, Maryland, 21702, USA

26 Department of Oncology-Pathology, Karolinska Institute, Stockholm, 171 76, Sweden

27 The Biomarkers Consortium (BC), Public-Private Partnership Program, Office of the Director, NIH, Bethesda, Maryland, 20892, USA

28 Department of Cancer Vaccine, Department of Immuno-gene Therapy, Mie University Graduate School of Medicine, Mie, Japan

29 Department of Medicine, Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California, 90095, USA

30 Unit of Immunotherapy of Human Tumors, IRCCS Foundation, Istituto Nazionale Tumori, Milan, 20100, Italy

31 Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan

32 Department of Surgery, Division of Surgical Oncology, University of Virginia School of Medicine, Charlottesville, Virginia, 22908, USA

33 Cancer Therapy Evaluation Program, DCTD, NCI, NIH, Rockville, Maryland, 20892, USA

34 Cell Therapy Section (CTS), Department of Transfusion Medicine, Clinical Center, NIH, Bethesda, Maryland, 20892, USA

35 Department of Surgery, Keio University School of Medicine, Tokyo, Japan

36 Department of Biochemistry, Sapporo Medical University, School of Medicine, Sapporo, Japan

37 Department of Epidemiology, University of Texas, MD Anderson Cancer Center, Houston, Texas, 77030, USA

38 Immuneering Corporation, Boston, Massachusetts, 02215, USA

39 Biometric Research Branch, NCI, NIH, Bethesda, Maryland, 20892, USA

40 DanDritt Biotech A/S, Copenhagen, 2100, Denmark

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Journal of Translational Medicine 2009, 7:45  doi:10.1186/1479-5876-7-45

Published: 17 June 2009


Supported by the Office of International Affairs, National Cancer Institute (NCI), the "US-Japan Workshop on Immunological Biomarkers in Oncology" was held in March 2009. The workshop was related to a task force launched by the International Society for the Biological Therapy of Cancer (iSBTc) and the United States Food and Drug Administration (FDA) to identify strategies for biomarker discovery and validation in the field of biotherapy. The effort will culminate on October 28th 2009 in the "iSBTc-FDA-NCI Workshop on Prognostic and Predictive Immunologic Biomarkers in Cancer", which will be held in Washington DC in association with the Annual Meeting. The purposes of the US-Japan workshop were a) to discuss novel approaches to enhance the discovery of predictive and/or prognostic markers in cancer immunotherapy; b) to define the state of the science in biomarker discovery and validation. The participation of Japanese and US scientists provided the opportunity to identify shared or discordant themes across the distinct immune genetic background and the diverse prevalence of disease between the two Nations.

Converging concepts were identified: enhanced knowledge of interferon-related pathways was found to be central to the understanding of immune-mediated tissue-specific destruction (TSD) of which tumor rejection is a representative facet. Although the expression of interferon-stimulated genes (ISGs) likely mediates the inflammatory process leading to tumor rejection, it is insufficient by itself and the associated mechanisms need to be identified. It is likely that adaptive immune responses play a broader role in tumor rejection than those strictly related to their antigen-specificity; likely, their primary role is to trigger an acute and tissue-specific inflammatory response at the tumor site that leads to rejection upon recruitment of additional innate and adaptive immune mechanisms.

Other candidate systemic and/or tissue-specific biomarkers were recognized that might be added to the list of known entities applicable in immunotherapy trials. The need for a systematic approach to biomarker discovery that takes advantage of powerful high-throughput technologies was recognized; it was clear from the current state of the science that immunotherapy is still in a discovery phase and only a few of the current biomarkers warrant extensive validation. It was, finally, clear that, while current technologies have almost limitless potential, inadequate study design, limited standardization and cross-validation among laboratories and suboptimal comparability of data remain major road blocks. The institution of an interactive consortium for high throughput molecular monitoring of clinical trials with voluntary participation might provide cost-effective solutions.