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Toward integrative cancer immunotherapy: targeting the tumor microenvironment

Leisha A Emens1122*, Samuel C Silverstein34, Samir Khleif5, Francesco M Marincola67 and Jérôme Galon101189

Author Affiliations

1 Tumor Immunology and Breast Cancer Research Programs, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA

2 Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA

3 Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA

4 Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA

5 Georgia Health Sciences University (GHSU) Cancer Center, Georgia, USA

6 Infectious Diseases and Immunogenetics Section (IDIS), National Institutes of Health, Bethesda, MD 20891, USA

7 Department of Transfusion Medicine, Clinical Center and trans-NIH Center for Human Immunology (CHI), National Institutes of Health, Bethesda, MD 20891, USA

8 INSERM, UMRS872, Cordeliers Research Centre, Laboratory of Integrative Cancer Immunology, Paris F-75006, France

9 Assistance Publique-Hopitaux de Paris, AP-HP, Georges Pompidou European Hospital, Paris, France

10 Université Paris Descartes, Paris, France

11 Université Pierre et Marie Curie Paris 6, Paris, France

12 The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University, 1650 Orleans Street, Room 409, Bunting Blaustein Cancer Research Building, Baltimore, MD 21231-1000, USA

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Journal of Translational Medicine 2012, 10:70  doi:10.1186/1479-5876-10-70

Published: 10 April 2012


The development of cancer has historically been attributed to genomic alterations of normal host cells. Accordingly, the aim of most traditional cancer therapies has been to destroy the transformed cells themselves. There is now widespread appreciation that the progressive growth and metastatic spread of cancer cells requires the cooperation of normal host cells (endothelial cells, fibroblasts, other mesenchymal cells, and immune cells), both local to, and at sites distant from, the site at which malignant transformation occurs. It is the balance of these cellular interactions that both determines the natural history of the cancer, and influences its response to therapy. This active tumor-host dynamic has stimulated interest in the tumor microenvironment as a key target for both cancer diagnosis and therapy. Recent data has demonstrated both that the presence of CD8+ T cells within a tumor is associated with a good prognosis, and that the eradication of all malignantly transformed cells within a tumor requires that the intra-tumoral concentration of cytolytically active CD8+ effector T cells remain above a critical concentration until every tumor cell has been killed. These findings have stimulated two initiatives in the field of cancer immunotherapy that focus on the tumor microenvironment. The first is the development of the immune score as part of the routine diagnostic and prognostic evaluation of human cancers, and the second is the development of combinatorial immune-based therapies that reduce tumor-associated immune suppression to unleash pre-existing or therapeutically-induced tumor immunity. In support of these efforts, the Society for the Immunotherapy of Cancer (SITC) is sponsoring a workshop entitled "Focus on the Target: The Tumor Microenvironment" to be held October 24-25, 2012 in Bethesda, Maryland. This meeting should support development of the immune score, and result in a position paper highlighting opportunities for the development of integrative cancer immunotherapies that sculpt the tumor microenvironment to promote definitive tumor rejection.