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      Cancer Immunoediting: Integrating Immunity’s Roles in Cancer Suppression and Promotion

      Author(s): 1 , 2 , 3 , 4
      Publication date Created:
      Publication date (Print):
      Journal: Science
      Publisher: American Association for the Advancement of Science (AAAS)

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          Abstract

          Understanding how the immune system affects cancer development and progression has been one of the most challenging questions in immunology. Research over the past two decades has helped explain why the answer to this question has evaded us for so long. We now appreciate that the immune system plays a dual role in cancer: It can not only suppress tumor growth by destroying cancer cells or inhibiting their outgrowth but also promote tumor progression either by selecting for tumor cells that are more fit to survive in an immunocompetent host or by establishing conditions within the tumor microenvironment that facilitate tumor outgrowth. Here, we discuss a unifying conceptual framework called “cancer immunoediting,” which integrates the immune system’s dual host-protective and tumor-promoting roles.

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          The Hallmarks of Cancer

          Douglas Hanahan, Robert Weinberg (2000)
          Article 0 comments Cited 2265 times – based on 0 reviews     Review now
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            Improved Survival with Ipilimumab in Patients with Metastatic Melanoma

            F. Stephen Hodi, Steven J O'Day, David F McDermott … (2010)
            An improvement in overall survival among patients with metastatic melanoma has been an elusive goal. In this phase 3 study, ipilimumab--which blocks cytotoxic T-lymphocyte-associated antigen 4 to potentiate an antitumor T-cell response--administered with or without a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone in patients with previously treated metastatic melanoma. A total of 676 HLA-A*0201-positive patients with unresectable stage III or IV melanoma, whose disease had progressed while they were receiving therapy for metastatic disease, were randomly assigned, in a 3:1:1 ratio, to receive ipilimumab plus gp100 (403 patients), ipilimumab alone (137), or gp100 alone (136). Ipilimumab, at a dose of 3 mg per kilogram of body weight, was administered with or without gp100 every 3 weeks for up to four treatments (induction). Eligible patients could receive reinduction therapy. The primary end point was overall survival. The median overall survival was 10.0 months among patients receiving ipilimumab plus gp100, as compared with 6.4 months among patients receiving gp100 alone (hazard ratio for death, 0.68; P<0.001). The median overall survival with ipilimumab alone was 10.1 months (hazard ratio for death in the comparison with gp100 alone, 0.66; P=0.003). No difference in overall survival was detected between the ipilimumab groups (hazard ratio with ipilimumab plus gp100, 1.04; P=0.76). Grade 3 or 4 immune-related adverse events occurred in 10 to 15% of patients treated with ipilimumab and in 3% treated with gp100 alone. There were 14 deaths related to the study drugs (2.1%), and 7 were associated with immune-related adverse events. Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma. Adverse events can be severe, long-lasting, or both, but most are reversible with appropriate treatment. (Funded by Medarex and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00094653.)
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              Immunity, inflammation, and cancer.

              Sergei I. Grivennikov, Florian Greten, Michael Karin (2010)
              Inflammatory responses play decisive roles at different stages of tumor development, including initiation, promotion, malignant conversion, invasion, and metastasis. Inflammation also affects immune surveillance and responses to therapy. Immune cells that infiltrate tumors engage in an extensive and dynamic crosstalk with cancer cells, and some of the molecular events that mediate this dialog have been revealed. This review outlines the principal mechanisms that govern the effects of inflammation and immunity on tumor development and discusses attractive new targets for cancer therapy and prevention. 2010 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Title: Science
                Abbreviated Title: Science
                Publisher: American Association for the Advancement of Science (AAAS)
                ISSN (Print): 0036-8075
                ISSN (Electronic): 1095-9203
                Publication date Created: March 25 2011
                Publication date (Print): March 25 2011
                Volume: 331
                Issue: 6024
                Pages: 1565-1570
                Affiliations
                [1 ]Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
                [2 ]New York Branch of The Ludwig Institute for Cancer Research at Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
                [3 ]Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, 3002 Victoria, Australia.
                [4 ]Department of Pathology, University of Melbourne, Parkville, 3010 Victoria, Australia.
                Article
                DOI: 10.1126/science.1203486
                SO-VID: de4c8e60-b28e-403b-9523-af4e6a095639
                Copyright © © 2011
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