Cancer

Cancer Immunol Immunother (2011) 60:319–326 DOI 10.1007/s00262-010-0968-0

POSITION PAPER

2011: the immune hallmarks of cancer
Federica Cavallo • Carla De Giovanni • Patrizia Nanni • Guido Forni • Pier-Luigi Lollini

Received: 26 November 2010 / Accepted: 27 December 2010 / Published online: 26 January 2011 Ó The Author(s) 2011. This article is published with open access atSpringerlink.com

Abstract Ten years after the publication of the position paper ‘‘The hallmarks of cancer’’ (Hanahan and Weinberg Cell 100:57–70, 2000), it has become increasingly clear that mutated cells on their way to giving rise to a tumor have also to learn how to thrive in a chronically inflamed microenvironment, evade immune recognition, and suppress immune reactivity. Genetic and molecular definitionof these three immune hallmarks of cancer offers the opportunity to learn how to deploy specific countermeasures to reverse the situation in favor of the immune system and, eventually, the patient. This new information could be channeled to address what seem to be the three major hallmarks for the immune control of cancer progression: effective procedures to activate immune reactivity;characterization of not-disposable oncoantigens; and counteraction of immune suppression. Keywords Cancer Á Inflammation Á Immune surveillance Á Immune suppression Á Oncoantigens Á Tumor vaccine Á Antitumor antibodies
F. Cavallo (&) Á G. Forni Department of Clinical and Biological Sciences, University of Turin, Molecular Biotechnology Center, Via Nizza 52, 10126 Turin, Italy e-mail: federica.cavallo@unito.itC. De Giovanni Á P. Nanni Department of Experimental Pathology, Alma Mater Studiorum University of Bologna, Cancer Research Section, Viale Filopanti 22, 40126 Bologna, Italy P.-L. Lollini Department of Hematology and Oncologic Sciences ‘‘L. & A. Seragnoli’’, Alma Mater Studiorum University of Bologna, Cancer Research Section, Viale Filopanti 22, 40126 Bologna, Italy

The immune hallmarks ofcancer In an important position paper published in January 2000, Hanahan and Weinberg listed six alterations essential for malignant growth: self-sufficiency in growth signals, insensitivity to antigrowth signals, limitless replicative potential, ability to evade apoptosis, sustained angiogenesis, and ability to invade the tissues and metastasize [1]. The ability to deal with immune mechanisms, however,was not included among these essential capabilities, but may be supposed to be acquired by most—and perhaps all—tumors. Because of the authoritative impact of this paper, these six hallmarks are usually quoted as the starting ground for new anticancer strategies, while the addition of other critical features of malignant tumors as hallmarks is often urged [2]. In the 10 years since thepublication of the paper, it has become increasingly clear that both exploitation of immune mechanisms and evasion of immune surveillance are skills that cancer cells should acquire on their way to giving rise to a tumor. A comprehensive cellular, molecular, and genetic interpretation of the initially somewhat fuzzy evidence of the importance of such acquisition has also been worked out. Three such immunehallmarks are certainly required: 1. 2. 3. Ability to thrive in a chronically microenvironment Ability to evade immune recognition Ability to suppress immune reactivity inflamed

These three capabilities and acquisition of the genetic changes required to put them into practice are constant and essential features of natural and experimental cancers. Their strength, however, may vary from one kindof tumor to another, and even more variable are the mechanisms

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Cancer Immunol Immunother (2011) 60:319–326

through which the various types of cancer undertake these activities. Acquisition of a specific genome change, therefore, is not important, whereas acquisition of these capabilities is crucial, irrespective of the mechanisms involved. Ability to thrive in a chronically...