Epigenetic modulation of solid tumors as a novel approach for cancer immunotherapy

Emerging evidence demonstrates that epigenetic events associated with tumor development and progression may impair immunogenicity and immune recognition of cancer cells, possibly favoring their escape also from vaccination-induced antitumor immune responses. In fact, DNA hypermethylation and/or histone deacetylation plays a critical role in the downregulation and/or silencing of several genes involved in the recognition of neoplastic cells by the immune system, including human leukocyte antigens (HLAs), tumor-associated antigens, and accessory/costimulatory molecules. However, as opposed to genetic alterations, epigenetic events can be successfully handled through pharmacologic agents that induce DNA hypomethylation or inhibit histone deacetylation, resulting in a functionally "more efficient" immune profile of cancer cells. In light of the encouraging immunomodulatory results obtained with these "epigenetic drugs," they certainly will be used for the development of combined chemo-immunotherapeutic strategies for the treatment of patients with solid malignancies of different histology. © 2005 Elsevier Inc. All rights reserved.