Epigenetic immunomodulation of hematopoietic malignancies.
Significant progress has been made in the clinical management of hematologic malignancies; nevertheless, a proportion of patients still remains unresponsive to available therapeutic options. Furthermore, patients who respond to specific therapeutic regimens may still require additional treatment to eradicate minimal residual disease. In this scenario, novel immunotherapeutic strategies may significantly impact on the clinical course of hematopoietic tumors in different clinical stages of disease. Among immunotherapeutic approaches under development, promising clinical results are being obtained with vaccination of patients with solid malignancies against cancer testis antigens (CTA), which belong to a growing family of methylation-regulated tumor-associated antigens (TAA) shared among human malignancies of different histologies. Based on these notions, the emerging preclinical and clinical evidence suggest that an immunomodulatory role for epigenetic drugs is highly relevant; in fact, by interfering with DNA methylation, these compounds induce or upregulate the constitutive expression of CTA on actively proliferating neoplastic cells. This novel activity of epigenetic drugs combines with their well-known cytotoxic, pro-apoptotic and differentiating activities in hematopoietic tumors that are extensively described in other chapters of this issue. This review will focus on the expression of CTA in hematopoietic malignancies, on their epigenetic regulation, and on the foreseeable immunotherapeutic implications of DNA hypometylating drugs to design new CTA-based chemo-immunotherapeutic approaches in patients with hematopoietic tumors.
Gattei
Valter
V
Clinical and Experimental Hematology Research Unit, Centro di Riferimento Oncologico, IRCCS, Aviano, Italy.
Fonsatti
Ester
E
Sigalotti
Luca
L
Degan
Massimo
M
Di Giacomo
Anna Maria
AM
Altomonte
Maresa
M
Calabrò
Luana
L
Maio
Michele
M
D000951:Antigens, Neoplasm / Q000737:chemistry; D017209:Apoptosis; D002454:Cell Differentiation; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000628:therapy; D006689:Hodgkin Disease / Q000628:therapy; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008223:Lymphoma / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy; D008565:Membrane Proteins / Q000737:chemistry; D009101:Multiple Myeloma / Q000628:therapy; D009196:Myeloproliferative Disorders / Q000628:therapy; D009369:Neoplasms / Q000188:drug therapy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D008565:Membrane Proteins