Cyclin B1 and Other Cyclins as Tumor Antigens in Immunosurveillance and Immunotherapy of Cancer

Abstract

Uncontrolled cell division is an indispensable event in tumor progression, and numerous molecules involved in this process have been the focus of intense investigation in tumor biology. Cyclins, molecules that orchestrate normal cell cycle progression, are abnormally overexpressed in various human cancers. We review evidence that the immune system recognizes some abnormally expressed cyclins as tumor antigens, such as cyclin B1, and we analyze the potential of cyclins D, E, and A to serve a similar function in cancer immunosurveillance. (Cancer Res 2006; 66(1): 6-9)

Identification of Distinct Gene Expression Profiles between Esophageal Squamous Cell Carcinoma and Adjacent Normal Epithelial Tissues

“…Disruption of this equilibrium by loss of cell cycle control may eventually lead to tumor development (Sandal 2002). It has been well known that cyclins, a family of proteins that control cell cycle progression in cells, are abnormally overexpressed in various human cancers (Egloff et al 2006). In the present study, we detected several cell cycle regulators that were up-regulated markedly in ESCC tissues compared with normal esophageal mucosae, including cyclin B1, cyclin A2, cyclin F, cell division cycle 2 (CDC2), CDC28 protein kinase regulatory subunit 1B (CKS1B) and CDC28 protein kinase regulatory subunit 2 (CKS2).…”

Helicobacterpylori-induced modification of the histone H3 phosphorylation status in gastric epithelial cells reflects its impact on cell cycle regulation

“…On completion of DNA synthesis, the phosphatase CDC25C renders the complex active at the G 2 /M boundary, which subsequently leads to nuclear translocation of the cyclin B1/CDC2 complex in early M-phase. 26 The accumulation of cyclin B1 in the cytoplasm points towards a H. pylori-induced G 2 arrest. One reason for the non-initiation of cyclin B1/CDC2 is the effect of H. pylori on CDC25C: transcript and protein levels of this phosphatase are strongly diminished at the same post-infection time as the observed cyctoplasmic cyclin B1 accumulation.…”

The shared tumor associated antigen cyclin‐A2 is recognized by high‐avidity T‐cells

“…32,36 In view of these encouraging results, an increasing number of studies is currently addressing the role of the cyclins as tumor antigens in immuno surveillance and immunotherapy. 2 We conclude that the induction of MHC-restricted CTL specific for the peptide CA213is feasible and that such CTL can recognize endogenously expressed antigen on tumor cells. Cyclin-A2 is an attractive candidate for immune intervention in a significant number of cancer patients.…”

“…1 Several cyclin genes have been shown to be overexpressed in cancer and cell cycle regulators have been suggested as potential targets of antitumor immune intervention. [2][3][4][5] Cyclin-A2 is a key regulatory protein of the cell cycle. In mammalian cells, it is involved in the control of the G2/M cell cycle transition and S-phase progression through its association with distinct cyclin-dependent kinases.…”