CT45, an Unexpected Link Between Hodgkin Lymphoma and Reproductive Germ Cells

Hodgkin lymphoma, a distinctive group of malignant lymphoma first described by Thomas Hodgkin in 1832, remains mysterious in many aspects today, more than 175 years since its initial description. Unlike most lymphomas, where the affected lymphoid organs are overtaken by sheets of tumor cells, the malignant cells in Hodgkin lymphoma often exist as individual giant cells in solitude, interspersed in between numerous benign small lymphocytes.

The origin of these neoplastic giant cells, called Reed-Sternberg cells, and how they have attracted their accompanying benign lymphocytes, have baffled scientists and hematologists for many decades. These malignant cells are now considered to be derived from B lymphocytes, and yet they do not express many molecules that are found in most B lymphocytes, and doubts remain about the true origin of these malignant cells.

In a paper published in the Proceedings of the National Academy of Sciences (PNAS) earlier this month, the laboratory of Dr. Lloyd J. Old of the Ludwig Institute for Cancer Research (LICR), together with Dr. Yao-Tseng Chen at Weill Cornell Medical College and their collaborators, made the finding that CT45, a cancer/testis (CT) antigen normally expressed in testicular germ cells in both prenatal and adult life, is expressed by the Reed-Sternberg cells in most of the classical Hodgkin lymphomas.

CT antigen was a term coined by Old and Chen in 1996 to describe an unusual group of germ cell antigens that they and others had discovered in their quest for tumor antigens for cancer immunotherapy. This group of antigens is normally silenced in all other normal cells in adult, and yet is aberrantly activated and expressed in a subset of various human cancers, often eliciting immune response in cancer patients.

Chen and Old discovered CT45 in 2005 and went on to show that CT45 is expressed in many cancers, notably in ovarian cancer and lung cancer. In contrast to the expression of CT45 in these epithelial cancers, they described in the current paper that CT45 expression in Hodgkin lymphoma is much more frequent, particularly when compared to other CT antigens, which are expressed in 0-25% in Hodgkin lymphoma. This high frequency of strong expression of CT45 in Hodgkin lymphoma indicates that CT45 could be a cancer vaccine target for Hodgkin lymphoma and related grey-zone lymphoma—lymphomas that bear the characteristics of both classic Hodgkin lymphoma as well as diffuse large B cell lymphoma, or non-Hodgkin lymphoma.

Even more intriguing, this finding points to a link between the malignant transformation in Hodgkin lymphoma and the process of germ cell development. These findings strengthen the theory that CT-coding genes that are active at the earliest stages of life, silenced in normal adult tissue, and then re-expressed in cancer, are major contributors to the abnormal growth and invasive properties of cancer.

Reference Publication
Chen YT et al. Expression of cancer testes antigen CT45 in classical Hodgkin lymphoma and other B-cell lymphomas. Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3093-8. Epub 2010 Jan 26.

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About the Ludwig Institute for Cancer Research (LICR) New York Branch of Human Cancer Immunology at Memorial Sloan-Kettering Cancer Center (MSKCC). The New York Branch of Human Cancer Immunology at Memorial Sloan-Kettering Cancer Center is one of the ten research branches of the Ludwig Institute for Cancer Research, a global non-profit institute committed to improving the understanding and control of cancer through integrated laboratory and clinical discovery.

The New York Branch of Human Cancer Immunology’s main objective is the identification of suitable targets for antibody-based and vaccine-based immunotherapies of cancer. Over the years, the laboratory has defined a wide range of antibodies that target cell surface antigens on human cancer cells, as well as a range of intracellular antigens targeted by humoral and cellular immune responses. Based on detailed serological, biochemical, cellular, immunohistochemical and genetic characterization, a number of these antibodies and tumor antigens have been selected for early phase clinical trials. To learn more, visit www.licr.org.