Expression of Cancer Testis (CT) Antigens in Thymus of the Fetus
Achim A Jungbluth, Denise Frosina, Megan Holz, Sacha Gnjatic, Giulio C Spagnoli, Annette M Mueller. Ludwig Institute for Cancer Research, New York, NY; University Hospital, Basel, Switzerland; University Hospital, Bonn, Germany
Background: CT antigens such as NY-ESO-1, MAGE, GAGE, and CT7 are named after their characteristic pattern of expression, since they are found in various types of cancer and in normal adult tissues solely present in testicular germ cells. They are also present in fetal ovarian germ cells and occasionally in placenta. In cancer patients, some CT antigens are highly immunogenic and due to their limited expression in normal tissues, are used as vaccine targets for cancer immunotherapy. They also serve as markers of malignancy. Little is known about the biology of CT antigens and especially their role in the normal immune system. Consequently, here was analyzed the presence of CT antigens in a series of fetal thymic tissues.
Design: Archival thymus tissue from 40 fetuses (week 15-42) was available for analysis. IHC using the following mAbs (to the following CT antigens) were used: MA454 (MAGE-A1), 57B (MAGE-A4), E978 (NY-ESO-1), #26 (GAGE), CT7-33 (CT7), and CT10#5 (CT10).
Results: Expression of CT antigens in thymus was highly variable. NY-ESO-1 remained completely negative. MAGE-A1 was present in single cells of only three cases. CT7 and CT10 were present in 10 and 11 thymi respectively, both showing solely focal staining. GAGE and MAGE-A4 were most abundantly expressed: GAGE was present in 22/40 and MAGE-A4 in 27/40 tissues; both antigens displayed large groups of positive cells. For all tested antigens, immunopositive cells were restricted to the medulla and were exclusively epithelial cells. There was not predilection of any gestational age for any of the tested antigens.
Conclusions: The present study shows that -irrespective of fetal age- several CT antigens are consistently present in fetal thymus, albeit to a variable degree. Expression is restricted to thymus epithelial cells and ranges from a few cells to larger groups of cells; GAGE and MAGE-A4 are most abundantly present. Interestingly, there was no NY-ESO-1 expression in any of the tested thymi. These data complement serological data in cancer patients which show rare immune responses to those antigens, which were highly expressed in our series of thymus tissues. NY-ESO-1, however, is the most immunogenic antigen in cancer patients. The lack of NY-ESO-1 expression in fetal thymus could be the cause of lacking pre-existing immunotolerance to NY-ESO-1 rendering cancer patients more sensitive to the presence of NY-ESO-1 in cancer tissue and consequently to vaccine applications.
Monday, March 4, 2013 1:00 PM
Poster Session II # 273, Monday Afternoon