Key words CT antigens; immunotherapy; nervous system tumors

    Nervous system tumors, although the incidence is not high, but the death, disability is very high. Higher recurrence rate of traditional therapies. Therefore, the need to explore new treatments to improve the efficacy of the combination with traditional therapies. Immunotherapy invasive, targeted and concern. However, the obtaining of the tumor-specific antigen is the premise of immunotherapy. Specific antigen, present in the tumors of the nervous system is very small, so the application role is a relatively wide range of cancer  testis antigen (Cancer  Testis Antigen, CT antigen) in the treatment of nervous system tumor development prospects. Great progress in recent years in the study of nervous system tumors in CT antigens, now Research Development of CT antigen in tumors of the nervous system are as follows:

    1 CT antigen Overview

    1.1 CT antigen gene function

    CT antigens are a class can be expressed in a variety of tumor tissue and almost no expression in normal tissues except testis outside antigen [1]. 96 CT antigen gene has now been found, respectively, by the 15 gene family, and the 31 kinds of genes encoding. According to the CT antigen localization is on the X chromosome, the CT antigen gene is divided into two categories: (1) X  CT antigen gene: located on the X chromosome, concentrated in the Xp11 and Xq26 ~ 28 two regions, such gene basically a multi-gene family, including MAGE, GAGE, NY  ESO  1, SSX, XAGE, SPANX as well as a newly discovered CT45, etc. [1  3] 20 genes or gene families. (2) NonX  CT antigen gene: positioning on different autosomal of the SCP  1, CT9, CT46 positioned on chromosome 1, OY  TES  1 positioning on the 12th chromosome finest [1,4  6 ], non-familial genes.

    CT antigen function is also very little, only to understand the function of a few CT antigens. Institute of known to the CAGE  1 as an important part of the sperm cell and the sperm acrosome, the packaging of the sperm acrosome protein plays an important role [3]; SCP  1 as the main component of the synaptonemal complex and chromosome pairing, exchange and separation of closely related [7]; the SSX gene may be associated with the inhibition of transcription [8].

    1.2 CT antigen expression characteristics and mechanisms

    While the discovery of the first CT antigen derived from melanoma, but subsequent studies found that the the CT antigen actually is a broad spectrum of tumor antigens, the expression of it in a variety of tumor tissue is different. Generally speaking, the expression of CT antigens in tumor tissue has the following characteristics: (1) the same CT antigens different in the frequency of different tumor tissues; (2) of CT antigen expression frequency of the same tumor tissue also different; (3) CT antigen expression has a “cluster" of that same tumor tissue can express a variety of CT antigen.

    CT antigen expression mechanism has not yet been fully elucidated. The major research focus on the MAGE family, some scholars have reported vitro demethylating by induction agent 5-AZA the  CdR, can induce a variety of tumor cells and normal cells expressing MAGE gene [9]. However, demethylation mechanism does not explain the mechanism of all CT antigen expression. Studies have found that in the genome widely demethylation colon, many CT antigens absence [10]. Therefore, CT antigen-specific expression in addition to the mechanism of induction of demethylation, it may still be associated with other mechanisms in the tumor-specific expression mechanism needs further study and proof.

    2 nervous system tumors with CT antigen

    CT antigen expression in the nervous system tumor less, only several CT antigens, MAGE and other family related reports, now the progress of their research are described below:

    2.1 MAGE family

    MAGE genes in tumors of the nervous system in mRNA levels reported more. Studied types of nervous system tumors, including malignant glioma, neuroblastoma cell tumors, meningioma and medulloblastoma tumors, etc., the expression rate of 5% to 66% range [11  17]. MAGE  1 expression in neuroblastoma highest rate (66%), it is worth noting that MAGE  1 expression rate of malignant glioma in adults and children have significantly different. , MAGE gene expression of protein levels in the tumor tissue of the nervous system have been reported, the expression rate of MAGE protein levels in the tumors of the nervous system ranging from 35.7% to 85.7% [12, 16, 18] to MAGE  1 the highest rate of protein expression in glioma.

    Although the study results show that, regardless of MAGE genes at the mRNA and protein levels in tumor tissues, MAGE expression, there are differences, but overall, some members of the MAGE gene family in specific tumors of the nervous system in higher expression, therefore, is expected to become the nervous system tumor immunotherapy targeting.

    2.2 NY  ESO  1

    NY  ESO  1 expression of mRNA levels in the tumors of the nervous system, Soling, [13] by RT  PCR detected 88 cases of brain tumors, including astrocytomas, between glioma, meningioma ependymoma, but have not found one case of NY of  ESO  1 expression. Is to apply the same method to detect neuroblastoma, NY  ESO  1 expression was ranging from 25% to 55% [13,16,19]. And the study of the protein level, Rodolfo, etc. [19] the use of immunohistochemical techniques to analyze neuroblastoma specimens NY  ESO  1 protein expression was 82%, the immune response can be found in most of the tumor cells in the specimen .

    This suggests that neuroblastoma NY  ESO  1 expression at the mRNA and protein levels higher and more research results show that the strong immunogenicity of the antigen NY  ESO  1 [20], therefore, NY  ESO  1 in neuroblastoma tumor immunotherapy has broad prospects.

    2.3 NY  SAR  35

    Recently our group [21] NY  SAR  35 expression in meningiomas study, found its expression in meningiomas was 36.59%, significantly higher than normal tissue expression rate of 13.79%, and Statistics analysis of NY  SAR  35 expression and patient gender, age, type of tumor and tumor grade.

    2.4 SSX family

    At present, confirmed at the mRNA level research the SSX family expression in tumors of the nervous system rate ranging from 5% to 72% [17, 22]. Highest expression in neuroblastoma, astrocytoma and glioma expression rate is relatively low. Among them SSX  2 was the highest expression in neuroblastoma. SSX gene expression of protein levels in the nervous system tumor No reports, but along with the SSX antibody commercialization, will be updated research progress.

    It can be seen that the SSX family with NY  ESO  1 in conjunction neuroblastoma immunotherapy target antigen.

    2.5 GAGE ​​family

    For a the CAGE family in the study of nervous system tumors, mostly at the mRNA level. Scarcella [11] detected GAGE ​​expression in 60 cases of nervous system tumors. The results showed that the GAGE ​​family expression at the mRNA level was 11% to 93% range to take advantage of the universal primers amplified the GAGE ​​ common sequence of GAGE ​​ 6 GAGE ​​ 8 mRNA in ventricle ependymoma Expression highest rate. Is MAGE different, found no differences in the rate of adults and children expression in malignant glioma. Addition, Cheung et al [23] found that 82% of the rate of GAGE ​​expression in 67 cases of neuroblastoma tissue. It can be seen GAGE ​​family expression in certain nervous system tumors, may be an ideal target as these nervous system tumor immunotherapy.

    2.6 SCP  1

    Sahin [17] by RT  PCR technology to detect 39 cases of astrocytoma and 38 cases of meningioma, SCP  1 expression rate of 40% and 18%, respectively. This prompted SCP  1 expression tend to malignant tumors still needs further study.

    2.7 CT46

    Chen et al [4] The application of quantitative RT  PCR technology found CT46 expression in neuroblastoma cell lines, however, due to fewer present their research, not yet determine CT46 expression in other nervous system tumors Therefore, pending further study.

    3 application of CT antigens on the outlook for the treatment of nervous system tumors

    The CT antigens immunotherapy has been carried out in non-nervous system tumors. CT antigen in tumors of the nervous system have also been progress, Liu et al [12] found that MAGE  1 expression in malignant glioma and cytotoxic T cell recognition. IFN  γ or the 5  AZA  CdR role in glioblastoma, MAGE mRNA expression rate can be significantly improved, and can promote self MHC antigen epitopes revealed, thus improving the recognition activity of cytotoxic T lymphocytes. This indicates that the MAGE  1 as a specific target antigens of malignant glioma, which applied to the active immunotherapy of malignant glioma, CD4, CD8 T cell dependence and adoptive immunotherapy. But the application of CT antigen immunotherapy of tumors of the nervous system has not been extensively developed, and constraints that carried out one of the important factors is the CT antigen expression profiles of tumors of the nervous system is not very clear.

    4 Conclusion

    Studies have confirmed part of CT antigen expression in tumors of the nervous system, but the expression of a relatively low rate. The future, on the one hand the need to continue looking for more highly expressed in the nervous system tumors, CT antigens; the other hand, need for extensive screening known CT antigen, from which to obtain a more complete expression of CT antigens spectrum. With the establishment of the CT antigen expression profiling of tumors of the nervous system, the CT antigen targeting, immunotherapy of tumors of the nervous system is bound to become possible.