Impact of Temozolomide on Immune Response during Malignant Glioma Chemotherapy
Malignant glioma, or glioblastoma, is the most common and lethal form of brain tumor with a median survival time of 15 months. The established therapeutic regimen includes a tripartite therapy of surgical resection followed by radiation and temozolomide (TMZ) chemotherapy, concurrently with radiatio...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Clinical and Developmental Immunology |
| Online Access: | http://dx.doi.org/10.1155/2012/831090 |
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| author | Sadhak Sengupta Jaclyn Marrinan Caroline Frishman Prakash Sampath |
| author_facet | Sadhak Sengupta Jaclyn Marrinan Caroline Frishman Prakash Sampath |
| author_sort | Sadhak Sengupta |
| collection | DOAJ |
| description | Malignant glioma, or glioblastoma, is the most common and lethal form of brain tumor with a median survival time of 15 months. The established therapeutic regimen includes a tripartite therapy of surgical resection followed by radiation and temozolomide (TMZ) chemotherapy, concurrently with radiation and then as an adjuvant. TMZ, a DNA alkylating agent, is the most successful antiglioma drug and has added several months to the life expectancy of malignant glioma patients. However, TMZ is also responsible for inducing lymphopenia and myelosuppression in malignant glioma patients undergoing chemotherapy. Although TMZ-induced lymphopenia has been attributed to facilitate antitumor vaccination studies by inducing passive immune response, in general lymphopenic conditions have been associated with poor immune surveillance leading to opportunistic infections in glioma patients, as well as disrupting active antiglioma immune response by depleting both T and NK cells. Deletion of O6-methylguanine-DNA-methyltransferase (MGMT) activity, a DNA repair enzyme, by temozolomide has been determined to be the cause of lymphopenia. Drug-resistant mutation of the MGMT protein has been shown to render chemoprotection against TMZ. The immune modulating role of TMZ during glioma chemotherapy and possible mechanisms to establish a strong TMZ-resistant immune response have been discussed. |
| format | Article |
| id | doaj-art-661014e6420744e3965c1dd30401a0a8 |
| institution | Kabale University |
| issn | 1740-2522 1740-2530 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Developmental Immunology |
| spelling | doaj-art-661014e6420744e3965c1dd30401a0a82025-02-03T05:50:21ZengWileyClinical and Developmental Immunology1740-25221740-25302012-01-01201210.1155/2012/831090831090Impact of Temozolomide on Immune Response during Malignant Glioma ChemotherapySadhak Sengupta0Jaclyn Marrinan1Caroline Frishman2Prakash Sampath3Brain Tumor Laboratory, Roger Williams Medical Center, 825 Chalkstone Avenue, Prior 222, Providence, RI 02908, USABrain Tumor Laboratory, Roger Williams Medical Center, 825 Chalkstone Avenue, Prior 222, Providence, RI 02908, USABrain Tumor Laboratory, Roger Williams Medical Center, 825 Chalkstone Avenue, Prior 222, Providence, RI 02908, USABrain Tumor Laboratory, Roger Williams Medical Center, 825 Chalkstone Avenue, Prior 222, Providence, RI 02908, USAMalignant glioma, or glioblastoma, is the most common and lethal form of brain tumor with a median survival time of 15 months. The established therapeutic regimen includes a tripartite therapy of surgical resection followed by radiation and temozolomide (TMZ) chemotherapy, concurrently with radiation and then as an adjuvant. TMZ, a DNA alkylating agent, is the most successful antiglioma drug and has added several months to the life expectancy of malignant glioma patients. However, TMZ is also responsible for inducing lymphopenia and myelosuppression in malignant glioma patients undergoing chemotherapy. Although TMZ-induced lymphopenia has been attributed to facilitate antitumor vaccination studies by inducing passive immune response, in general lymphopenic conditions have been associated with poor immune surveillance leading to opportunistic infections in glioma patients, as well as disrupting active antiglioma immune response by depleting both T and NK cells. Deletion of O6-methylguanine-DNA-methyltransferase (MGMT) activity, a DNA repair enzyme, by temozolomide has been determined to be the cause of lymphopenia. Drug-resistant mutation of the MGMT protein has been shown to render chemoprotection against TMZ. The immune modulating role of TMZ during glioma chemotherapy and possible mechanisms to establish a strong TMZ-resistant immune response have been discussed.http://dx.doi.org/10.1155/2012/831090 |
| spellingShingle | Sadhak Sengupta Jaclyn Marrinan Caroline Frishman Prakash Sampath Impact of Temozolomide on Immune Response during Malignant Glioma Chemotherapy Clinical and Developmental Immunology |
| title | Impact of Temozolomide on Immune Response during Malignant Glioma Chemotherapy |
| title_full | Impact of Temozolomide on Immune Response during Malignant Glioma Chemotherapy |
| title_fullStr | Impact of Temozolomide on Immune Response during Malignant Glioma Chemotherapy |
| title_full_unstemmed | Impact of Temozolomide on Immune Response during Malignant Glioma Chemotherapy |
| title_short | Impact of Temozolomide on Immune Response during Malignant Glioma Chemotherapy |
| title_sort | impact of temozolomide on immune response during malignant glioma chemotherapy |
| url | http://dx.doi.org/10.1155/2012/831090 |
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