Effects of concomitant temozolomide and radiation therapies on WT1-specific T-cells in malignant glioma.
OBJECTIVE
Immunotherapy targeting the Wilms' tumour 1 gene product has been proven safe and effective for treating malignant glioma in a phase II clinical study. Currently, radiation/temozolomide therapy is the standard treatment with only modest benefit. Whether combining radiation/temozolomide therapy with WT1 immunotherapy will have a negating effect on immunotherapy is still controversial because of the significant lymphocytopaenia induced by the former therapy. To address this issue, we investigated the changes in frequency and number of WT1-specific T-cells in patients with malignant gliomas.


METHODS
Twenty-two patients with newly diagnosed malignant glioma who received standard radiation/temozolomide therapy were recruited for the study. Blood samples were collected before treatment and on the sixth week of therapy. The frequencies and numbers of lymphocytes, CD8(+) T-cells, WT1-specific T-cells, regulatory T-cells, natural killer cells and natural killer T-cells were measured and analysed using T-tests.


RESULTS
Analysis of the frequency of T lymphocytes and its subpopulation showed an increase in regulatory T-cells, but no significant change was noted in the populations of T-cells, WT1-specific T-cells, NK cells and NKT cells. Reductions in the total numbers of T-cells, WT1-specific T-cells, NK cells and NKT cells were mainly a consequence of the decrease in the total lymphocyte count.


CONCLUSIONS
Radiation/temozolomide therapy did not significantly affect the frequency of WT1-specific T-cells, suggesting that the combination with WT1 immunotherapy may be possible, although further assessment in the clinical setting is warranted.
Chiba
Yasuyoshi
Y
Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Hashimoto
Naoya
N
Tsuboi
Akihiro
A
Oka
Yoshihiro
Y
Murao
Ayako
A
Kinoshita
Manabu
M
Kagawa
Naoki
N
Oji
Yusuke
Y
Hosen
Naoki
N
Nishida
Sumiyuki
S
Sugiyama
Haruo
H
Yoshimine
Toshiki
T
D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects; D001932:Brain Neoplasms / Q000276:immunology / Q000628:therapy*; D019496:Cancer Vaccines / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D005910:Glioma / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007564:Japan; D007694:Killer Cells, Natural / Q000187:drug effects / Q000528:radiation effects; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000528:radiation effects; D020266:Radiotherapy, Conformal / Q000009:adverse effects; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000528:radiation effects*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology / Q000528:radiation effects*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000528:radiation effects; D000077204:Temozolomide; D025721:WT1 Proteins / Q000276:immunology*
D018906:Antineoplastic Agents, Alkylating; D019496:Cancer Vaccines; D025721:WT1 Proteins; D003606:Dacarbazine; D000077204:Temozolomide