Article
Spontaneous immune responses in GBM patients after complete tumor resection are associated with an improved survival
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Authors
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Christel Herold-Mende
- Experimentelle Neurochirurgie, Neurochirurgische Universitätsklinik, Universitätsklinikum Heidelberg
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Jan Mossemann
- Experimentelle Neurochirurgie, Neurochirurgische Universitätsklinik, Universitätsklinikum Heidelberg
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Christin Dictus
- Experimentelle Neurochirurgie, Neurochirurgische Universitätsklinik, Universitätsklinikum Heidelberg
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Rezvan Ahmadi
- Experimentelle Neurochirurgie, Neurochirurgische Universitätsklinik, Universitätsklinikum Heidelberg
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Philipp Beckhove
- DKFZ Heidelberg
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Andreas Unterberg
- Experimentelle Neurochirurgie, Neurochirurgische Universitätsklinik, Universitätsklinikum Heidelberg
| Published: | May 21, 2013 |
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Outline
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Objective: In several tumor types including glioblastoma occurence of spontaneous anti-tumor immune responses have been detected. However, not only in brain tumors it is unclear if such immune responses influence the course of the disease.
Method: To detect spontaneous anti-tumor immune responses, occurence and frequencies of memory T-cells were determined in the peripheral blood applying the IFN gamma ELISPOT assay by using the autologous patient tumor (n=106) or a set of immunogenic polypeptides (n=32). Between September 2000 and April 2009 138 GBM patients were enrolled in this study. IDH1-mutated tumors and glioblastomas with oligendendroglial components were excluded. Extent of resection was assessed by early postoperative MRI. In addition, intratumoral infiltration of different T-cell subpopulations at the time of first diagnosis was analyzed by immunohistochemistry (n=20) and compared to the occurrence of spontaneous immune responses.
Results: Altogether, anti-tumor immune responses against autologous tumor lysate were detected in 61/106 patients. Survival analysis revealed a trend towards an improved survival for patients with a spontaneous immune response (p=0.09). Most interestingly, when including extent of tumor resection as a co-variable those patients survived significantly better (p=0.01) who got a complete tumor resection and showed a spontaneous T-cell response against their own tumor. In contrast, in subtotally resected patients the immune response did not seem to improve survival. In line with these observations, occurrence of memory T-cell responses against a set of known GBM-associated antigens (TTR, MAGE A3, S100A9) was only associated with a better survival in those GBM patients who received a complete tumor resection (p=0.04). Finally, frequency of intratumoral memory T-cell infiltration (CD45RO) was also associated with the occurrence of spontaneous immune responses and an improved survival.
Conclusions: The present analysis for the first time depicts on several levels a significant influence of the patient's immune system on the course of the disease in GBM patients. In this regard the most crucial prerequisite seems to be the MRI-based complete tumor resection which most likely results in the removal of the immunosuppressive tumor environment.
