gms | German Medical Science

Objective: Glioblastoma multiforme is the most frequent as well as most malignant brain tumor. With a mean survival of 12–14 months and a long-term survival rate of only three to five percent, prognosis is poor. Nevertheless there are some rare cases with survival even beyond 20 years. Comparatively few clinical studies suggest that the immune system plays a critical role in long-term survival of glioblastoma multiforme. We investigated the association between the expression of immunological markers and long-term survival.

Method: We assessed 14 patients, with primary glioblastoma (time of diagnosis from 1997 until 2008) who survived more than 30 months. They defined the group of long-term survivors (LTS). The longest overall survival was 107 months. As a control 14 short-term survivors (STS) with a maximum survival of 16 months were matched for age, time of diagnosis, Karnofsky index and sex. Paraffin-embedded tumor tissues of these 28 patients were examined immunohistochemically. 9 antigens, related to lymphocyte reaction, namely: CD 4, CD 8, CD 14, CD 20, CD 25, CD 26, CD 57, CD 95 and CD 95-L were determined. All slides were scanned for positive cells under the microscope in ten high-power fields. Positive cells were counted in 40-fold enlargement. Statistical analysis was performed with U-test (Wilcoxon) by SPSS Statistics 19. Furthermore, we screened all patients for IDH R132H mutation and expression of HLA DR II. MGMT-status was considered.

Results: Our group of LTS showed a mean survival of 44 months whereas the control patients survived on average for less than half a year. We proved that all 28 patients showed no IDH R123H-mutation, hence all tested tumors were primary glioblastoma multiforme. HLA DR II antigen expression was not significantly increased in neither LTS nor STS. In tumor tissue of LTS we found a significantly higher quantity of CD 8 (p=0, 0015) and CD 25 (p=0, 0007) positive cells compared to the STS tumor tissue. The higher expression of CD 20 (p=0,0303) and CD 95 (p=0,0279) in LTS was statistically significant, too. CD 26 and CD 57 were strongly positive in LTS as well as in STS. 54% of LTS and 55% of STS showed a methylated MGMT-promotor.

Conclusions: We suggest a beneficial effect of CD 8⁺ and CD 25⁺ lymphocytes on the prognosis of primary glioblastoma, even in regards to long term survival. The effect of CD 20 and CD 95 has to be discussed. Subsequent prospective studies may assess an immunological screening in glioblastoma patients for prognostic value. Our findings should encourage further research on immunotherapy of glioblastoma multiforme.