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Increased seroreactivity to glioma-expressed antigen 2 in brain tumor patients under radiation.

Heisel SM, Ketter R, Keller A, Klein V, Pallasch CP, Lenhof HP, Meese E - PLoS ONE (2008)

Bottom Line: We established an ELISA assay to analyze reactivity of 24 glioblastoma patients over a period of several months.As control we used 30 sera from healthy donors as well as 30 sera from lung cancer patients.Antigens that become immunogenic with an increased antibody response as result of radiation can serve as ideal targets for immunotherapy of human tumors.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Genetics, Saarland University Medical School, Homburg/Saar, Germany.

ABSTRACT

Background: Surgery and radiation are the mainstays of therapy for human gliomas that are the most common primary brain tumors. Most recently, cell culture and animal studies provided the first convincing evidence that radiation not only eliminates tumor cells, but also modulates the immune response and likely improves anti-tumor immunotherapy.

Methodology/principal findings: We present an in vivo study that analyzes the effects of radiation on the immune response in tumor patients. As readout system, we utilized the reactivity of glioma patients' sera against antigen GLEA2 as the most frequent antigen immunogenic in glioblastoma patients. We established an ELISA assay to analyze reactivity of 24 glioblastoma patients over a period of several months. As control we used 30 sera from healthy donors as well as 30 sera from lung cancer patients. We compared the course of GLEA2 seroreactivity at different times prior, during and after radiation. The GLEA2 seroreactivity was increased by the time of surgery, decreased after surgery, increased again under radiation, and slightly decreased after radiation.

Conclusions/significance: Our results provide in vivo evidence for an increased antibody response against tumor antigens under radiation. Antigens that become immunogenic with an increased antibody response as result of radiation can serve as ideal targets for immunotherapy of human tumors.

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Related in: MedlinePlus

Individual course of GLEA2 seroreactivity.Each mark represents the GLEA2 value of a single patient. (A) Comparison of GLEA2 seroreactivities prior and after surgery. (B) Comparison of GLEA2 seroreactivities after surgery and prior to radiation. (C) Comparison of GLEA2 seroreactivities prior and during radiation. (D) Comparison of GLEA2 seroreactivities during and after radiation. On the right of each figure, a histogram of the quotient of GLEA2 values at the two time points is shown.
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pone-0002164-g002: Individual course of GLEA2 seroreactivity.Each mark represents the GLEA2 value of a single patient. (A) Comparison of GLEA2 seroreactivities prior and after surgery. (B) Comparison of GLEA2 seroreactivities after surgery and prior to radiation. (C) Comparison of GLEA2 seroreactivities prior and during radiation. (D) Comparison of GLEA2 seroreactivities during and after radiation. On the right of each figure, a histogram of the quotient of GLEA2 values at the two time points is shown.

Mentions: To follow up the GLEA2 seroreactivity of each individual patient, we compared GLEA2 values between two consecutive time points. For one third of the patients the GLEA2 values were similar before and after surgery. In Figure 2A, GLEA2 values on or near the diagonal indicate these cases. For the majority of the remaining cases we found an increase of GLEA2 values after surgery visualized by GLEA2 values above the diagonal in Figure 2A. For the minority of cases we found a decrease in GLEA2 values after surgery visualized by the values below the diagonal. Likewise, we compared the GLEA2 values after surgery and prior to radiation for each patient. As demonstrated in Figure 2B we found more GLEA2 values below the diagonal than above indicating a decrease of GLEA2 values. Comparing the GLEA2 values before and during radiotherapy, we found the majority of the values above the diagonal indicating a strong increase of GLEA2 seroreactivity (Figure 2C). Comparing the GLEA2 values during and after radiation we found similar numbers of GLEA2 values above or below the diagonal indicating that GLEA2 values did not obviously change after radiation (Fig. 2D). To compute significance values for consecutive points in time, we performed an unpaired two tailed Wilcoxon Mann-Whitney tests. Consistent with the analysis of the overall GLEA2 seroreactivity frequency, the differences between GLEA2 values prior to radiation and during radiation were significant (p-value of 0.014).


Increased seroreactivity to glioma-expressed antigen 2 in brain tumor patients under radiation.

Heisel SM, Ketter R, Keller A, Klein V, Pallasch CP, Lenhof HP, Meese E - PLoS ONE (2008)

Individual course of GLEA2 seroreactivity.Each mark represents the GLEA2 value of a single patient. (A) Comparison of GLEA2 seroreactivities prior and after surgery. (B) Comparison of GLEA2 seroreactivities after surgery and prior to radiation. (C) Comparison of GLEA2 seroreactivities prior and during radiation. (D) Comparison of GLEA2 seroreactivities during and after radiation. On the right of each figure, a histogram of the quotient of GLEA2 values at the two time points is shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2366063&req=5

pone-0002164-g002: Individual course of GLEA2 seroreactivity.Each mark represents the GLEA2 value of a single patient. (A) Comparison of GLEA2 seroreactivities prior and after surgery. (B) Comparison of GLEA2 seroreactivities after surgery and prior to radiation. (C) Comparison of GLEA2 seroreactivities prior and during radiation. (D) Comparison of GLEA2 seroreactivities during and after radiation. On the right of each figure, a histogram of the quotient of GLEA2 values at the two time points is shown.
Mentions: To follow up the GLEA2 seroreactivity of each individual patient, we compared GLEA2 values between two consecutive time points. For one third of the patients the GLEA2 values were similar before and after surgery. In Figure 2A, GLEA2 values on or near the diagonal indicate these cases. For the majority of the remaining cases we found an increase of GLEA2 values after surgery visualized by GLEA2 values above the diagonal in Figure 2A. For the minority of cases we found a decrease in GLEA2 values after surgery visualized by the values below the diagonal. Likewise, we compared the GLEA2 values after surgery and prior to radiation for each patient. As demonstrated in Figure 2B we found more GLEA2 values below the diagonal than above indicating a decrease of GLEA2 values. Comparing the GLEA2 values before and during radiotherapy, we found the majority of the values above the diagonal indicating a strong increase of GLEA2 seroreactivity (Figure 2C). Comparing the GLEA2 values during and after radiation we found similar numbers of GLEA2 values above or below the diagonal indicating that GLEA2 values did not obviously change after radiation (Fig. 2D). To compute significance values for consecutive points in time, we performed an unpaired two tailed Wilcoxon Mann-Whitney tests. Consistent with the analysis of the overall GLEA2 seroreactivity frequency, the differences between GLEA2 values prior to radiation and during radiation were significant (p-value of 0.014).

Bottom Line: We established an ELISA assay to analyze reactivity of 24 glioblastoma patients over a period of several months.As control we used 30 sera from healthy donors as well as 30 sera from lung cancer patients.Antigens that become immunogenic with an increased antibody response as result of radiation can serve as ideal targets for immunotherapy of human tumors.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Genetics, Saarland University Medical School, Homburg/Saar, Germany.

ABSTRACT

Background: Surgery and radiation are the mainstays of therapy for human gliomas that are the most common primary brain tumors. Most recently, cell culture and animal studies provided the first convincing evidence that radiation not only eliminates tumor cells, but also modulates the immune response and likely improves anti-tumor immunotherapy.

Methodology/principal findings: We present an in vivo study that analyzes the effects of radiation on the immune response in tumor patients. As readout system, we utilized the reactivity of glioma patients' sera against antigen GLEA2 as the most frequent antigen immunogenic in glioblastoma patients. We established an ELISA assay to analyze reactivity of 24 glioblastoma patients over a period of several months. As control we used 30 sera from healthy donors as well as 30 sera from lung cancer patients. We compared the course of GLEA2 seroreactivity at different times prior, during and after radiation. The GLEA2 seroreactivity was increased by the time of surgery, decreased after surgery, increased again under radiation, and slightly decreased after radiation.

Conclusions/significance: Our results provide in vivo evidence for an increased antibody response against tumor antigens under radiation. Antigens that become immunogenic with an increased antibody response as result of radiation can serve as ideal targets for immunotherapy of human tumors.

Show MeSH
Related in: MedlinePlus