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Immunotherapy of pediatric brain tumor patients should include an immunoprevention strategy: a medical hypothesis paper.

Driggers L, Zhang JG, Newcomb EW, Ge L, Hoa N, Jadus MR - J. Neurooncol. (2009)

Bottom Line: Adults diagnosed with Glioblastoma multiforme (GBM) are frequently faced with a 7% chance of surviving 2 years compared with pediatric patients with GBM who have a 26% survival rate.An immune response mounted by these pediatric patients might account for their extended life spans, even though the pediatric brain tumors express far fewer total tumor-associated antigens.Here we present a hypothesis that pediatric brain tumor patients might be the best patients to show that immunotherapy can be used to successfully treat established cancers.

View Article: PubMed Central - PubMed

Affiliation: Pathology and Laboratory Medicine Service, Molecular Medicine Health Care Group, VA Long Beach Healthcare System, Box 113, 5901 E. 7th Street, Long Beach, CA, 90822, USA.

ABSTRACT
Adults diagnosed with Glioblastoma multiforme (GBM) are frequently faced with a 7% chance of surviving 2 years compared with pediatric patients with GBM who have a 26% survival rate. Our recent screen of possible glioma-associated antigen precursor protein (TAPP) profiles displayed from different types of pediatric brain tumors showed that pediatric patients contained a subset of the tumor antigens displayed by adult GBM patients. Adult GBM possess at least 27 tumor antigens that can potentially stimulate T cell immune responses, suggesting that these tumors are quite antigenic. In contrast, pediatric brain tumors only expressed nine tumor antigens with mRNA levels that were equivalent to those displayed by adult GBM. These tumor-associated antigens could be used as possible targets of therapeutic immunization for pediatric brain cancer patients. Children have developing immune systems that peak at puberty. An immune response mounted by these pediatric patients might account for their extended life spans, even though the pediatric brain tumors express far fewer total tumor-associated antigens. Here we present a hypothesis that pediatric brain tumor patients might be the best patients to show that immunotherapy can be used to successfully treat established cancers. We speculate that immunotherapy should include a panel of tumor antigens that might prevent the out-growth of more malignant tumor cells and thereby prevent the brain tumor relapse. Thus, pediatric brain tumor patients might provide an opportunity to prove the concept of immunoprevention.

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Related in: MedlinePlus

Differences between adult-derived and pediatric-derived for 3 TAPP genes. The amount of mRNA was quantitated by a ΔCt value on left y-axis in comparison to the 18S RNA. The ΔCt value of 20 was given an arbitrary value of 1 and the fold-difference is presented on right y-axis. The expression of MRP-3, hTert and survivin are shown within their respective boxes. Pediatric GBM patient 847 had the highest expressing mRNA in the MRP-3 cohort, Pediatric GBM patient 1292 displayed the most survivin mRNA and the second most hTert mRNA. Pediatric GBM patient 1476 was the recurrent GBM and had the most hTert mRNA. The legend box indicates the number of tumors that were analyzed. By a student’s t test, all values between the pediatric and adult GBM were statistically significant (P < 0.05)
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Fig2: Differences between adult-derived and pediatric-derived for 3 TAPP genes. The amount of mRNA was quantitated by a ΔCt value on left y-axis in comparison to the 18S RNA. The ΔCt value of 20 was given an arbitrary value of 1 and the fold-difference is presented on right y-axis. The expression of MRP-3, hTert and survivin are shown within their respective boxes. Pediatric GBM patient 847 had the highest expressing mRNA in the MRP-3 cohort, Pediatric GBM patient 1292 displayed the most survivin mRNA and the second most hTert mRNA. Pediatric GBM patient 1476 was the recurrent GBM and had the most hTert mRNA. The legend box indicates the number of tumors that were analyzed. By a student’s t test, all values between the pediatric and adult GBM were statistically significant (P < 0.05)

Mentions: As described above, one TAPP expression profile of 9 antigens was either expressed more in adult GBM compared with pediatric GBM (group 2) or exclusively expressed in adult GBM compared with pediatric GBM (group 3). We will focus on 3 of these tumor antigens: Multi-drug resistance protein-3 (MRP-3), human Telomerase reverse transcriptase (hTert), and Survivin (Fig. 2). These 3 tumor antigens may provide some insight into why pediatric GBM may be easier to treat and why the pediatric GBM patients survive longer than adult GBM patients. Expression of these 3 genes correlates with a poorer prognosis in many different cancer types [5–8], suggesting these genes participate in tumor progression. Studies have shown that CTLs are capable of killing cancer cells expressing these 3 epitopes [9–12]. Hence these adult GBM should still be susceptible to this T cell-mediated cytotoxicity.Fig. 2


Immunotherapy of pediatric brain tumor patients should include an immunoprevention strategy: a medical hypothesis paper.

Driggers L, Zhang JG, Newcomb EW, Ge L, Hoa N, Jadus MR - J. Neurooncol. (2009)

Differences between adult-derived and pediatric-derived for 3 TAPP genes. The amount of mRNA was quantitated by a ΔCt value on left y-axis in comparison to the 18S RNA. The ΔCt value of 20 was given an arbitrary value of 1 and the fold-difference is presented on right y-axis. The expression of MRP-3, hTert and survivin are shown within their respective boxes. Pediatric GBM patient 847 had the highest expressing mRNA in the MRP-3 cohort, Pediatric GBM patient 1292 displayed the most survivin mRNA and the second most hTert mRNA. Pediatric GBM patient 1476 was the recurrent GBM and had the most hTert mRNA. The legend box indicates the number of tumors that were analyzed. By a student’s t test, all values between the pediatric and adult GBM were statistically significant (P < 0.05)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2837156&req=5

Fig2: Differences between adult-derived and pediatric-derived for 3 TAPP genes. The amount of mRNA was quantitated by a ΔCt value on left y-axis in comparison to the 18S RNA. The ΔCt value of 20 was given an arbitrary value of 1 and the fold-difference is presented on right y-axis. The expression of MRP-3, hTert and survivin are shown within their respective boxes. Pediatric GBM patient 847 had the highest expressing mRNA in the MRP-3 cohort, Pediatric GBM patient 1292 displayed the most survivin mRNA and the second most hTert mRNA. Pediatric GBM patient 1476 was the recurrent GBM and had the most hTert mRNA. The legend box indicates the number of tumors that were analyzed. By a student’s t test, all values between the pediatric and adult GBM were statistically significant (P < 0.05)
Mentions: As described above, one TAPP expression profile of 9 antigens was either expressed more in adult GBM compared with pediatric GBM (group 2) or exclusively expressed in adult GBM compared with pediatric GBM (group 3). We will focus on 3 of these tumor antigens: Multi-drug resistance protein-3 (MRP-3), human Telomerase reverse transcriptase (hTert), and Survivin (Fig. 2). These 3 tumor antigens may provide some insight into why pediatric GBM may be easier to treat and why the pediatric GBM patients survive longer than adult GBM patients. Expression of these 3 genes correlates with a poorer prognosis in many different cancer types [5–8], suggesting these genes participate in tumor progression. Studies have shown that CTLs are capable of killing cancer cells expressing these 3 epitopes [9–12]. Hence these adult GBM should still be susceptible to this T cell-mediated cytotoxicity.Fig. 2

Bottom Line: Adults diagnosed with Glioblastoma multiforme (GBM) are frequently faced with a 7% chance of surviving 2 years compared with pediatric patients with GBM who have a 26% survival rate.An immune response mounted by these pediatric patients might account for their extended life spans, even though the pediatric brain tumors express far fewer total tumor-associated antigens.Here we present a hypothesis that pediatric brain tumor patients might be the best patients to show that immunotherapy can be used to successfully treat established cancers.

View Article: PubMed Central - PubMed

Affiliation: Pathology and Laboratory Medicine Service, Molecular Medicine Health Care Group, VA Long Beach Healthcare System, Box 113, 5901 E. 7th Street, Long Beach, CA, 90822, USA.

ABSTRACT
Adults diagnosed with Glioblastoma multiforme (GBM) are frequently faced with a 7% chance of surviving 2 years compared with pediatric patients with GBM who have a 26% survival rate. Our recent screen of possible glioma-associated antigen precursor protein (TAPP) profiles displayed from different types of pediatric brain tumors showed that pediatric patients contained a subset of the tumor antigens displayed by adult GBM patients. Adult GBM possess at least 27 tumor antigens that can potentially stimulate T cell immune responses, suggesting that these tumors are quite antigenic. In contrast, pediatric brain tumors only expressed nine tumor antigens with mRNA levels that were equivalent to those displayed by adult GBM. These tumor-associated antigens could be used as possible targets of therapeutic immunization for pediatric brain cancer patients. Children have developing immune systems that peak at puberty. An immune response mounted by these pediatric patients might account for their extended life spans, even though the pediatric brain tumors express far fewer total tumor-associated antigens. Here we present a hypothesis that pediatric brain tumor patients might be the best patients to show that immunotherapy can be used to successfully treat established cancers. We speculate that immunotherapy should include a panel of tumor antigens that might prevent the out-growth of more malignant tumor cells and thereby prevent the brain tumor relapse. Thus, pediatric brain tumor patients might provide an opportunity to prove the concept of immunoprevention.

Show MeSH
Related in: MedlinePlus