Adjuvant immunotherapy of C6 glioma in rats with pertussis toxin

• Published in: Journal of cancer research and clinical oncology Vol. 138; no. 1; pp. 23 - 33
• Main Authors: Orozco-Morales, Mario, Sánchez-García, Francisco-Javier, Guevara-Salazar, Patricia, Arrieta, Oscar, Hernández-Pedro, Norma Y., Sánchez-García, Aurora, Perez-Madrigal, Rodolfo, Rangel-López, Edgar, Pineda, Benjamín, Sotelo, Julio
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.01.2012; Springer; Springer Nature B.V
• Subjects: Adjuvants; Animals; Antineoplastic agents; Apoptosis; Apoptosis - drug effects; Apoptosis - immunology; Biological and medical sciences; Blood; Brain cancer; Cancer Research; CD25 antigen; CD4 antigen; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; Chemokine CCL3 - biosynthesis; Chemokine CCL3 - genetics; Chemokine CCL3 - immunology; Cytokines; Female; Foxp3 protein; Gene expression; Glioblastoma; Glioma - drug therapy; Glioma - immunology; Glioma - pathology; Glioma cells; Granzymes - biosynthesis; Granzymes - genetics; Granzymes - immunology; Hematology; Immune system; Immunologic Factors - immunology; Immunologic Factors - pharmacology; Immunomodulation; Immunosuppressive agents; Immunotherapy; Inflammation; Interleukin 6; Interleukin-2 Receptor alpha Subunit - immunology; Interleukin-6 - biosynthesis; Interleukin-6 - genetics; Interleukin-6 - immunology; Internal Medicine; Lymphocytes T; macrophage inflammatory protein 1; Macrophages - drug effects; Macrophages - immunology; Medical sciences; Medicine; Medicine & Public Health; Monocyte chemoattractant protein 1; Neurology; Oncology; Original Paper; Perforin; Perforin - biosynthesis; Perforin - genetics; Perforin - immunology; pertussis toxin; Pertussis Toxin - immunology; Pertussis Toxin - pharmacology; Pharmacology. Drug treatments; Prognosis; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Rodents; Spleen; Surgery; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; Tumors of the nervous system. Phacomatoses; C6 glioma; Regulatory T cells; Glioblastoma multiforme; Pertussis toxin; Immunotherapeutic; Nervous system diseases; Rat; Rodentia; Adjuvant treatment; Malignant tumor; Malignant glioma; Vertebrata; Mammalia; Animal; Immunotherapy; Central nervous system disease; T-Lymphocyte; Regulatory cell; Cancer
• DOI: 10.1007/s00432-011-1069-y
• ISSN: 0171-5216; 1432-1335

Purpose In spite of the recent advances in surgery and antitumor drugs, the brain tumors, like glioblastoma, have shown a poor prognosis. The aim of this study was to determine the effect of pertussis toxin (PTx) as immunomodulatory molecule on glial tumors induced by C6 glioma cells. Methods Given the pleiotropic effect of PTx on the immune system, we analyzed the effect of PTx on CD4+/CD25+/FoxP3+ (Treg) cells like as immunotherapeutic adjuvant. Thirty rats with a glial tumor of 1.5 cm in diameter were separated in two groups: the first group was treated with PTx and the second group was non-treated (controls). Tumoral volume was measured weekly; tumor, blood and spleen were taken for analysis of subpopulations of T cells, apoptotic index and cytokine contents, in both groups. Results We observed a significant decrease in tumor volume in the PTx group; this was associated with a decreased in the number of Treg cells, in both spleen and tumor. The percentage of apoptotic cells was increased as compared with that of controls. The production of proinflammatory cytokines was increased in mRNA for IL-6 as well as a small increase in the mRNA expression of perforin and granzime in tumors from rats treated with PTx. No changes were found in the mRNA expression of MCP-1 and MIP-1α. Conclusion These results suggest that PTx could be an immunotherapeutic adjuvant in the integral therapy against glial tumors.