Journal Title
Title of Journal: Cancer Immunol Immunother
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Abbravation: Cancer Immunology, Immunotherapy
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Publisher
Springer Berlin Heidelberg
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Authors: Sara Fritzell Emma Sandén Sofia Eberstål Edward Visse Anna Darabi Peter Siesjö
Publish Date: 2013/06/18
Volume: 62, Issue: 9, Pages: 1463-1474
Abstract
Despite temozolomide TMZ treatment the prognosis for patients with glioblastoma multiforme is still dismal As dose escalation of TMZ is limited by systemic toxicity intratumoral delivery emerges as an attractive treatment modality which may sustain cytotoxic drug concentrations intratumorally and induce immunogenic cell death Both clinical and experimental gliomas have responded to immunotherapy but the benefit of simultaneous chemo and immunotherapy is inadequately studied Here we monitored survival of GL261bearing C57BL/6 mice following a 3day treatment with either intratumoral TMZ microosmotic pump 42 mg/kg/day or systemic TMZ ip injections 50 mg/kg/day alone or combined with immunization using GMCSF secreting GL261 cells Peripheral and intratumoral leukocytes were analyzed by flow cytometry and immunohistochemistry Intratumoral TMZ induced higher survival rate than systemic TMZ 45 vs 8 When T cells were depleted following intratumoral TMZ the therapeutic effect was completely abrogated 0 survival Intratumoral TMZ synergistically increased survival rate of immunized mice from 25 to 83 while systemic TMZ failed 0 While systemic TMZ induced a transient leukopenia intratumoral TMZ and immunotherapy sustained the proliferation of CD8+ T cells and decreased the number of intratumoral immunosuppressive cells In conclusion intratumoral TMZ alone or in combination with immunotherapy could cure gliomabearing mice due to attenuation of local immunosuppression and increase in potential effector immune cellsThis work was supported by the Hans and Märit Rausing Charitable Trust to LG Salford the Swedish Childhood Cancer Foundation the NeuroblastomaCNS Network NBCNS Foundation the Skåne region funds ALF all to P Siesjö and the Royal Physiographic Society in Lund to A Darabi We would like to thank Hanna Fritzell and Jeremy Wales for reviewing the manuscript
Keywords:
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Other Papers In This Journal:
- Successful induction of clinically competent dendritic cells from granulocyte colony-stimulating factor-mobilized monocytes for cancer vaccine therapy
- Second International Symposium on Cancer Biology (ISCB), November 14–16, 2011, at the National Institute of Immunology, New Delhi, India
- Cancer/testis antigens expression and autologous serological response in a set of Brazilian non-Hodgkin’s lymphoma patients
- Saccharomyces cerevisiae , the Baker’s Yeast, suppresses the growth of Ehrlich carcinoma-bearing mice
- Higher numbers of T-bet + intratumoral lymphoid cells correlate with better survival in gastric cancer
- Maturation of monocyte-derived dendritic cells with Toll-like receptor 3 and 7/8 ligands combined with prostaglandin E 2 results in high interleukin-12 production and cell migration
- Increase in CD14 + HLA-DR −/low myeloid-derived suppressor cells in hepatocellular carcinoma patients and its impact on prognosis
- CD8+ T cells specific for the androgen receptor are common in patients with prostate cancer and are able to lyse prostate tumor cells
- Soluble factors released by activated cytotoxic T lymphocytes interfere with death receptor pathways in neuroblastoma
- Epigenetic regulation of immune escape genes in cancer
- The small molecule TGF-β signaling inhibitor SM16 synergizes with agonistic OX40 antibody to suppress established mammary tumors and reduce spontaneous metastasis
- Dendritic cells efficiently acquire and present antigen derived from lung cancer cells and induce antigen-specific T-cell responses
- Expression of complement protein C5a in a murine mammary cancer model: tumor regression by interference with the cell cycle
- −509C>T polymorphism in the TGF-β1 gene promoter, impact on the hepatocellular carcinoma risk in Chinese patients with chronic hepatitis B virus infection
- Bridging the innate and adaptive immune responses against cancer: 95th AACR meeting 2004
- Heterogeneity of CD8 + tumor-infiltrating lymphocytes in non-small-cell lung cancer: impact on patient prognostic assessments and comparison of quantification by different sampling strategies
- Impact of KIR/HLA ligand combinations on immune responses in malignant melanoma
- Cardiac allograft rejection as a complication of PD-1 checkpoint blockade for cancer immunotherapy: a case report
- Early developmental expression of a normally tumor-associated and drug-inhibited cell surface-located NADH oxidase (ENOX2) in non-cancer cells
- Human mucin MUC1 RNA undergoes different types of alternative splicing resulting in multiple isoforms
- H 2 O 2 production within tumor microenvironment inversely correlated with infiltration of CD56 dim NK cells in gastric and esophageal cancer: possible mechanisms of NK cell dysfunction
- Lenalidomide enhances anti-myeloma cellular immunity
- Epidemiology: allergy history, IgE, and cancer
- Optimal selection of natural killer cells to kill myeloma: the role of HLA-E and NKG2A
- Toward harmonized phenotyping of human myeloid-derived suppressor cells by flow cytometry: results from an interim study
- Oropharyngeal squamous cell carcinomas differentially express granzyme inhibitors
- Chordoma and chondrosarcoma gene profile: implications for immunotherapy
- Serum IgG against Candida predict survival in patients with metastatic renal cell carcinoma
- Extracellular adenosine metabolism in immune cells in melanoma
- Collective action of hematopoietic cell subsets mediates anti-IL10R1 and CpG tumor immunity
- Phase I–II study of lenalidomide and alemtuzumab in refractory chronic lymphocytic leukemia (CLL): effects on T cells and immune checkpoints
- Comparative analysis of monocytic and granulocytic myeloid-derived suppressor cell subsets in patients with gastrointestinal malignancies
- Comparison of AAV/IL-7 autocrine (T cell) versus paracrine (DC) gene delivery for enhancing CTL stimulation and function
- Non-genomic events determining the sensitivity of hemopoietic malignancies to glucocorticoid-induced apoptosis
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