bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A60: NK cell activation and cytotoxicity can be enhanced with chemotherapy in a murine model of glioblastoma.
Authors: Pellegatta Serena , Cantini Gabriele , Pessina Sara , Finocchiaro Gaetano 
Published: August 2014

Abstract
Chemotherapy is currently regarded as a potential ally for cancer immunotherapy. Several anticancer agents, including classical chemotherapeutic compounds, are able to enforce tumor specific immune responses either by inducing the immunogenic death of tumor cells or by modulating key cells for immune suppression or activation.
To determine whether Temozolomide (TMZ), the standard chemotherapeutic agent for glioblastoma and malignant gliomas, could induce tumor immunogenicity, we treated murine GL261 cells with 50 and 150 microM TMZ in vitro for 2, 8 and 20 hours. Flow cytometry showed that the NKG2D ligand, involved in NKG2D-mediated NK cell recognition of tumor cells, was highly expressed by TMZ-treated GL261, whereas GL261 treated with vehicle showed only a weak expression (P &lt; 0.01). B7-H3, an inhibitory molecule for NK cells, significantly decreased in TMZ-treated GL261 cells (P &lt; 0.01). TGF-beta1 and TGF-beta2 concentrations in the supernatant from GL261 treated with TMZ significantly decreased, as shown by ELISA (from 23.2 ± 2.5 and 478.4 ± 19.3 in vehicle to 13.2 ± 2.2 and 283.8 ± 25.9 in TMZ-treated cells, respectively, P &lt; 0.0001).
We therefore studied the effects of TMZ on anti-tumor NK cell response by treating mice 7 days after intracranial implantation of GL261 gliomas with intraperitoneal injections of TMZ (5mg/kg) or vehicle (control mice) for 5 days. Five mice were sacrificed 20 hours after treatment on days 1-5: brain, spleen and blood were harvested and analyzed by flow cytometry.
Trafficking of NKp46+ NK1.1+ CD3- NK cells in blood but not in spleen and their homing ability into the brain significantly increased in TMZ-treated compared to control mice after the second administration of TMZ (7.5 ± 1.4 vs 2.3 ± 1.2, P = 0.001; 10.9 ± 0.4 vs. 3.9 ± 0.6, P = 0.005, respectively). Notably TMZ led to an enrichment of CD11bhigh CD27high NK cells, the most potent effector cells.
To verify NK anti-glioma activity, NK1.1 positive cells were isolated from blood and brain of treated and control mice using magnetic separation and incubated with GL261 cells. NK cell cytotoxicity from TMZ-treated mice was significantly higher than that NK cells from control mice.
These results support the contention that chemotherapy may induce enhancement of NK cell response and open new opportunities to design novel combined therapies reversing the immune suppressive role of glioblastoma and unmasking the therapeutic potential of NK responses.
Citation Format: Serena Pellegatta, Gabriele Cantini, Sara Pessina, Gaetano Finocchiaro. NK cell activation and cytotoxicity can be enhanced with chemotherapy in a murine model of glioblastoma. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A60.
Abstract A61: MDSC phenotypes but not Tregs predict patient survival in unresectable stage IV melanoma independently of the type of treatment applied.
Authors: Zelba Henning , Weide Benjamin , Martens Alexander , Pawelec Graham 
Published: August 2014

Abstract
Malignant melanoma is the most aggressive and treatment-resistant form of skin cancer with a steadily increasing incidence. Experimental immunotherapies may result in dramatic tumour regressions but only in a minority of patients. Defining biomarkers allowing identification of those who will survive long-term is crucial to understanding why this is so, and to patient selection. Here, we assessed myeloid-derived suppressor cells (MDSC) and regulatory T cells (Tregs) for their association with survival in late-stage melanoma. We investigated their prognostic value in peripheral blood by polychromatic flow cytometry in a prospective study of 78 patients with unresectable stage IV melanoma treated in a variety of different ways (different peptide vaccinations, ipilimumab, chemotherapy, etc). Thus far, this had only been analyzed in small cohorts and with equivocal results. We investigated four different populations of MDSCs (CD14+CD11b+HLA-DRlo, CD14+CD15+CD11b+, CD14+IL4Ra+ and CD14-CD15+IL4Ra+) that have been associated with poorer outcome in cancers other than melanoma. Tregs were identified as CD4+CD25+FoxP3+ and stratified into CD4+CD45RA+FoxP3lo (resting) and CD4+CD45RA-FoxP3hi (activated) Tregs. We found that the percentages of Tregs in patients were significantly greater than in healthy controls, but differences between patients in their frequencies were not associated with overall survival. In contrast, percentages of the four MDSC populations were not generally different in melanoma patients and controls. However, higher percentages of one population of MSDCs, CD14+CD11b+HLA-DRlo cells, did correlate with shorter survival in Kaplan-Meier analysis and were even superior to the M category in predicting patient survival. These results suggest the importance and potential usefulness of quantifying distinct MDSC populations in the peripheral blood of patients with melanoma for predicting the likelihood of responsiveness to therapy and long-term survival, independently of the nature of their treatment. This is consistent with the notion that anti-tumour immunity plays a crucial role in cancer survivorship, no matter which treatment is applied.
Citation Format: Henning Zelba, Benjamin Weide, Alexander Martens, Graham Pawelec. MDSC phenotypes but not Tregs predict patient survival in unresectable stage IV melanoma independently of the type of treatment applied. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A61.
Abstract A63: Melanoma-educated CD14+ monocytes become myeloid-derived suppressor cell-like and are potent inhibitors of autologous T cells through Cox-2 production and STAT-3 signaling.
Authors: Mao Yumeng , Poschke Isabel , Coaña Yago Pico de , Wennerberg Erik , Lundqvist Andreas , Kiessling Rolf 
Published: August 2014

Abstract
Tumors can suppress the host immune system through a variety of cellular mechanisms, such as regulatory T cells, tumor-associated macrophages and most recently discovered, myeloid-derived suppressor cells (MDSCs). We have previously demonstrated that CD14+HLA-DRlo/- cells accumulate in the peripheral blood of advanced melanoma patients and can suppress autologous T cells ex vivo in a STAT-3-dependent manner. However, the role of MDSCs in the melanoma tumor microenvironment remains to be elucidated. In the current study, early-passage human melanoma cell lines induce significant phenotypic changes on CD14+ monocytes resembling MDSCs in advanced stage melanoma patients. Moreover, such melanoma-educated monocytes strongly impair both autologous T cell proliferation and interferon-γ production. Of note, the induction of the suppressive functions in healthy donor-derived monocytes appears to require tumor contact and/or close proximity to the tumor cells, and is largely dependent on cyclooxygenase-2 (Cox-2) production and activation of STAT-3 signaling pathway. Intriguingly, we have also demonstrated that these two mechanisms are directly involved in the T cell suppression induced by these MDSC-like cells. Last but not least, CD14+ cells isolated ex vivo from advanced stage melanoma patient PBMCs (n=5) exhibited inhibition of autologous T cell functions in a dose dependent manner. Blockade of STAT-3 signaling (p=0.0358, n=4) and superoxide production (p=0.0195, n=4) significantly alleviated the T cell suppression. In conclusion, our data demonstrated the importance of STAT-3 and Cox-2 activity in inducing CD14+ monocytes to exhibit MDSC-like properties, which contributes to our knowledge of how immune suppression is initiated in the human melanoma tumor microenvironment.
Citation Format: Yumeng Mao, Isabel Poschke, Yago Pico de Coaña, Erik Wennerberg, Andreas Lundqvist, Rolf Kiessling. Melanoma-educated CD14+ monocytes become myeloid-derived suppressor cell-like and are potent inhibitors of autologous T cells through Cox-2 production and STAT-3 signaling. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A63.
Abstract A66: IL-33 promotes CD8 T cell effector function and has a potent antitumor activity in vivo.
Authors: Gao Xin , Li Gang , Teng Bo , Yang Qianting , Zhu Yibei , Zhang Xueguang , Finn Olivera J. , Lu Binfeng 
Published: August 2014

Abstract
Interleukin-33 is a member of the IL-1 family of cytokines and is released by stressed cells, necrotic cells or activated innate immune cells such as macrophages during trauma or infection. Thus, IL-33 is thought to serve as an endogenous “danger signal” to trigger inflammation and promote cell mediated immune responses. Prior studies have supported the role of IL-33 in promoting type 2 immune responses but little was known for its role in type 1 immune responses such as the anti-tumor immune response. We have found that that ST2, a receptor for IL-33, is highly expressed in activated CD8 T cells. We have further revealed that, T-bet, a critical transcriptional factor for Th1 differentiation and effector functions, is required for ST2 expression by CD8 T cells, suggesting that ST2 is an integral part of the Th1 gene network in CD8 T cells. Furthermore, we have demonstrated that IL-33 synergized with TCR or IL-12 in increasing both human and mouse CD8 T cell functions such as IFN-γ production. Thus IL-33 can greatly enhance type 1 cell-mediated immune responses in both human and mice. The in vivo relevance of this pathway is examined in a preclinical model of tumor immunity. Our results support a potent function of IL-33 in inhibiting tumor growth and provide a novel therapeutic approach for tumor immunity.
Citation Format: Xin Gao, Gang Li, Bo Teng, Qianting Yang, Yibei Zhu, Xueguang Zhang, Olivera J. Finn, Binfeng Lu. IL-33 promotes CD8 T cell effector function and has a potent antitumor activity in vivo. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A66.
Abstract A82: Neutrophils recruit T-regulatory cells into the tumor via secretion of CCL17 – a new mechanism of tumor immune surveillance.
Authors: Mishalian Inbal , Bayuh rachel , Zolotarov Lida , Levy Liran , Fridlender Zvi Gregorio 
Published: August 2014

Abstract
Introduction: Regulatory T cells (T-regs) play an important role in immunological self-tolerance and are functionally immune-suppressive subsets of T cells. It has been repeatedly shown that T-regs are able to migrate in response to CCL22 and CCL17, and that depletion or inhibition of T-regs can enhance anti-tumor immunity. However, there is still limited data on the mechanisms of accumulation of T-regs within the tumor microenvironment. We have recently described the characteristics of “native” pro-tumorigemic N2 tumor-associated Neutrophils (TAN), and found that TAN significantly up-regulated many chemokines compared to bone-marrow (BM) naïve neutrophils. One of the highly up-regulated genes in TAN is CCL17.
Aims: We aimed to study the role of TAN in the secretion of CCL17 and the recruitment of T-regs into the tumor microenvironment. We hypothesized that the secretion of CCL17 by N2 TAN has an important role in the recruitment of T-regs, thus inhibiting the T-cytotoxic cell activity in the tumor.
Material and Methods: CCL17 production by N1 and N2 TAN and by BM naive Neutrophils was evaluated using ELISA, RT-PCR and IHC staining. We conducted in vivo and in vitro migration assays, and used depletion of TAN to reveal the role of CCL17 secreted from TAN in chemoattraction of T-regs.
Results: N2-TAN were more capable of producing CCL17 ex-vivo than N1-TAN or BM neutrophils. The level of CCL17 secreted from TAN increased during tumor development. In vitro migration assay using CD4+CD25+ cells purified from spleens of naïve mice revealed that migration of T-cells towards TAN were 5.27±1.76 times higher compared to BM neutrophils (p&lt;0.05). Furthermore, migration was inhibited by neutralizing anti-mouse CCL17. In vivo migration assay using the air pouch model strengthen these results, demonstrating that more CD4+CD25+ cells migrated into the pouch when injecting TAN compared to BM neutrophils, again inhibited using anti-CCL17 mAb, suggesting that TAN-induced T-regs chemoattraction is CCL17 dependent. Systemic neutrophil depletion after tumor establishment reduced T-reg migration into the tumor.
Conclusions: Our results show that TAN from established tumors produced CCL17, increasing T-regs migration into the tumor. These results suggest a new indirect mechanism by which TAN may inhibit the anti-tumor immune activity, promoting tumor growth.
Citation Format: Inbal Mishalian, rachel Bayuh, Lida Zolotarov, Liran Levy, Zvi Gregorio Fridlender. Neutrophils recruit T-regulatory cells into the tumor via secretion of CCL17 – a new mechanism of tumor immune surveillance. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A82.
Abstract A88: Identification of factors modulating sensitivity to T cell infiltration in the breast cancer setting via next-generation sequencing.
Authors: Amos Sally , Leeuw Ron de , Kuklev Nikita , Kakal Juzer , Babinsky Sindy , Milne Katy , Kost Sara , Freeman Doug , Holt Rob , Watson Peter , Nelson Brad 
Published: August 2014

Abstract
Clinical and pre-clinical trials have established that killer (CD8+) T cells can recognize and destroy tumors. The challenge of our time is to address barriers to T cell infiltration into solid tumors and thereby make cancer immunotherapy a powerful, broadly applicable treatment modality. Bilateral breast cancer represents a unique opportunity to identify those proteins that modulate immune cell entry into solid tumors. Bilateral synchronous breast cancer is when tumors arise independently in separate breasts of the same patient at the same time. Similar to the powerful use of “twin studies” in epidemiology, bilateral tumors provide an opportunity to explore two independent tumorigenic events against a common genetic (and immunological) background. We hypothesise that the sensitivity of breast cancers to T cell infiltration can be predicted on the basis of their molecular profiles. To assess this question, a cohort of bilateral and unilateral breast cancer tissues has been assembled in collaboration with CTRNet-affiliated biobanks. Our objective was to identify 10 tumor pairs with differential T cell infiltration. Here we present the novel protocol for multi-colour brightfield immunohistochemistry (IHC) which was used to quantitate multiple lymphocyte subsets in these precious specimens at the same time. A workflow for automated image collection is presented, which is geared to the analysis of whole-tumour sections. Our results demonstrate that bilateral breast tumors often show differential lymphocyte infiltration despite being exposed to the same level of systemic immunity. Paired tumors will be subjected to whole transcriptome sequencing and lymphocyte receptor spectratyping to identify proteins that distinguish infiltrated from non-infiltrated tumors. Thus, patients with bilateral breast cancer have provided a powerful, translationally-relevant opportunity to study local barriers to T cell infiltration in solid tumors.
Citation Format: Sally Amos, Ron de Leeuw, Nikita Kuklev, Juzer Kakal, Sindy Babinsky, Katy Milne, Sara Kost, Doug Freeman, Rob Holt, Peter Watson, Brad Nelson. Identification of factors modulating sensitivity to T cell infiltration in the breast cancer setting via next-generation sequencing. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A88.
Abstract B1: Radiotherapy promotes tumor-specific effector CD8+ T cells via DC activation.
Authors: Gupta Anurag K. , Probst Hans Christian , Vuong Van , Landshammer Alexandro , Muth Sabine , Yagita Hideo , Schwendener Reto , Pruschy Martin , Knuth Alexander , Broek Maries van den 
Published: August 2014

Abstract
Radiotherapy is an important treatment for cancer. The main mode of action is thought to be the irreversible damage to tumor cell DNA, but there is evidence that irradiation mobilizes tumor-specific immunity and recent studies showed that the efficacy of high-dose radiotherapy depends on the presence of CD8+ T cells. We show here that the efficacy of radiotherapy given as a single, high dose (10 Gy) crucially depends on dendritic cells and CD8+ T cells, whereas CD4+ T cells or macrophages are dispensable. We show that local high-dose irradiation results in activation of tumor-associated dendritic cells that in turn support tumor-specific effector CD8+ T cells, thus identifying the mechanism that underlies radiotherapy-induced mobilization of tumor-specific immunity. We propose that – in the absence of irradiation – the activation status of dendritic cells rather than the amount of tumor-derived antigen is the bottleneck, which precludes efficient anti-tumor immunity.
Citation Format: Anurag K. Gupta, Hans Christian Probst, Van Vuong, Alexandro Landshammer, Sabine Muth, Hideo Yagita, Reto Schwendener, Martin Pruschy, Alexander Knuth, Maries van den Broek. Radiotherapy promotes tumor-specific effector CD8+ T cells via DC activation. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B1.
Abstract B14: Minimum effective concentration of paclitaxel improves the effectivity of dendritic cells transfected with tumor RNA.
Authors: Camargo Marcela Rodrigues , Rodrigues Cecília Pessoa , Gorgulho Carolina Mendonça , Zambuzi Fabiana Albani , Galvão Victória Elizabeth , Frederico Juliana Cristina Longo , Penitenti Marcimara , Kaneno Ramon 
Published: August 2014

Abstract
The central role of dendritic cells (DCs) in antigen presentation and induction of antitumor immunity supported the development of antitumor vaccines based on these cells. In previous studies, we have observed that treatment with ultra-low doses of paclitaxel (PAC) modulated human DCs to express the phenotype of mature and activated cells, and stimulated their antigen presentation activity. At the same time, tumor cells treated with low concentrations of drugs became more immunogenic and more susceptible to the lytic activity of cytotoxic T lymphocytes in vitro. Therefore, we aimed to verify if the transfection of DCs with drug-treated tumor cells RNA enhances the effectiveness of DC-based vaccines and if the in vitro effects are reproducible in vivo. Murine colon tumor cells (MC-38) were subcutaneously inoculated in C57Bl/6 mice. At the 10th and 17th days after inoculation, they received a DC vaccine transfected with RNA of MC-38 cells pre-treated with minimum effective concentration of PAC. These DCs expressed 12% higher levels of CD40 and were able to delay the tumor growth when compared with non-treated animals. Although the differences were not significant, our results suggest that the treatment of tumor cells with low concentration of PAC can enhance the immunogenicity of tumor cells, which is transfered for DCs by RNA transfection, and delay tumor growth. Financial support: FAPESP 2009/18331-8; FAPESP 2010/06013-9.
Citation Format: Marcela Rodrigues Camargo, Cecília Pessoa Rodrigues, Carolina Mendonça Gorgulho, Fabiana Albani Zambuzi, Victória Elizabeth Galvão, Juliana Cristina Longo Frederico, Marcimara Penitenti, Ramon Kaneno. Minimum effective concentration of paclitaxel improves the effectivity of dendritic cells transfected with tumor RNA. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B14.
Abstract B20: Immunotherapy as treatment for dogs with glioma.
Authors: Goulart Michelle , Pluhar Elizabeth , Andersen Brian , Seiler Charles , Hunt Matthew , O'Sullivan Gerry , Zhang Zoe , Ohlfest John 
Published: August 2014

Abstract
Gliomas, the most invasive tumors of the brain, are a disparate group of oncological diseases for which there is currently no cure. Despite the use of combination therapy (surgery, radiation and chemotherapy) as the standard of care for patients, limited progress has been made in the control of the disease. Similar to that in humans, dogs develop spontaneous brain tumors that often carry a dismal prognosis regardless of therapeutic intervention. There is an obvious need for new therapies to treat dogs with brain tumors. Cancer immunotherapy, with the premise that tumor-reactive lymphocytes are able to infiltrate the brain to eradicate microscopic disease, is emerging as a promising strategy to treat glioma. To date, very little is known regarding canine glioma treatment outcome and there has been no reported randomized clinical trials examining the use of immunotherapy for treatment of glioma in dogs. A clinical trial using immunotherapy with autologous glioma cell lysate vaccines, combined with the TLR9 agonist CpG oligodeoxynucleotide to treat dogs with glioma, is underway in our laboratory. The objective of the treatment is to induce specific anti-tumor immunity in the brain and to prevent tumor recurrence. Our preliminary results have shown that vaccinated dogs exhibited extended survival when compared with historical controls. Based on western blot and flow cytometric analysis, this therapeutic approach induced tumor-reactive antibody responses with elevation of IgG antibody levels after vaccination. Thus, the examination of immune responses in therapeutic trials conducted in dogs with gliomas should greatly help predict outcomes of similar treatments in humans, and additionally provide an opportunity to accelerate the development of more efficient immunotherapeutic cancer vaccines for treatment of intracranial malignances.
Citation Format: Michelle Goulart, Elizabeth Pluhar, Brian Andersen, Charles Seiler, Matthew Hunt, Gerry O'Sullivan, Zoe Zhang, John Ohlfest. Immunotherapy as treatment for dogs with glioma. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B20.