bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A05: Biphasic anti-tumoral effect of a vascular-disrupting agent triggering STING and tumor regression
Authors: Weiss Julia M. , Guerin Marion , Regnier Fabienne , Thoreau Maxime , Peranzoni Elisa , Feuillet Vincent , Renault Gilles , Guilbert Thomas , Trautmann Alain , Bercovici Nadege 
Published: March 2017

Abstract
Despite significant advances, cancer immunotherapies fail to systematically elicit tumor regression. It is therefore crucial to understand what conditions the efficacy of immune responses against solid tumors. In particular, while the involvement of T lymphocytes does not need to be further proven, their relative contribution and their cooperation with other cells in regressing tumors is still ill defined. We have investigated in a breast tumor model (PyMT-MMTV) the dynamics of the immune response which takes place during the tumor regression induced by a single i.p. injection of DMXAA, a ligand and activator of STING (a key detector of cytoplasmic DNA and of viral infection). We have shown that the DMXAA-induced tumor vascular disruption, visualized by contrast-enhanced ultrasound, and the associated IFNα/β release, conditioned a swift and massive recruitment of neutrophils, followed by a delayed rise in CD8 T cells and inflammatory monocytes in the tumor mass. All these immune cell subsets contributed to the efficacy of tumor regression, as evidenced by in vivo depletion experiments, which, together with dynamic imaging allowed to characterize cooperations between these immune cell subsets. We have analyzed the kinetics of the biphasic effect of DMXAA : vascular disruption followed by an anti-tumoral immune response. These data support the idea that the inflammation in the tumor microenvironment can be modulated to reset immune cell cooperation like in an acute phase of an immune response against foreign pathogens.
Note: This abstract was not presented at the conference.
Citation Format: Julia M. Weiss, Marion Guerin, Fabienne Regnier, Maxime Thoreau, Elisa Peranzoni, Vincent Feuillet, Gilles Renault, Thomas Guilbert, Alain Trautmann, Nadege Bercovici. Biphasic anti-tumoral effect of a vascular-disrupting agent triggering STING and tumor regression. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr A05.
Abstract A08: Dectin-1 signaling drives pancreatic oncogenesis by promoting adaptive immune suppression
Authors: Daley Donnele , Akkad Neha , Mohan Navyatha , Ochi Atsuo , Werba Gregor , Mani Vishnu , Barilla Rocky , Zambirinis Constantinos , Hundeyin Mautin , Lee Ki Buom , Chang Steven , Wang Ding , Gardener Lawrence , Ueberheide Beatrix , Miller George 
Published: March 2017

Abstract
Progression of pancreatic oncogenesis requires immune-suppressive inflammation in cooperation with oncogenic mutations. However, the drivers of intra-tumoral immune tolerance are uncertain. Dectin-1 is an innate immune receptor critical in anti-fungal immunity, but its role in sterile inflammation and oncogenesis is not well-defined. Further, non-pathogen-derived ligands for Dectin-1 have not been characterized. We found that Dectin-1 is highly expressed on myeloid cells in pancreatic ductal adenocarcinoma (PDA). Moreover, Dectin-1 ligation accelerates PDA, whereas Dectin-1 deletion, or blockade of its downstream signaling, was highly protective. We show that Dectin-1 ligates the lectin Galectin-9 in the PDA tumor microenvironment (TME) leading to macrophage-induced adaptive immune suppression. Upon interruption of the Dectin-1–Galectin-9 axis, CD4+ and CD8+ T cells – which are dispensable to PDA progression in hosts with an intact signaling axis – become reprogrammed into indispensable mediators of anti-tumor immunity. These data suggest that Dectin-1 and Galectin-9 are novel and attractive targets for PDA immunotherapy.
Citation Format: Donnele Daley, Neha Akkad, Navyatha Mohan, Atsuo Ochi, Gregor Werba, Vishnu Mani, Rocky Barilla, Constantinos Zambirinis, Mautin Hundeyin, Ki Buom Lee, Steven Chang, Ding Wang, Lawrence Gardener, Beatrix Ueberheide, George Miller. Dectin-1 signaling drives pancreatic oncogenesis by promoting adaptive immune suppression. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr A08.
Abstract A24: Evaluation of the expression of immune functional markers in the tumor microenvironment
Authors: Kim Jeffrey , Li Na , He Mingxiao , Zhang Bingqing , Su Nan , Ma Xiao-Jun , Park Emily 
Published: March 2017

Abstract
Recent clinical successes with immune checkpoint blockades have provided promising immune-based therapeutic approaches for controlling malignancy. While therapeutic antibodies against CTLA-4 and PD-1/PD-L1 have resulted in potent and durable clinical responses in many patients, there still remains an urgent need to develop biomarker based assays to identify patients who may benefit from these approaches while avoiding toxicity and without compromising efficacy. While gene and protein expression of immune cell and checkpoint markers can be obtained through traditional techniques, insight regarding spatial and cell-specific expression within the tumor microenvironment is lacking, particularly in regards to secreted proteins with key immune functions. RNAscope® is an advanced in situ hybridization assay that allows for the visualization of single-cell gene expression, targeting mRNA sequences directly in tissues. The probes designed for this approach permit the detection of secreted markers, including cytokines and chemokines. In our investigation of 60 archived formalin-fixed paraffin embedded non-small cell lung cancer biopsies, expression profiles of immune checkpoint markers and immune functional molecules were evaluated in the tissue environment by RNAscope®. Each of the tumors displayed distinct co-expression patterns of immune checkpoint markers as well as varying levels of cytokines (TGFβ, IFNγ, and TNFα) and chemokines, which were measured in respect to their relative location in the tumor or stromal regions. Additionally, the detection of immune cell markers were used to pinpoint the location of infiltrating lymphocytes. The methods and findings in this study provide a valuable glimpse into the understanding of key immune functional markers in the tumor microenvironment to potentially advance treatment opportunities in this era of immuno-oncology therapies.
Citation Format: Jeffrey Kim, Na Li, Mingxiao He, Bingqing Zhang, Nan Su, Xiao-Jun Ma, Emily Park. Evaluation of the expression of immune functional markers in the tumor microenvironment. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr A24.
Abstract A39: Cholangiocarcinoma-exposed cytokine-induced killer cells developed senescence and exhaustion
Authors: Wongkajornsilp Adisak , Sawatpiboon Nathawadee , Duangsa-ard Sunisa , Kasetsinsombat Kanda , Maneechotesuwan Kittipong , Hongeng Suradej 
Published: March 2017

Abstract
The existence of cellular exhaustion and senescence have been well-documented in T cells, but not yet in CIK cells. The exposure of CIK cells to HubCCA1 cholangiocarcinoma cells resulted in sustaining the proportion of CD3+CD56+ subset at the expense of that of the pure T cell (CD3+CD56-) subset. All major subsets (CD3+CD56+, T cell subsets, and NK cell (CD3-CD56+ subset) of the survived CIK cells were inflicted with increasing senescence markers (KLRG1, CTLA4, and CD57) upon the exposure length. However, CD28, a T cell activation marker, was up-regulated in CD3+CD56+ and NK cell subsets upon tumor exposure, but was suppressed in T cell subset. The co-culture of CIK cells with dendritic cells (DCs) could alleviate CD57, but not KLRG1 nor CTLA4. For exhaustion, the co-culture with DCs could lower the level of PD-1 in CD3+CD56+ and T cell subset, but was unable to withstand the massive up-regulation of PD-1 and Tim-3 in all 3 major subsets upon the tumor exposure. The co-culture with DCs raised the proportion of Treg (CD4+CD25+Foxp3+) subset in CIK cells, but surprisingly reversed by the eventual exposure to tumor cells. In summary, the exposure of CIK cells to tumor cells rendered the development of senescence and exhaustion to the CIK cells. The co-culture of CIK cells with DCs had limited role in preventing these opposing effects.
Citation Format: Adisak Wongkajornsilp, Nathawadee Sawatpiboon, Sunisa Duangsa-ard, Kanda Kasetsinsombat, Kittipong Maneechotesuwan, Suradej Hongeng. Cholangiocarcinoma-exposed cytokine-induced killer cells developed senescence and exhaustion. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr A39.
Abstract A40: Class IIa HDAC inhibition promotes an anti-tumor macrophage phenotype that induces breast tumor regression and inhibits metastasis
Authors: Guerriero Jennifer L. , Sotayo Alaba , Ponichtera Holly , Pourzia Alexandra , Schad Sara , Carrasco Ruben , Suzan Lazo , Bronson Roderick , Letai Anthony 
Published: March 2017

Abstract
While tumor-associated macrophages (TAMs) often have net pro-tumor effects, their embedded location and their untapped potential provide impetus to the discovery of strategies to turn them against tumors. We recently reported that a first in class selective class IIa HDAC inhibitor (TMP195) influenced human monocyte responses to colony stimulating factors CSF-1 and CSF-2 in vitro. Here, we utilize a macrophage-dependent autochthonous mouse model of breast cancer to demonstrate that in vivo TMP195 treatment alters the tumor microenvironment and reduces tumor burden and pulmonary metastases through macrophage modulation. TMP195 induces recruitment and differentiation of highly phagocytic and stimulatory macrophages within tumors. Furthermore, combining TMP195 with chemotherapy regimens or T-cell checkpoint blockade in this model significantly enhances the durability of tumor reduction. These data introduce class IIa HDAC inhibition as a novel means to harness the anti-tumor potential of macrophages to enhance cancer therapy.
Citation Format: Jennifer L. Guerriero, Alaba Sotayo, Holly Ponichtera, Alexandra Pourzia, Sara Schad, Ruben Carrasco, Lazo Suzan, Roderick Bronson, Anthony Letai. Class IIa HDAC inhibition promotes an anti-tumor macrophage phenotype that induces breast tumor regression and inhibits metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr A40.
Abstract B31: IRAK-4 signaling in melanoma contributes to reduced expression of inflammatory factors in vitro while contributing to tumor growth in vivo
Authors: Lasola Jackline Joy Martin , Geng Degui , Shrestha Rojesh , Davila Eduardo 
Published: March 2017

Abstract
An underlying and universal hindrance to T-cell-based cancer therapies is the development of immunosuppressive mechanisms that in large part originate from the persistent expression of inflammatory factors. Understanding the fundamental mechanisms that regulate chronic inflammation and targeting of this pathway(s) is critical for developing effective strategies to restore anti-tumor T-cell activity. We recently reported that the IL-1 receptor associated kinase-4 (IRAK-4) is over-expressed and activated in most melanoma cases. IRAK-4 is a central kinase in the inflammatory process that regulates the expression of various inflammatory and immunosuppressive molecules. Inhibiting IRAK-4 activity in melanoma drastically reduced the expression of various inflammatory factors in vitro. Furthermore, IRAK-4 signaling in melanoma contributed to tumor growth in vivo and was associated with an increased frequency of phenotypically exhausted (PD1+Lag3+) tumor infiltrating T-cells, myeloid derived suppressor cells, and a trend toward higher numbers of CD4+ T regs. Ongoing studies are focused on testing the hypothesis that targeting IRAK-4 signaling in tumor cells will alter the expression of inflammatory factors in the tumor environment which will reduce immunosuppression and sensitize melanoma to T-cell-mediated killing.
Citation Format: Jackline Joy Martin Lasola, Degui Geng, Rojesh Shrestha, Eduardo Davila. IRAK-4 signaling in melanoma contributes to reduced expression of inflammatory factors in vitro while contributing to tumor growth in vivo. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr B31.
Abstract B38: Non-cytotoxic effects of the chemotherapeutic agent gemcitabine can alter the immunophenotype of tumor cells in in vitro culture
Authors: Gravett Andrew M. , Copier John P. , Liu Wai M. , Cranage Martin P. , Dalgleish Angus G. 
Published: March 2017

Abstract
In addition to their cytotoxic/cytostatic properties, some chemotherapeutics have shown a remarkable capacity to modulate immune response. One such chemotherapy is the antimetabolite, gemcitabine (GEM). GEM has been shown to influence the quantity and activation of certain immune cell subsets when used in vivo. It has also been demonstrated that administration of GEM in conjunction with immunotherapy, such as dendritic cell vaccination, is beneficial in terms of overall survival and progression-free survival. The purpose of this study is to investigate if GEM can influence the way that tumor cells surviving treatment are regarded by the immune system. Our group has found that short-term in vitro culture with GEM enhances expression of human leukocyte antigen (HLA) class I, CD95, NKG2D ligands and TRAIL receptors on tumor cell lines. These molecules are all cell surface proteins important for the efficient surveillance and effector function of the immune system. The HLA class I increase is beta-2-microglobulin dependent and changes are underpinned by ERK, JNK and RelB-NFkB signalling pathways. Furthermore, culture with GEM induces immunoproteasomal components LMP2 and MECL-1 in tumor cells and, subsequently, the peptide antigen repertoire displayed on HLA class I is altered. The changes in peptide characteristics include amino acid anchor residue modifications which render the peptides likely to favor binding alternative HLA-allotypes. The renovation of the peptidome displayed by HLA class I may reveal sub-dominant immunogens to T-cells. Taken together, these changes may render tumor cells more sensitive to immune cell-mediated lysis. These data help explain observations made in previous in vivo studies, advise as to which novel antigens could be utilised in future vaccination protocols and lend further credence to the idea that chemotherapy and immunotherapy could be used in combination.
Citation Format: Andrew M. Gravett, John P. Copier, Wai M. Liu, Martin P. Cranage, Angus G. Dalgleish. Non-cytotoxic effects of the chemotherapeutic agent gemcitabine can alter the immunophenotype of tumor cells in in vitro culture. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr B38.
Abstract B55: The alarmin IL-33 is expressed in breast cancer: An emerging role in breast cancer immunity via the activation of NK cells?
Authors: Blanc Elena , Eberhardt Anais , Herbulot Jennifer , Beux Céline Le , Colombe Amelie , Morel Anne-Pierre , Saintigny Pierre , Charrier Emilie , Marcais Antoine , Treilleux Isabelle , Walzer Thierry , Caux Christophe , Bendriss-Vermare Nathalie 
Published: March 2017

Abstract
Interleukin (IL)-33 is an alarmin belonging to the IL-1 family. Through its receptor ST2, IL-33 promotes both type 1 and type 2 immune responses depending on i) the type of responding cells and ii) the microenvironment in damaged tissues. Paradoxical roles of IL-33 have been reported in the context of cancer. Indeed, experimental models of murine mammary carcinoma and clinical observations from breast cancer (BC) patients suggest a protumoral role for IL-33, while antitumor effects of IL-33 via T cell and NK cell activation have also been described in mice. These observations prompted us to revisit the role of IL-33/ST2 axis in BC immunity by investigating the expression of IL-33 in tumors and its impact on Natural Killer (NK) cells biology, which exert anti-tumoral properties via cytokine production and cytotoxic function. Using immunohistochemistry (IHC) as well as mRNA expression analyses (RTqPCR or in silico analyses using public transcriptomic datasets from human breast tumors), we observed that IL-33 is expressed at higher levels in i) Ductal carcinoma in situ (DCIS) compared to invasive breast cancer (IBC), especially in the stroma and ii) triple-negative BC. In situ, IL-33 was found to be expressed in endothelial cells and scattered cells within the stroma of breast tumors. Furthermore, we showed that IL-33, in combination with IL-12, i) potentiates greatly the production of IFN-γ (x1000) by NK cells, in an ST2-dependent manner, ii) induces CD25 and CD69 on their surface, iii) stimulates intracellular NFκB/p38MAPK/mTOR signaling pathways, and iii) increases their natural cytotoxicity towards K562 target cells as well as their proliferation. Importantly, we have some evidence that IL-33 activates a subset of CD56intermediate NK cells. Altogether, our observations are in favor of an NK-mediated antitumor role of IL-33 in cancer that we are currently investigating in a mouse tumor model in vivo.
Citation Format: Elena Blanc, Anais Eberhardt, Jennifer Herbulot, Céline Le Beux, Amelie Colombe, Anne-Pierre Morel, Pierre Saintigny, Emilie Charrier, Antoine Marcais, Isabelle Treilleux, Thierry Walzer, Christophe Caux, Nathalie Bendriss-Vermare. The alarmin IL-33 is expressed in breast cancer: An emerging role in breast cancer immunity via the activation of NK cells? [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr B55.
Abstract B65: Alteration in cholesterol homeostasis and antibody synthesis in B cells an in-vivo effect of carcinogen (polyaromatic)
Authors: Saxena Nimisha , Kaur Amar Preet , Chandra Nimai Chand 
Published: March 2017

Abstract
Introduction: Cholesterol, a major ingredient of cellular growth, is maintained in the cells by either intracellular biosynthesis or LDL receptor mediated endocytosis. Various studies have shown increased LDLR and SREBP2 (transcription factor) expressions as well as intracellular saturation of cholesterol in malignant and proliferating cells.
Objectives: Citation of immune suppression is common in malignancy. B cells are antibody forming immune cells. Fate of Benzo-alpha-pyrene (mitogenic and carcinogenic doses) on B-cells has been aimed by exploring the role of cellular cholesterol homeostasis.
Methods: Intraperitoneal injection of carcinogen, classical mitogen and immunogen to Swiss Albino mice in groups for optimally effective dose, B-cell (CD19 & CD79a) counts by flowcytometry, ELISA for IgG estimation, western blot for protein expressions and spectrophotometry for cholesterol estimation were among the parameters studied.
Results: At immunosuppressive dose of Benzo-alphapyrene a significant decrease in serum IgG level, no significant change in number of B lymphocytes as compared with other agents, depressed expressions for LDLR / SREBP2 and significant decrease of cellular cholesterol (cytosolic and nuclear) were observed in mice model system.
Conclusion: Benzo-alphapyrene leads to decrease in LDLR and SREBP2 expression resulting insufficient total intracellular cholesterol level and thus affects B-cell to proliferate. Immunosupression becomes apparent, which allows carcinogen to stay in the system and generation of tumor elsewhere.
Citation Format: Nimisha Saxena, Sr., Amar Preet Kaur, Sr., Nimai Chand Chandra. Alteration in cholesterol homeostasis and antibody synthesis in B cells an in-vivo effect of carcinogen (polyaromatic). [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr B65.
Abstract IA06: Role of TCR specificity in regulatory T cell selection
Authors: Hsieh Chyi-Song 
Published: March 2017

Abstract
Regulatory T (Treg) cells play an important role in preserving self-tolerance and preventing autoimmunity. Because of this, Treg cells generate a natural barrier to immune mediated tumor rejection. Here, we will discuss the process of thymic education that generates a self-reactive Treg cell population which can suppress both autoimmune and anti-tumor responses. Treg cell selection in the thymus is primarily mediated by antigen-presenting cells (APCs) in the medulla, including medullary thymic epithelial cells (mTECs) that express the transcription factor Aire, as well as bone marrow (BM) APCs such as dendritic cells (DCs). Using TCR repertoire analysis of fixed TCRβ chain mice, we recently reported that BM APCs and mTECs make substantial contributions to negative and Treg cell selection. Interestingly, Aire-dependent TCRs were often dependent on BM APC antigen presentation, even though Aire expression itself is restricted to mTECs. Analysis of a selected set of Aire- and BM APC co-dependent TCRs suggests that Batf3-dependent CD8α+ DCs are the major BM APC subset responsible for co-operative antigen presentation. We will also discuss TCR repertoire analyses of Batf3/mice deficient in CD8α+ DCs, as well as potential mechanisms of antigen-transfer from mTECs to DCs and the implications on Treg cell recognition of self-antigens.
Citation Format: Chyi-Song Hsieh. Role of TCR specificity in regulatory T cell selection. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr IA06.
Abstract IA23: Personalizing cancer immunotherapy
Authors: Schreiber Robert D. 
Published: March 2017

Abstract
We previously showed that the immune system not only protects individuals against tumor outgrowth but also facilitates tumor escape by sculpting tumor cell immunogenicity, a process we called “Cancer Immunoediting”. We subsequently elucidated the mechanisms underlying cancer immunoediting, demonstrated the importance of tumor-specific mutant neoantigens as targets of this process, and translated our findings into cancer immunotherapies by showing that tumor-specific mutant neoantigens can be used to generate therapeutically effective personalized cancer vaccines against established tumors. We have since gone on to define the minimal antigenic requirements for therapeutically effective personalized cancer vaccines and documented the synergistic activity that neoantigen vaccines show when used in combination with current immunotherapies, chemotherapies and radiotherapy. Most recently we have developed evidence for a powerful immunodominance effect that occurs between different tumor antigens and have identified what appears to be a unique mechanism by which at least some forms of immunotherapies induce tumor specific destruction. These findings will be discussed.
Citation Format: Robert D. Schreiber. Personalizing cancer immunotherapy. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr IA23.