bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A116: IgG antibody switching and clonal expansion in melanoma and normal skin microenvironments
Authors: Saul Louise , Ilieva Kristina M. , Bax Heather J. , Karagiannis Panagiotis , Correa Isabel , Rodriguez-Hernandez Irene , Josephs Debra H. , Tosi Isabella , Egbuniwe Isioma U. , Lombardi Sara , Crescioli Silvia , Hobbs Carl , Villanova Federica , Cheung Anthony , Geh Jenny LC , Healy Ciaran , Harries Mark , Sanz-Moreno Victoria , Fear David , Spicer James F. , Lacy Katie E. , Nestle Frank O. , Karagiannis Sophia N. 
Published: November 2016

Abstract
Antibodies have been detected against known melanoma-associated antigens in patients with malignant disease. While much is known about cancer-specific T cell responses, the nature of cancer-specific B cells and their antibody repertoires are less well understood. We investigated circulating skin-homing B cells (CD19+CD22+CLA+) in healthy volunteers (n = 24) and melanoma patients (n = 49) and examined the presence of CD22+ B cells in melanoma lesions (n = 173) and normal skins tissue (n = 16). We detected mature IgG mRNA in 13 of 27 normal skin and 9 of 21 cutaneous melanoma samples and we detected mRNA for the enzyme Activation-induced cytidine deaminase (AID). IgG variable heavy chain sequences from melanomas (n = 51) and normal skins (n = 29) featured lower IgG1/IgGtotal subclass representation compared with circulating B cell antibody sequences (n = 36). The presence of affinity-matured cutaneous antibody repertoires in malignant skin was supported by evidence of somatic hypermutation, class-switching and B cell clonal family trees in melanoma lesions and a subset of melanoma-associated clones featuring shorter CDR3 region lengths relative to circulating B cell sequences. Homology modelling also indicated differential putative binding site patterns in melanoma compared to normal skin-resident antibodies, suggesting distinct melanoma-associated repertoires and potentially, antigen recognition profiles. These findings support the presence of a mature tumor-resident B cell compartment with characteristics distinct to that of B cells in normal skin and the circulation.
Citation Format: Louise Saul, Kristina M. Ilieva, Heather J. Bax, Panagiotis Karagiannis, Isabel Correa, Irene Rodriguez-Hernandez, Debra H. Josephs, Isabella Tosi, Isioma U. Egbuniwe, Sara Lombardi, Silvia Crescioli, Carl Hobbs, Federica Villanova, Anthony Cheung, Jenny LC Geh, Ciaran Healy, Mark Harries, Victoria Sanz-Moreno, David Fear, James F. Spicer, Katie E. Lacy, Frank O. Nestle, Sophia N. Karagiannis. IgG antibody switching and clonal expansion in melanoma and normal skin microenvironments [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A116.
Abstract A127: The role of macrophages in tissue homeostasis
Authors: Franklin Ruth A. , Pope Scott D. , Medzhitov Ruslan 
Published: November 2016

Abstract
Organisms maintain homeostasis at the cellular, tissue, and systemic levels in order to survive changing physiological and environmental conditions. While maintenance mechanisms at the cellular and systemic levels are well characterized, the key cell types and signaling components controlling homeostasis in tissue compartments are undefined. Perturbations in homeostasis activate stress response pathways and result in both cell-intrinsic and cell-extrinsic responses, the latter of which can result in tissue level adaptations. Macrophages are found in almost all tissues and are known to orchestrate tissue level responses to infection and damage. Furthermore, recent evidence suggests that these innate immune cells may also perceive more general and subtle changes within the surrounding environment. We hypothesize that macrophages regulate tissue level changes to maintain homeostasis and that this feature may become dysregulated during chronic inflammatory conditions, including cancer. In order to model disrupted homeostasis, we applied a number of diverse stressors to bone marrow-derived macrophages (BMDMs) in vitro: osmotic stress, endoplasmic reticulum (ER) stress, amino acid deprivation, glucose deprivation, hypoxia, and heat shock. Next, RNA sequencing at early and late time points was performed to compare gene expression patterns between different stress conditions. We found that each stressor induces a unique transcriptional program in BMDMs, as well as a set of genes shared amongst several stress conditions. To identify potential paracrine signals originating from macrophages and acting on surrounding tissues, we focused on genes encoding secreted proteins, upregulated early after stimulation under multiple conditions, and containing known stress-associated motifs in their promoters. We found that many of the genes fitting these criteria are associated with tissue remodeling, including extracellular matrix components, cell adhesion molecules, factors involved in angiogenesis, and chemokines/cytokines. We are currently developing both in vitro and in vivo models of tissue stress to investigate these molecules as potential regulators of tissue level homeostasis.
Citation Format: Ruth A. Franklin, Scott D. Pope, Ruslan Medzhitov. The role of macrophages in tissue homeostasis [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A127.
Abstract A132: Multi-parametric profiling of non-small cell lung cancers reveals distinct immunophenotypes
Authors: Lizotte Patrick , Ivanova Elena , Bittinger Mark , Wong Kwok-Kin 
Published: November 2016

Abstract
Immune checkpoint blockade improves survival in a subset of patients with non-small cell lung cancer (NSCLC), but robust biomarkers that predict response to PD-1 pathway inhibitors are lacking. Furthermore, our understanding of the diversity of the NSCLC tumor immune microenvironment remains limited. To develop a more comprehensive knowledge of the NSCLC tumor immune landscape, we performed comprehensive flow-cytometric immunoprofiling on both tumor and immune cells from 51 NSCLCs and integrated this analysis with clinical and histopathologic characteristics, next generation sequencing, mRNA expression, and PD-L1 immunohistochemistry (IHC). Cytometric profiling identified two main tumor immunophenotypes: an immunologically “hot” cluster with high abundance of CD8+ T cells expressing high levels of the inhibitory receptors PD-1 and TIM-3, and an immunologically “cold” cluster with lower relative abundance of CD8+ T cells and expression of inhibitory markers. The “hot” cluster was highly enriched for expression of genes associated with T cell trafficking and cytotoxic function by mRNA analysis, and high PD-L1 expression by IHC. Within the “hot” cluster there was a small subgroup with high granulocytic infiltrates and lower relative T cell abundance, but with high expression of inhibitory receptors by T cells. There was no correlation between immunophenotype and KRAS or EGFR mutation status, or patient smoking history, but we did observe an enrichment of squamous subtype and tumors with higher mutation burden in the “hot” cluster. Additionally, ∼20% of cases had high B cell infiltrates and we demonstrate that a subset of these cells display characteristics of immunosuppressive IL-10-producing cells. Our results support the use of immune-based metrics to study response and resistance to immunotherapy in lung cancer.
Citation Format: Patrick Lizotte, Elena Ivanova, Mark Bittinger, Kwok-Kin Wong. Multi-parametric profiling of non-small cell lung cancers reveals distinct immunophenotypes [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A132.
Abstract A137: PD-L1 antibodies induce macrophage phenotypic and functional activation
Authors: Hartley Genevieve , Wheat William , Coy Jonathan , Dow Steven 
Published: November 2016

Abstract
Background: The ability of PD-L1 signaling to alter tumor metabolism and stem cell properties has been previously established. However, the effects of PD-L1 signaling on other cells that express PD-L1, including tumor-associated macrophages, has not been previously investigated. It is also unknown how treatment with PD-L1 targeted antibodies may affect macrophage function.
Purpose: These studies were designed to investigate the effects of PD-L1 antibodies on macrophage phenotype and function. Studies were done using in vitro assays of murine bone marrow-derived macrophages, as well as human monocyte-derived macrophages.
Experimental Methods: Murine bone marrow-derived macrophages were generated by non-adherent culture in M-CSF. The cells were then plated in tissue culture plates and incubated with anti-murine PD-L1 antibodies (or with isotype-matched antibodies), and the effects on macrophage phenotype, proliferation, activation, antigen presentation, and tumor killing were assessed.
Study Results: Following incubation with PD-l1 antibodies, we observed remarkable phenotypic changes in bone marrow-derived macrophages. These included physical changes including increased cell size and spreading, and increased proliferation and survival as measured by EdU incorporation and MTT assay. Macrophages incubated with PD-L1 antibodies spontaneously upregulated production of inflammatory cytokines and upregulated co-stimulatory molecule expression, as assessed by flow cytometry. Increased functional activation was revealed by upregulated expression of iNOS and decreased antigen uptake.
Conclusions: Our findings indicate that PD-L1 antibodies induce strong activation of macrophages in vitro. These findings suggest that some of the observed immunological activities of PD-L1 therapeutic antibodies may be mediated by macrophage activation.
Citation Format: Genevieve Hartley, William Wheat, Jonathan Coy, Steven Dow. PD-L1 antibodies induce macrophage phenotypic and functional activation [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A137.
Abstract A139: Antitumor effects of improved DC vaccine with ALA-PDT induced immunogenic apoptotic cells for skin squamous cell carcinoma in mice
Authors: Zhang Haiyan , Zhang Guolong , Fan Zhixia , Wang Xiaojie , Shi Lei , Yang Degang , Bahavar Cody F. , Zhou Feifan , Chen Wei R. , Wang Xiuli 
Published: November 2016

Abstract
Targeted immunotherapy using dendritic cell (DC) vaccine has been employed for the treatment of solid tumors. Topical 5-aminolevulinic acid mediated photodynamic therapy (ALA-PDT), an established approach for topical cancers, can induce an effective antitumor immune response.We have previously shown that ALA-PDT-induced tumor lysates could considerably enhance antigen-presenting capacity of ex vivo-generated DCs.The current study further demonstrates that ALA-PDT-DC vaccine can induce immune responses against cancers.DC cells pulsed by PDT-treated cutaneous squamous cell carcinoma (cSCC) cells inhibited SCC to a greater extent than tumor lysates treated by PDT alone or DCs pulsed by freeze/thawed treated tumor cells (FT-DC).Immunohistochemistry showed that PDT-DC vaccine could increase the activity of CD4+ and CD8+ T cells in the tumor implantation sites.Flow cytometry assays showed that CD4+ and CD8+ T cells in the spleens of PDT-DC vaccine immunized mice increased significantly.Furthermore, we observed increased amounts of IL-12 and IFN-γ and decreased amounts of IL-10 in the splenocytes and peripheral blood of PDT-DC vaccine immunized mice by ELISA.Taken together, our findings suggest that PDT-DC vaccination is an effective prophylactic therapy for cSCC.
Note: This abstract was not presented at the conference.
Citation Format: Haiyan Zhang, Guolong Zhang, Zhixia Fan, Xiaojie Wang, Lei Shi, Degang Yang, Cody F. Bahavar, Feifan Zhou, Wei R. Chen, Xiuli Wang. Antitumor effects of improved DC vaccine with ALA-PDT induced immunogenic apoptotic cells for skin squamous cell carcinoma in mice [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A139.
Abstract B006: Large scale microarray profiling reveals four stages of immune escape in Non Hodgkin lymphomas
Authors: Fournie Jean-Jacques 
Published: November 2016

Abstract
Non-Hodgkin B-cell lymphoma (B-NHL) are aggressive lymphoid malignancies that develop in patients due to oncogenic activation, chemo-resistance and immune evasion. Tumor biopsies show that B-NHL frequently use several immune escape strategies, which has hindered the development of checkpoint blockade immunotherapies in these diseases. To gain a better understanding of B-NHL immune editing, we hypothesized that the transcriptional hallmarks of immune escape associated with these diseases could be identified from the meta-analysis of large series of microarrays from B-NHL biopsies. Thus, 1446 transcriptome microarrays from seven types of B-NHL were downloaded and assembled from 33 public Gene Expression Omnibus (GEO) datasets, and a method for scoring the transcriptional hallmarks in single samples was developed. This approach was validated by matching scores to phenotypic hallmarks of B-NHL such as proliferation, signaling, metabolic activity and leucocyte infiltration. Through this method, we observed a significant enrichment of 33 immune escape genes in most diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) samples, with fewer in mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL) samples. Comparing these gene expression patterns with overall survival data evidenced four stages of cancer immune editing in B-NHL: non-immunogenic tumors (stage 1), immunogenic tumors without immune escape (stage 2), immunogenic tumors with immune escape (stage 3), and fully immuno-edited tumors (stage 4). This model complements the standard international prognostic indices for B-NHL and proposes that immune escape stages 3 and 4 (76% of the FL and DLBCL samples in this dataset) identify patients relevant for checkpoint blockade immunotherapies.
Note: This abstract was not presented at the conference.
Citation Format: Jean-Jacques Fournie. Large scale microarray profiling reveals four stages of immune escape in Non Hodgkin lymphomas [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B006.
Abstract B009: Phase I clinical trial of a PSA, IL-2, GM-CSF containing prostate cancer vaccine in PSA defined biochemical recurrent prostate cancer patients
Authors: Head Jonathan F. , Daniels Gregory A. , McKinney Michelle , Ongkeko Weg , Sakamoto Kyoko , Wang-Rodriguez Jessica 
Published: November 2016

Abstract
Immunotherapy for cancer has had two main approaches that have led to clinical applications. The first is stimulating immune responses to tumor cells with cytokines or cellular immunotherapy and the second is blocking tumor immune evasion and the associated inhibition of T-cell activation with antibodies to the CTLA-4 receptor, PD-1 receptor or PD-L1. We have taken a different approach and have developed therapeutic cancer vaccines that are a combination of tumor antigens (proteins overexpressed by tumors) with biological adjuvants (the cytokines IL-2 and GM-CSF). This study is a Phase 1a/1b clinical trial of a PSA/IL-2/GM-CSF vaccine in recurrent prostate cancer in hormone-naïve and hormone-independent patients. Major inclusion criteria include adenocarcinoma of the prostate, rising serum PSA and no measurable disease. Phase 1a examines the rate of dose limiting adverse events (DLAEs) in an initial course of 6 vaccinations (“induction vaccination”). Twenty patients will receive intradermal injections of the PSA/IL-2/GM-CSF vaccine at weeks 0, 1, 2, 6, 10 and 14. To date, twelve patients in the Phase 1a portion of the trial have received all 6 vaccines. Eight of the 11 patients who have received all 6 vaccines had increased immune responses to PSA in a lymphocyte blastogenesis assay by week 19. Six of 10 of the patients had an increase in the doubling time of their serum PSA, suggesting a slowing of the progression of the cancer. Median follow up after the first vaccine is 23 months (range: 4-32 months). None of the patients vaccinated in the Phase 1a portion have had a DLAE and enrollment continues in the Phase 1a.
Citation Format: Jonathan F. Head, Gregory A. Daniels, Michelle McKinney, Weg Ongkeko, Kyoko Sakamoto, Jessica Wang-Rodriguez. Phase I clinical trial of a PSA, IL-2, GM-CSF containing prostate cancer vaccine in PSA defined biochemical recurrent prostate cancer patients [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B009.
Abstract B012: Preclinical study of Kiatomab, a novel monoclonal antibody to the cancer stem cell surface marker KIAA1114, for anti-cancer therapy in colorectal carcinoma
Authors: Kim Young Min , Kim Sae Won , Lee Seungwon , Kim Hyekang , Kim Ji-Hae , Park Han Wook , Sung Young Chul , Lee Seung-Woo 
Published: November 2016

Abstract
Most targeted therapy drugs block the growth of cancer cells by targeting specific molecules needed for tumor growth. Among targeted therapy drugs, cetuximab, the monoclonal antibody which binds to epidermal growth factor receptor (EGFR) and inhibits downstream signaling of EGFR, has greatly improved the median survival of patients with metastatic colorectal cancer (CRC). Yet, cetuximab showed limited therapeutic effect in CRC patients who carry certain mutation in the KRAS, which emphasizes the necessity of developing new targeted therapy drugs for CRC. KIA1114 is a full-length protein of the trophinin gene and is localized on the cell surface. In our previous research, we identified the role of KIA1114 as a novel surface marker of tumor initiating cells of hepatocellular carcinoma (HCC) by developing Kiatomab, KIA1114-specific monoclonal antibody. Here, we show that KIA1114 is also highly expressed in various CRC cells with mouse or human origin. Kiatomab treatment inhibits tumor growth in a syngeneic graft CRC mouse model in antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) dependent manner. In the metastatic CRC model, Kiatomab therapy suppresses metastasis, with a significant increase of survival. Of note, the anticancer efficacy of Kiatomab is further improved by combinatorial treatment with the standard chemotherapeutic agent cyclophosphamide (CTX), in both metastatic and solid tumor models. In summary, our findings suggest that KIAA1114 is a new target for CRC and its monoclonal antibody Kiatomab might have a potential for anticancer therapy.
Citation Format: Young Min Kim, Sae Won Kim, Seungwon Lee, Hyekang Kim, Ji-Hae Kim, Han Wook Park, Young Chul Sung, Seung-Woo Lee. Preclinical study of Kiatomab, a novel monoclonal antibody to the cancer stem cell surface marker KIAA1114, for anti-cancer therapy in colorectal carcinoma [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B012.
Abstract B015: Expansion and activation of CD103+ dendritic cell progenitors at the tumor site transform tumor response to PD-L1 and BRAF inhibition
Authors: Salmon Hélène , Idoyaga Juliana , Rahman Adeeb , Remark Romain , Gnjatic Sacha , Bhardwaj Nina , Brody Joshua , Palucka Anna Karolina , Ginhoux Florent , Merad Miriam 
Published: November 2016

Abstract
High numbers of melanoma lesions develop resistance to BRAF blockade or fail to respond to checkpoint inhibition therapy. Here we explored whether modulation of intratumoral antigen presenting cells (APCs) can help increase response to BRAF and checkpoint blockade in tamoxifen-induced Braf-mutant and B16 melanoma lesions. In both models, we found that CD103+ dendritic cells (DCs) were the only APCs that transported intact antigens to the lymph nodes and primed tumor-specific CD8+ T cells.
CD103+ DC expressed high PD-L1 levels in the tumor and were required to promote anti-tumoral effects upon blockade of the checkpoint ligand PD-L1; however, PD-L1 inhibition only led to partial responses and minimal accumulation of intratumoral CD8+ T cells. Strikingly, systemic administration of fms-like tyrosine kinase 3 ligand (Flt3L) followed by intratumoral poly I:C injections expanded and activated CD103+ DC progenitors in the tumor, enhancing responses to BRAF and PD-L1 blockade and protecting mice from tumor rechallenge in a T cell dependent manner. Thus, the paucity of activated CD103+ DCs in tumors limits checkpoint blockade efficacy and Flt3L-poly I:C therapy can transform clinical responses to checkpoint and BRAF blockade.
Salmon et al, 2016. Immunity, 44(4):924-38.
Citation Format: Hélène Salmon, Juliana Idoyaga, Adeeb Rahman, Romain Remark, Sacha Gnjatic, Nina Bhardwaj, Joshua Brody, Anna Karolina Palucka, Florent Ginhoux, Miriam Merad. Expansion and activation of CD103+ dendritic cell progenitors at the tumor site transform tumor response to PD-L1 and BRAF inhibition [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B015.