bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3834: Plasmablastic lymphoma provisional prognostic score
Authors: Haddad Philip A. , Lerner Jaren 
Published: March 2024

Abstract
Background Plasmablastic Lymphoma (PBL) is a rare and aggressive subtype of non-Hodgkin's lymphoma. It tends to be associated with immunosuppressive clinical contexts, such as HIV infection and immunosuppressive therapies for autoimmune disorders and organ transplants. However, due to the rarity of the disease, which needs to be better understood, varied treatment approaches have been implemented, and no optimal data or guidelines for managing PBL are available. Therefore, we conducted this study to develop a provisional PBL prognostic score (PBLPS) for this rare disease.
Methods We used our constructed PBL database, which contains retrospective data on 300 cases. Such data included demographics such as sex, age, and race. It also included disease presentation symptoms, duration of symptoms before diagnosis, site(s) of the disease, blood counts, coexisting comorbidities, disease immunohistochemical and molecular phenotype, types of treatment, and survival outcomes. Of the 300 cases, 291 had complete survival and outcomes data, the sample chosen for this study. Cox proportional-hazards model and Log-rank tests were used to assess the influence of clinicopathologic factors on overall survival (OS). We included factors that statistically impacted OS and scored them by the impact of their hazard ratios.
Results The median OS of the cohort was 25 months. The following dichotomous variables were identified as impactful prognostic factors in this cohort: LDH&gt;500 (p=0.04), CD4&lt;100 (p=0.006), bone marrow (BM) involvement (p&lt;0.0001), EBER-negative (p=0.01), HHV8+ (p=0.02), and involvement of liver (p=0.003), lungs/pleura (p&lt;0.0001), and upper GI tract (p=0.001). A prognostic model was devised using these variables to identify different levels of risk. Involvement of BM and involvement of any of the worse prognosis organs (liver, lung/pleura, and/or upper GI tract) were each assigned a score of 2 when present. CD4&lt;100, EBER-negative, and LDH&gt;500 were assigned 1 point each as they had the lowest hazard ratios of all the other variables. In this exploratory cohort, we assigned low risk a score of 0, intermediate risk a score of 1-2, and high risk a score of 3-7. This prognostic score system led to our cohort's most optimal risk discriminatory model, where low, intermediate, and high risk had a median OS of NR, 15, and 4 months, respectively (p&lt;0.0001).
Conclusion This PBLPS is a promising new tool for risk-stratifying patients with PBL. However, it still requires prospective validation.
Citation Format: Philip A. Haddad, Jaren Lerner. Plasmablastic lymphoma provisional prognostic score [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3834.
Abstract 3836: Mast cell leukemia provisional prognostic score
Authors: Haddad Philip A. , Chennapragada Sumasri 
Published: March 2024

Abstract
Background Mast cell leukemia (MstCL) is a rare but aggressive variant of systemic mastocytosis (SM), defined by the presence of &gt;20% atypical mast cells in the bone marrow. It is further classified into leukemic and aleukemic variants based on the presence or absence of &gt;10% atypical mast cells in the peripheral blood, respectively. There is a wide variation in treatment regimens used to treat MstCL. Despite this, prognosis remains poor. While MstCL often follows an aggressive course, its outcomes vary considerably. We conducted this study to develop a provisional MstCL prognostic score (MCLPS) for this rare disease.
Methods We used our constructed MstCL database, which contains retrospective data on 144 cases. Such data included demographics such as sex, age, and race. It also included disease presentation symptoms, duration of symptoms before diagnosis, site(s) of the disease, blood counts, coexisting comorbidities, disease immunohistochemical and molecular phenotype, types of treatment, and survival outcomes. Of the 144 cases, only 104 had complete survival and outcomes data, the sample chosen for this study. Cox proportional-hazards model and Log-rank tests were used to assess the influence of clinicopathologic factors on overall survival (OS). We included factors that statistically impacted OS and scored them by the impact of their hazard ratios.
Results The median OS of the cohort was 9 months. The following dichotomous variables were identified as impactful prognostic factors in this cohort: Age&lt;55 (6 vs. 15 months), Hgb&lt;10g/dl (3 vs. 29 months), Plt&lt;100K (3 vs. 23 months), leukemic phase (7 vs. 18 months), and complex cytogenetics (2.3 vs. 23 months). A prognostic model was devised using these variables to identify different levels of risk. Each variable was assigned a score of 1 when present for a maximum possible score of 5. In this exploratory cohort, low risk was assigned a score of 0, intermediate risk a score of 1-2, and high risk a score of 3-5. This prognostic score system led to our cohort's most optimal risk discriminatory model, where low, intermediate, and high risk had a median OS of 29, 8, and 2.4 months, respectively (p=0.0006).
Conclusion This MCLPS is a promising new tool for risk-stratifying patients with MstCL. However, it still requires prospective validation.
Citation Format: Philip A. Haddad, Sumasri Chennapragada. Mast cell leukemia provisional prognostic score [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3836.
Abstract 3857: Tumor-extrinsic BIRC3 promote sensitivity to checkpoint inhibition immunotherapy in breast cancer
Authors: Yang Dejuan , Sun Jiazheng , Ren Guosheng , Li Hongzhong 
Published: March 2024

Abstract
Baculoviral IAP repeat containing 3 (BIRC3) protein play a critical role in breast cancer. Blocking BIRC3 cause apoptosis in tumor cells, but its correlation with tumor immunity remains elusive. TCGA databases were employed to examine the expression of BIRC3 in breast cancer. The correlation between BIRC3 expression and T cell infiltration and function was employed in breast cancer tissues (n=92) by immunohistochemistry. Birinapant, a selective BIRC3 inhibitor, was then used to investigate the effect of BIRC3 blockade on tumor immune microenvironment (TIME) landscape of breast cancer syngeneic mouse models by flow cytometry. Survival analysis suggested that the low expression of BIRC3 was associated with poor overall survival (OS). Additionally, we uncovered the close association between BIRC3 expression and the profiles of immune cells in breast cancer microenvironment based on the TCGA dataset. Interestingly, we found that BIRC3 expression was positively correlated with cytotoxic T lymphocyte infiltration and T-cell effector function by immunohistochemistry. The in vivo experiments suggested that blocking BIRC3 might convert ‘hot’ tumor into ‘cold’ tumor, which was characterized by a decreased of CD8+ T cell infiltration and inhibition of CD8+T cell function. Furthermore, we observed that BIRC3 blocking combined with immune checkpoint blockade therapy (ICT) greatly restrains immunotherapy efficacy of breast cancer model. Our study revealed a positively association between BIRC3 and anti-tumor immune landscape in breast cancer. Notably, we established a validated prognosis model based on BIRC3 and BIRC3 associated immunomodulators in breast cancer.
Citation Format: Dejuan Yang, Jiazheng Sun, Guosheng Ren, Hongzhong Li. Tumor-extrinsic BIRC3 promote sensitivity to checkpoint inhibition immunotherapy in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3857.
Abstract 3877: Multi-modal analysis of paracrine signaling in group 3/4 medulloblastoma
Authors: Yu Bohyeon , Jung Jangham , Diaz Aaron 
Published: March 2024

Abstract
Medulloblastoma (MB) is the most common primary brain malignancy in kids, with the group 3 and 4 subtypes (G3/4) being the most aggressive. Recent single-cell genomics studies have identified the G3/4 MB cell of origin and point to disrupted stem-cell differentiation as a key factor in MB pathogenesis. However, surprisingly little is known about the contribution of tumor-supportive paracrine signaling to the ontogeny of this disease. The spatial organization of MB cellular hierarchies is not completely understood. We profiled N=24 G3/4 MBs from UCSF patients via single-nucleus RNA sequencing (snRNA-seq). Of these cases, N=10 were profiled via single-cell assay for transposase-accessible chromatin by sequencing (scATAC-seq). To capture the spatial context, we profiled an additional 20 samples via spatial transcriptomics using the Visium and Xenium platforms. We found that the standard Xenium brain capture set was inadequate, and we developed a highly specific capture set for G3/4 MBs. In particular, our panel resolves cell-type differences in the stage of MB lineage commitment, from rhombic-lip progenitors to more differentiated unipolar brush-like cells. Altogether, over 110,000 nuclear-sequencing libraries and over 1,898,000 spatially-resolved single-cell libraries were generated. We inferred cell-cell communication signals from our snRNA-seq data by identifying co-expressed receptors and their cognate ligands. We then performed an integrated analysis of our snRNA-seq and scATAC-seq data to infer the cis-regulatory enhancers of those signaling genes, as well as the transcription factors that bind them. We employed our spatial transcriptomics data to confirm paracrine signaling networks inferred from nuclear-sequencing data. We found that distinct MB cell types corresponding to different stages of differentiation occupied specific spatial domains. The results of our ongoing analysis of this spatially-resolved single-cell atlas will be presented. This study paves the way for innovative therapeutic strategies targeting paracrine signaling in G3/4 MB.
Citation Format: Bohyeon Yu, Jangham Jung, Aaron Diaz. Multi-modal analysis of paracrine signaling in group 3/4 medulloblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3877.
Abstract 392: MYB regulates a specific subset of hypoxia-induced genes and exhibits altered genomic occupancy under hypoxia
Authors: Anand Shashi , Khan Mohammad Aslam , Vikramdeo Kunwar Somesh , Singh Seema , Singh Ajay Pratap 
Published: March 2024

Abstract
Hypoxia, an unavoidable microenvironmental stress, greatly influences the tumor cell behavior and therapeutic outcomes. Under low oxygen condition, tumor cells undergo transcriptional reprogramming, largely mediated through hypoxia-inducible factors (HIFs), triggering adaptive response pathways. We recently demonstrated a significant role of MYB in hypoxic survival of pancreatic cancer cells by facilitating adaptive changes in cellular metabolism in collaboration with HIF1α. Here, we employed genome-wide deep sequencing approaches to study the impact of hypoxia on transcriptional reprogramming of pancreatic cancer cells and investigate the role of MYB in the hypoxia-dependent processes. A large number of differentially expressed genes (DEGs) were identified in pancreatic cancer cells subjected to hypoxia (1% O2) and associated with multiple adaptive response pathways. Specifically, we found that pathways related to autophagy, cell migration, epithelial-to-mesenchymal transition, endocytosis, cytoskeleton reorganization were induced, while those associated with RNA processing, ribosome biogenesis, DNA replication and cell cycle were suppressed. To analyze the role of MYB in these adaptive responses, we compared the relative abundance of transcripts in MYB-overexpressing control and MYB knockout (KO) pancreatic cancer cells when cultured under normoxic or hypoxic conditions. We observed that the transcriptional output of MYB was drastically changed under hypoxia with a vast majority of genes being distinctly altered in response to the loss of MYB expression under normoxia and hypoxia. To examine if it resulted from altered genomic occupancy of MYB under normoxia and hypoxia, we compared MYB ChIP-seq peaks under these conditions. We observed a decrease in overall MYB-bound genomic regions under hypoxia despite the fact that we did not observe a decrease in nuclear MYB expression. More interestingly, the genomic occupancy of MYB shifted substantially from regions proximal to transcription start site to distal intergenic or intronic regions under hypoxia. Studies are currently underway to examine the mechanisms underlying the altered MYB genomic occupancy and its impact on adaptive physiological response of pancreatic cancer cells under hypoxia. Together, our findings bring unprecedented insight into the mechanistic role of MYB in hypoxia adaptation and pancreatic cancer pathobiology.
Citation Format: Shashi Anand, Mohammad Aslam Khan, Kunwar Somesh Vikramdeo, Seema Singh, Ajay Pratap Singh. MYB regulates a specific subset of hypoxia-induced genes and exhibits altered genomic occupancy under hypoxia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 392.
Abstract 3922: Quaking modulates anti-tumor immunity by regulating antigen processing and presentation in dendritic cells
Authors: Li Yating , Hu Jian , Yee Cassian 
Published: March 2024

Abstract
Dendritic cells are essential players in anti-tumor immunity. One of their critical roles is to process and present tumor associated antigens to T cells, thereby inducing antigen-specific T cell response. However, cellular factors and molecular pathways regulating antigen processing and presentation by DCs are not fully understood.Here, we revealed a potential regulatory role of a transcriptional co-activator, Quaking (QKI), and its binding partner, PPARδ in antigen processing and presentation by DCs. Consistent with our previous studies in neural stem cells and microglia, we found QKI and PPARδ enhance phagocytosis in DCs by upregulating genes involved in the formation of phagosome and endosomes. QKI- or PPARδ-deficient DCs showed reduced CD8+ T cell priming capacity in vitro. In vivo tumor models suggested DC-specific knocking out of QKI or PPARδ promoted the tumor growth. Furthermore, ablation of QKI or PPARδ in DCs limited the effectiveness of immune checkpoint blockade in multiple tumor models.Together, these revealed a transcriptional regulation of antigen processing and presentation by DCs through QKI and PPARδ. Our data also suggested that perturbing this important function of DC would subvert their anti-tumor activity, highlighting the pivotal role of DCs in an effective anti-tumor immune response.
Citation Format: Yating Li, Jian Hu, Cassian Yee. Quaking modulates anti-tumor immunity by regulating antigen processing and presentation in dendritic cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3922.
Abstract 3947: Non-BRCA variants in hereditary breast and ovarian cancer patients in the Northern Mexico population
Authors: Burciaga-Flores Carlos H. , Perez-Ibave Diana C. , Garza-Rodriguez Maria L. , Vidal-Gutierrez Oscar , Villarreal-Garza Cynthia M. , Mendez Dione Aguilar y 
Published: March 2024

Abstract
Background: Hereditary cancer syndromes explain 5-10% of all cancer cases. Germline pathogenic variants in BRCA1 and BRCA2 genes (BRCA) are present in 2-3% of all breast cancer (BC), and 15% of all ovarian cancer (OC) cases. BRCA1 and BRCA2 pathogenic variants (PV) represent 25-28% of BC and 40% of OC patients with a positive familial history. BRCAs are the most studied genes for the prevalence, family history, preventive surgeries, and target treatment options in both BC and OC. There are other genes, important in the diagnosis, pathogenesis, and treatment options of the patients: TP53, PALB2, CHEK2, among others. This study aims to identify the prevalence of non- BRCA genes related to the development of hereditary breast and ovarian cancer syndrome in patients of Northeast Mexico.
Methods: This is a multicenter study that recruited patients from two reference oncology centers in Nuevo Leon, Mexico: the CECIL (The CUCC Early Cancer Detection Clinic) Hereditary Cancer Registry and Hereditary Cancer Program from Tec Salud. From March of 2016 to March of 2023, a total of 872 patients meeting NCCN criteria were evaluated by Medical Geneticists from both centers and were tested with NGS multigene cancer panels.
Results: A total of 665 (76.26%) patients with a clinical diagnosis of HBOC (Hereditary Breast Hereditary Cancer Syndrome) were included. We found 310 (46.6%) patients had at least one variant, 180 (58%) with at least one pathogenic variant, and 130 (41%) with a VUS (a variant of uncertain significance). BRCA1 was found in 79 (43.8%) and BRCA2 in 32 (17.7%) of all PV. Non-BRCA PV were found in 69 (38.3%) patients: 4 ATM, 2 BLM, 3 BRIP1, 22 CHEK2, 4 CDKN2A, 5 MUTYH, 10 PALB2, 4 RAD51C, 2 SDHA, 2 TP53, 2 WRN, CDH1, CDK4, DICER, MSH3, NBN, PTEN, RAD50, USH2A one of each. Is remarkable that 19 of the 22 patients with CHEK2 and 5 of the 10 patients with PALB2 had the recurrent PV c.707T&gt;C and c.2167_2168del, respectively.
Conclusions: Non-BRCA PV in Northern Mexico corresponds to one-third of the BC and OC cases, including HRD (homologous recombination deficiency) genes. HDR patient carriers are potential targets of iPARP therapies. This project reinforces the fact that multigene panels should be employed to ensure a complete diagnosis in hereditary cancer patients.
Citation Format: Carlos H. Burciaga-Flores, Diana C. Perez-Ibave, Maria L. Garza-Rodriguez, Oscar Vidal-Gutierrez, Cynthia M. Villarreal-Garza, Dione Aguilar y Mendez. Non-BRCA variants in hereditary breast and ovarian cancer patients in the Northern Mexico population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3947.
Abstract 3964: A cancer survival program against activated T cell attack
Authors: Wang Michael X. , Mauch Brandon E. , Williams August F. , Barazande-Pour Tania , Hoffmann Filipe Araujo , Harris Sophie H. , Lathrop Cooper P. , Turkal Claire E. , Paw Michelle H. , Gervasio David A. , Tran Tiffany , Guo Theresa , Daniels Gregory A. , Park Soo J. , Hangauer Matthew J. 
Published: March 2024

Abstract
The immune-cancer interactions downstream of immune checkpoint inhibition present the next targetable interface of cancer immunity. Despite evidence for cytotoxic T lymphocyte (CTL) infiltration and cytolytic activity within immunotherapy-responsive tumors, partial responses and acquired resistance are common, indicating additional barriers for complete tumor elimination. We report a survival program engaged within residual cancer cells exposed to weeks of activated CTLs. Contrary to immune-evasion mechanisms, we observe a residual antigenic cancer cell subpopulation which activates CTLs, survives within IFNγ-high environments, and withstands CTL-induced apoptosis. This cancer survival program, termed immune-induced persistence, is reversibly-driven (non-genetic) and prevents the complete CTL-mediated elimination of cancer cell populations by supporting the survival of quiescent cancer ‘persister’ cells against activated CTL attack. Persister cells display sublethal caspase activity and caspase-dependent DNA damage, consistent with CTL-induced genomic instability, and depend on the inhibitors of apoptosis proteins for survival. Notably, immune-induced persistence presents a markedly distinct survival program than drug-induced persistence, including distinctive apoptotic profiles, stress response pathways, and vulnerabilities. Thus, cancer cell populations can transiently adopt non-redundant survival programs in response to various cytotoxic environments. Features of immune-induced persistence are observed within CTL-treated human cancer cell lines, immune-treated human tumor slice cultures, and intratumor transcriptional heterogeneity programs. Under continued CTL exposure, persistent cancer populations give rise to genetically distinct cancer clones, including stably resistant immune escape variants, modeling acquired resistance to cancer immunotherapies. We propose sublethal interactions between effector immune cells and cancer persister cells as a critical and targetable variable at the interface between activated immunity and cancer.
Citation Format: Michael X. Wang, Brandon E. Mauch, August F. Williams, Tania Barazande-Pour, Filipe Araujo Hoffmann, Sophie H. Harris, Cooper P. Lathrop, Claire E. Turkal, Michelle H. Paw, David A. Gervasio, Tiffany Tran, Theresa Guo, Gregory A. Daniels, Soo J. Park, Matthew J. Hangauer. A cancer survival program against activated T cell attack [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3964.