bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1520: A novel cluster of cytolytic alpha/beta TCR+CD4−CD8−T cells originating from CD8+T cells with potent innate-like T cell killing ability: implicating adoptive T cell transfer therapy for hepatocellular carcinoma
Authors: Wu Cheng-Heng , Tseng Te-Wei , Huang Chen-Yang , Ou Ping-Hsun , Lin Yi-Chen , Chen Pin-Jung , Lin Po-Ting , Yang Chan-Keng , Teng Wei , Wu Tsung-Han , Lin Yung-Chang , Lin Chun-Yen 
Published: March 2024

Abstract
Tumor immunotherapies represent promising strategies for treating various cancers, including hepatocellular carcinoma. In this context, immune cells, including the adoptive T cell transfer treatment, become the focus of interests. Notably, alpha/beta TCR+CD4−CD8−T (DNT) cells is a subgroup of T cells that is ignored for a long time but was re-focused recently. These DNT cells are a group of cells with opposite functions in different condition, including pro-inflammatory or suppressive functions and possibly originated from over-stimulation of peripheral CD4+T cells/CD8+T cells or a special group of T cells formed in thymus. In our research results, we have found these DNT cells increased in murine hepatoma model, especially in the tumor microenvironment. In addition, these DNT cells from tumor microenvironment of murine hepatoma possessed potent tumor-killing ability. Furthermore, we analyzed the transcriptome profile of T cells in tumor microenvironment by single cell RNAseq approach (CITE-seq). We found DNT cells could be categorized into two main clusters, one is cytolytic DNT cells, resemble the potent CD8+T cells, and another is the CD4+T cell-like DNT cells. These cytolytic DNT cells are not exhausted but with high expression of cytolytic molecule and low hypoxia-inducible factor-1alpha (HIF-1a) expression. By trajectory analysis, cytolytic DNT cells come from the conventional CD8+T cells but following a unique developmental pathway that is different from the exhausted CD8+T cells. Interesting, these cytolytic DNT cells also expressed high level of Fcer1g molecule, a marker of innate CD8+T cells. In addition, these DNT cells could be generated and expanded in-vitro by IL-15 without TCR activation. In conclusion, we identified a cluster of cytolytic DNT cells, originated from CD8+T cells, exhibits innate T cells behavior and potent killing ability. In addition, these cytolytic DNT cells could be generated and expanded in-vitro for the adoptive T cell transfer treatment of hepatoma.
Citation Format: Cheng-Heng Wu, Te-Wei Tseng, Chen-Yang Huang, Ping-Hsun Ou, Yi-Chen Lin, Pin-Jung Chen, Po-Ting Lin, Chan-Keng Yang, Wei Teng, Tsung-Han Wu, Yung-Chang Lin, Chun-Yen Lin. A novel cluster of cytolytic alpha/beta TCR+CD4−CD8−T cells originating from CD8+T cells with potent innate-like T cell killing ability: implicating adoptive T cell transfer therapy for hepatocellular carcinoma [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 1520.
Abstract 1535: Differential immune microenvironments in triple-negative breast cancer and hormone receptor-positive HER2-negative breast cancer: A spatial analysis via multiplex immunofluorescence
Authors: Cha Yoon Jin , Park Inho , Shin Su-Jin 
Published: March 2024

Abstract
Objective: To elucidate differences in immune cell (IC) composition and their spatial distribution between triple-negative breast cancer (TNBC) and hormone receptor-positive HER2-negative breast cancer (HR+HER2-BC), and to evaluate the effect of PD-L1 status on these parameters.
Methods: We selected 32 patients with ≥60% tumor-infiltrating lymphocytes (TIL) (TNBC, n=18; HR+HER2- BC, n=14). Multiplex immunofluorescence was employed on resected tumor tissues. Using markers such as CK, CD20, CD8, CD4, and FOXP3, IC types and tumor cells (TC) were identified in both stromal and tumor areas. We analyzed and compared cellular density and proportional distribution of IC, and spatial interactions (both IC-TC and IC-IC) based on tumor subtype and PD-L1 status.
Results: TNBC exhibited a unique IC composition with a higher proportion of CD8+IC (stroma: 27% vs 17%, p&lt;0.001; tumor: 54% vs 31%, p&lt;0.001) and CD4+FOXP3+IC (stroma: 3.9% vs 3.0%, p=0.036) than HR+HER2-BC. Among PD-L1 positive cases, TNBC had a denser stromal population of CD4+FOXP3+IC (146.4±67.1/mm2 vs 114.3±146.9/mm2, p=0.036). Both tumor subtypes displayed varied IC compositions based on PD-L1 status. Density plots revealed a pronounced clustering of IC near TC in TNBC, especially in PD-L1 positive cases. Analysis of cell-cell interactions showed diverse adjacency patterns between TC and various IC combinations with frequencies differing by tumor subtype and PD-L1 status.
Conclusion: The immune landscape, typified by IC composition and spatial distribution, varies between TNBC and HR+HER2- BC, with PD-L1 status further modulating these patterns.
Citation Format: Yoon Jin Cha, Inho Park, Su-Jin Shin. Differential immune microenvironments in triple-negative breast cancer and hormone receptor-positive HER2-negative breast cancer: A spatial analysis via multiplex immunofluorescence [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 1535.
Abstract 1551: Succinyl-CoA synthetase Beta-A: A novel metastasis promoting factor in lung cancer
Authors: Kang Jihoon , Hwang Jung Seok , Boese Austin C. , Shuff Sydney , Kim Jaehyun , Eun Kiyoung , Kang Sumin 
Published: March 2024

Abstract
Changes in metabolism occur when cancer cells disseminate from primary sites and metastasize. Mitochondrial metabolism plays an essential role in various biological processes of cancer cells, but the underlying mechanism through which mitochondrial factors contribute to cancer metastasis remains largely elusive. Anoikis is a form of apoptosis induced by loss of cell adhesion, and metastatic tumor cells must be anoikis resistant to survive during circulation before forming metastatic foci in distant organs. We performed an unbiased RNAi screen using a customized mitochondrion shRNA library and identified succinyl-CoA synthetase beta-A (A-SCS, also called SUCLA2), which is known to catalyze the reversible conversion of succinyl-CoA and ADP to succinate and ATP in the TCA cycle as an essential factor that promotes the survival of disseminated cancer cells during metastasis. We demonstrate that A-SCS manages redox balance during tumor metastasis, and this metabolic contribution is independent of its role in the TCA cycle. Mechanistically, A-SCS relocates from the mitochondria to the cytosol and binds to stress granules, promoting stress granules to express the redox-scavenging enzyme catalase upon cell detachment. This mitigates oxidative stress and makes cancer cells survive through anoikis, eventually promoting metastasis. A clinical correlation study comparing primary and metastasized tumors collected from lung cancer patients demonstrated that A-SCS levels align with catalase expression as well as the metastatic progression of lung cancer. Our finding provides an academic basis for developing new treatment targets against metastasis, which strikes elevated mitochondrial metabolism during cancer cell dissemination.
Citation Format: Jihoon Kang, Jung Seok Hwang, Austin C. Boese, Sydney Shuff, Jaehyun Kim, Kiyoung Eun, Sumin Kang. Succinyl-CoA synthetase Beta-A: A novel metastasis promoting factor in lung 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 1551.
Abstract 1556: AMIGO2 is associated with the peritoneal dissemination in serous ovarian cancer by enhancing its adhesion to peritoneal mesothelial cells
Authors: Iida Yuki , Sato Shinya , Yamamoto Koji , Hikino Kohei , Okawa Masayo , Hosokawa Masayo , Sawada Mayumi , Komatsu Hiroaki , Kudoh Akiko , Seong Hee Kyung , Izutsu Runa , Osaki Mitsuhiko , Okada Futoshi , Taniguchi Fuminori 
Published: March 2024

Abstract
Amphoterin-induced gene and open reading frame 2 (AMIGO2) has been associated with the prognosis of colorectal, gastric, and cervical cancer. However, its relationship with ovarian cancer remains unclear. This study aimed to clarify the role of AMIGO2 in ovarian cancer. The research involved evaluating AMIGO2 expression in patients with ovarian serous carcinoma using immunohistochemistry. The AMIGO2-high group exhibited significantly shorter progression-free survival (PFS) compared to the AMIGO2-low group. The predictive index of the AMIGO2-high group was considerably higher than that of the AMIGO2-low group. The rate of complete cytoreductive surgery was lower in the AMIGO2-high group than in the AMIGO2-low group. Furthermore, in vitro studies showed that four serous ovarian cancer cell lines expressed AMIGO2 expression and adhesion to mesothelial cells. Adhesion to mesothelial cells was attenuated by AMIGO2 knockdown in SKOV3 cells. Moreover, in a murine model, AMIGO2 downregulation in SKOV3 cells significantly suppressed peritoneal dissemination. These findings suggest that high AMIGO2 expression in serous ovarian carcinoma cells contributes to a poor prognosis by promoting peritoneal metastasis through enhanced cell adhesion to mesothelial cells.
Citation Format: Yuki Iida, Shinya Sato, Koji Yamamoto, Kohei Hikino, Masayo Okawa, Masayo Hosokawa, Mayumi Sawada, Hiroaki Komatsu, Akiko Kudoh, Hee Kyung Seong, Runa Izutsu, Mitsuhiko Osaki, Futoshi Okada, Fuminori Taniguchi. AMIGO2 is associated with the peritoneal dissemination in serous ovarian cancer by enhancing its adhesion to peritoneal mesothelial 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 1556.
Abstract 16: CD4+ and CD8+ TCRαβ-deficient bioluminescent reporter T cells for screening and characterization of neoantigen-specific TCRs
Authors: Cong Mei , Grailer Jamison , Slater Michael , Stecha Pete , Hartnett Jim 
Published: March 2024

Abstract
Adoptive antigen-specific T cell therapy is currently comprised of chimeric antigen receptor (CAR) and T cell receptor (TCR) engineered T cells. Clinical results from CAR-T cells have demonstrated promising results in treating leukemias, while TCR-engineered T cells, which have the advantage of recognizing intracellular tumor antigens, is still in early development. Here, we report the development of CD4+ or CD8+ TCRαβ-KO reporter T cell lines for the screening and characterization of transgenic TCRs. A TCRαβ-KO reporter T cell line was first developed by knocking out the endogenous TCR α and β chains in the reporter T cell line using CRISPR/Cas9. Successful knockout was confirmed by phenotypic assays and TCR v chain locus sequencing. We demonstrated that re-introduction of influenza hemagglutinin (HA) peptide-specific TCR (HA1.7) α and β chains into TCRαβ-KO reporter T cell lines results in HA peptide-dependent TCR activation and luciferase reporter expression when HA peptide is presented by a MHCII+ cell line. Similarly, re-introduction of MART-1-specific TCR (DMF5) resulted in MART-1-dependent activation in the presence of MHCI+ cells. The select expression of CD4- or CD8-expressing variants of the TCRαβ-KO reporter T cell line enables the development of transgenic TCRs for both MHCI- and MHCII-restricted tumor antigen targets. Further development of CD4/CD8 double-positive and double-negative cell lines enables screening of low and high affinity TCRs without MHC bias. Together, this TCRαβ-KO platform represents a powerful tool for the screening and characterization of neoantigen-specific TCRs.
Citation Format: Mei Cong, Jamison Grailer, Michael Slater, Pete Stecha, Jim Hartnett. CD4+ and CD8+ TCRαβ-deficient bioluminescent reporter T cells for screening and characterization of neoantigen-specific TCRs [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 16.
Abstract 161: Aged mice decelerate bone metastasis of prostate cancer by decreasing infiltration of M2 macrophages
Authors: Zhang Xiao , Yu Wei , Huang Xin , Lu Yi , Zhang Jian 
Published: March 2024

Abstract
Bone metastasis is a major contributor to the mortality of patients with prostate cancer and results in the development of an immunosuppressive microenvironment in the bone marrow. While advanced age increases the risk of bone metastasis, effects of age-related changes on immune microenvironmental homeostasis are not yet clearly understood. To investigate interactions between cancer cells and the immune microenvironment in elderly individuals, we utilized murine-derived specific bone metastatic prostate cancer cells (RM1-BM), which we had previously isolated from bone metastatic mice and transfected with a luciferase-based reporter gene. We then injected the cells into the left ventricle of both 3‒6 months and 22‒24 months, male, wild-type mice to induce bone metastasis, using age-matched mice injected with PBS as a control. We employed in vivo imaging to compare the metastatic levels in both groups of mice every other day. On day 14, we extracted bone marrow cells for CyTOF analysis and femurs and tibias for Hematoxylin and Eosin staining. Interestingly, our preliminary results demonstrated that healthy aged mice exhibited a lower susceptibility to develop bone metastasis when compared to their younger counterparts. A further investigation of the immune subtypes revealed an increase in the percentage of macrophages in CD45+ immune cells in young mice that developed bone metastasis as opposed to age-matched controls. However, the percentage decreased in aged mice, going from 12.20% to 9.92% (p = 0.001). Lastly, macrophages were isolated from the bone marrow of 3‒6 months and 22‒24 months old mice and were co-cultured with ovalbumin-transfected RM1-BM cells (RM1-BM-ova) in vitro for 24 hours. The flow cytometry results indicated that both groups consist mainly of CD206+ (M2) macrophages. Nonetheless, those obtained from aged mice exhibited reduced ovalbumin presentation capability while maintaining a steady level of type I major histocompatibility complex (MHC-I). These findings suggested that increased infiltration of pro-inflammatory M2 macrophages within the tumor microenvironment may contribute to the bone metastasis of prostate cancer. Therefore, inhibiting M2 macrophages recruitment to the bone marrow microenvironment may prove a useful approach for treating patients with prostate cancer bone metastasis. This study was supported by the NSFC projects (81972420, 81972766, 82173336), and grants from the Shenzhen Science and Technology Innovation Commission (JCYJ20190809161811237, JCYJ20210324104214040).
Citation Format: Xiao Zhang, Wei Yu, Xin Huang, Yi Lu, Jian Zhang. Aged mice decelerate bone metastasis of prostate cancer by decreasing infiltration of M2 macrophages [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 161.
Abstract 1680: Roles of EphA2 receptor signaling in prostate cancer development and progression
Authors: Lingerak Ryan , Petty Aaron , Guo Hong , Lin Hebei , Shi Xiaojun , Kim Soyeon , Wang Bingcheng 
Published: March 2024

Abstract
Aggressive forms of prostate cancer (PCa), while initially responsive to androgen deprivation therapy (ADT), inevitably become resistant to therapy and are considered castration resistant PCa (CRPC). A major goal of PCa research has been to broadly identify molecular and cellular mechanisms that aid this progression to identify potential therapeutic targets. Using a combination of human data and unique animal models, we found that the receptor tyrosine kinase (RTK) EphA2 is overexpressed specifically in castration resistant and advancing prostate cancers. Furthermore we show that in metastatic PCa the receptor undergoes ligand-independent oncogenic signaling mediated by phosphorylation of EphA2 at S897. Together our data indicate a potential mechanism in PCa progression in which EphA2 becomes overexpressed and aids acquisition of castration resistance via acting as a driver of cell migration, invasion, and proliferation.
Citation Format: Ryan Lingerak, Aaron Petty, Hong Guo, Hebei Lin, Xiaojun Shi, Soyeon Kim, Bingcheng Wang. Roles of EphA2 receptor signaling in prostate cancer development and progression [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 1680.
Abstract 1707: YAP-driven epigenetic reprogramming in head and neck cancer
Authors: Officer Adam , Faraji Farhoud , Ramirez Sydney , Goren Alon , Tamayo Pablo , Gutkind J. Silvio 
Published: March 2024

Abstract
The ability to measure tumor evolution is difficult due to a lack of model systems able to capture tumor initiation, development, and invasion. We have developed a Dox-inducible spatiotemporally controlled HPV- and YAP-driven model of head and neck squamous cell carcinoma (HNSCC) with a well-defined cancer stem cell population. In order to better understand the epigenetic reprogramming associated with tumorigenesis we have systematically characterized the chromatin accessibility, histone landscape and YAP binding sites in this model.
Cell lines were generated from tongue epithelia of normal and Dox-induced tumor-containing mice. Gene expression was measured using RNA-seq and chromatin accessibility was measured using ATAC-seq. CUT&Tag for H3K27me3, H3K27ac, and YAP was used to measure epigenetic reprogramming and YAP-DNA interactions.
Differential gene expression shows that genes involved in hormone signaling, glutathione-related metabolism, fatty acid metabolism and p53 signaling were highly enriched in the normal tongue suggesting a change in metabolism upon tumorigenesis.Differential ATAC-seq peaks with higher binding levels in the normal tongue showed enrichment for p53 motifs as well as homebox motifs including Otx2, GSC and CRX suggesting p53 signaling is lost upon carcinogenesis and lineage determination is altered. Motifs for TEAD, AP-1, and KLF5 were enriched in the tumor-specific ATAC-seq peaks showing that YAP is involved in chromatin accessibility changes. CUT&Tag for YAP shows clear YAP binding near canonical YAP target genes including Axl, Ccn1, Ccn2 and Birc3. YAP peaks with higher binding in the normal tongue cell line were enriched for RUNX2 and p63 motifs and peaks higher in the tumor contained KLF5 motifs showing YAP is directly involved in the reprogramming of lineage determination. Multi-omics integration shows YAP-driven chromatin remodeling is associated with differential expression of genes involved in keratin production, EGFR and ER signaling.
Direct epigenetic characterization of YAP involvement in tumor initiation is key to understanding the mechanisms of tumorigenesis in head and neck cancer. This work shows that YAP directly binds and affects the expression of genes involved in lineage determination and growth factor signaling to induce cancer progression and generate a cancer stem cell population.
Citation Format: Adam Officer, Farhoud Faraji, Sydney Ramirez, Alon Goren, Pablo Tamayo, J. Silvio Gutkind. YAP-driven epigenetic reprogramming in head and neck 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 1707.
Abstract 1747: The mutational landscape and its longitudinal dynamics in relapsed and refractory Hodgkin lymphoma
Authors: Witte Hanno , Künstner Axel , Hahn Thomas , Bernard Veronica , Stoelting Stephanie , Kusch Kathrin , Nagarathinam Kumar , von Bubnoff Nikolas , Khandanpour Cyrus , Bauer Arthur , Grunert Michael , Arndt Annette , Steinestel Konrad , Merz Hartmut , Busch Hauke , Feller Alfred , Gebauer Niklas 
Published: March 2024

Abstract
Introduction: In classical Hodgkin-lymphoma (cHL), only a few cases recur, and only a limited fraction of patients is primary-refractory to standard-polychemotherapy. Underlying genomic features of unfavorable clinical courses remain sparsely characterized. Here, we investigated the genomic characteristics of primary-refractory/relapsed cHL in contrast with long-term-responders (LTR).
Methods: Therefore, ultra-deep next-generation panel-sequencing was performed on a total of 59 samples (20 LTR, 26 relapsed (rHL: 11 initial-diagnosis, 15 relapse) and 13 primary-refractory (prHL: 8 initial-diagnosis, 5 progression) from 44 cHL-patients applying a hybrid-capture approach. We compared samples associated with distinct disease courses concerning their oncogenic drivers, mutational signatures, and perturbed pathways.
Results: Compared to LTRs, mutations in genes such as PMS2, PDGFRB, KAT6A, EPHB1, and HGF were detected more frequently in prHL/rHL. Additionally, we observed that in rHL or prHL, BARD1-mutations occur, whereas ETV1, NF1, and MET-mutations were eliminated through clonal selection. A significant enrichment of non-synonymous variants was detected in prHL compared to LTRs and a significant selection process in favor of NOTCH-pathway mutations driving rHL or prHL was observed.
Conclusion: This study delineates distinct mutational signatures between LTR and rHL/prHL, whilst illustrating longitudinal dynamics in mutational profiles using paired samples. Further, several exploitable therapeutic vulnerabilities for rHL and prHL were identified.
Citation Format: Hanno Witte, Axel Künstner, Thomas Hahn, Veronica Bernard, Stephanie Stoelting, Kathrin Kusch, Kumar Nagarathinam, Nikolas von Bubnoff, Cyrus Khandanpour, Arthur Bauer, Michael Grunert, Annette Arndt, Konrad Steinestel, Hartmut Merz, Hauke Busch, Alfred Feller, Niklas Gebauer. The mutational landscape and its longitudinal dynamics in relapsed and refractory Hodgkin lymphoma [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 1747.