bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 6759: Antigen-pHLIP for tumor treatment
Authors: DuPont Michael , Visca Hannah , Moshnikova Anna , Engelman Donald , Reshetnyak Yana , Andreev Oleg 
Published: March 2024

Abstract
Targeted antigen delivery allows activation of the immune system to kill tumor cells. Among the immunogenic epitopes widely investigated is α-Gal, since humans exhibit specific anti-Gal reactivity. However, the repertoire of immunogenic epitopes could be significantly enhanced if therapeutic efficacy did not rely on the presence of natural antibodies, but instead relied on the production of anti-epitope endogenous antibodies induced by immunization against the selected epitope. Therefore, we designed and tested several HA-pHLIP agents, where the HA peptide (YPYDVPDYA) from the influenza virus was selected as an exogenous highly immunogenic epitope, since it is absent in the human genome, and a pH Low Insertion Peptide (pHLIP) was selected as the tumor targeting agent. HA peptides were attached to the N-termini of pHLIPs either directly or via PEG polymers. To enhance the overall binding affinity of HA-pHLIP to anti-HA antibodies, double headed HA-pHLIP agents were introduced, where two HA epitopes were linked to a single pHLIP peptide via PEG12 polymers. The pHLIP sequence was modified to ensure proper pKs of insertion into cell membranes. HA epitopes were targeted to cancer cells in mouse tumors, and remained exposed to the extracelullar space within tumors for about 24 hours. Double-headed HA-pHLIP treatments of imunized mice (a high titer of anti-HA antibodies was developed in mice after immunization with KLH-HA), bearing 4T1 triple negative or B16F10 MHC-I negative melanoma tumors resulted in a 55% reduction of tumor growth. Further reduction of tumor growth was impossible to achive, since all of the anti-HA antibodies in the blood were captured after 3 injections of HA-pHLIP and additional boosts would be required to restore the level of free anti-HA antibodies to induce a more significant therapeutic efficacy.
Citation Format: Michael DuPont, Hannah Visca, Anna Moshnikova, Donald Engelman, Yana Reshetnyak, Oleg Andreev. Antigen-pHLIP for tumor treatment [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 6759.
Abstract 6801: Cellular senescence involves spatial evolution in colorectal cancer
Authors: Park Tae Jun , Kang Seok Yun , Kim Jang Hee , Lee Hyun Woo , Choi Yong Won , Park Soon Sang , Lee Young-Kyoung 
Published: March 2024

Abstract
Cancer evolution is a continuous process involving cellular changes that promote progression and metastasis. Recent studies demonstrate that cancer evolution is spatially associated: a phenomenon called “the spatial evolution of cancer.” In our data, colorectal cancer cells gradually evolve from an adenoid to a collective invasion morphology, ultimately developing a partial epithelial-mesenchymal transition phenotype as they form an invasive front. Trajectory analysis showed that cancer cells at the invasive front of a tumor exhibit a totally different gene expression pattern from those at the center, and that cellular senescence plays a crucial role in this transition. Epigenetic changes in the promoter/exon1 region of the CDKN2A gene caused by increased reactive oxygen species level are crucial for expression of p16INK4A and induction of senescence in the cancer cells. Two types of senescent tumor cells (type I and type II) were observed, and they played different roles in cancer progression due to different gene expression. Type II senescent tumor cells (p16INK4A+/LAMC2+/MMP7+), a final evolved form of cancer cells, are strongly associated with local invasion and lymph node metastasis of colorectal cancer and worsen the prognosis for patients.
Citation Format: Tae Jun Park, Seok Yun Kang, Jang Hee Kim, Hyun Woo Lee, Yong Won Choi, Soon Sang Park, Young-Kyoung Lee. Cellular senescence involves spatial evolution in colorectal 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 6801.
Abstract 6803: TRIM16 regulates IL-6 secretion in head and neck cancer-associated fibroblasts
Authors: Ly Thuc , Pickard Bailey , Pandey Avisha , Martinez-Rivera Noraida , Rosa-Molinar Eduardo , Washburn Michael , Ding Wen-Xing , Thomas Sufi Mary 
Published: March 2024

Abstract
Despite current therapy, head and neck squamous cell carcinoma (HNSCC), the 7th most common cancer worldwide, is associated with high morbidity and mortality. Response to current therapies could be improved with a better understanding of the tumor microenvironment of HNSCC. We previously reported that cancer-associated fibroblasts (CAFs), the most abundant stromal cell type in the HNSCC microenvironment, have elevated levels of basal autophagy than oral fibroblasts from cancer-free subjects (NF). Disrupting autophagy in CAFs with Beclin-1 siRNA reduced secretion of IL-6, IL-8, and other factors known to promote HNSCC progression. The recent emerging role of autophagy in secretion of tumor promoting factors has high impact because (i) the mechanism can provide a new target to block the secretion of protumor factors from CAFs that contribute to HNSCC progression, and (ii) these cytokines can serve as potential indicators for the efficacy of autophagy-targeted therapies. To this end, we carried out an unbiased assessment of the proteins associated with autophagosomes in primary CAFs from HNSCC samples using mass spectrometry. We performed immunoprecipitation of LC3B from the isolated small vesicles of the CAFs, identified and validated the association of several trafficking proteins in secretory autophagy including VAMP3 and SNAP23. Further, the tripartite motif (TRIM) proteins have been shown to mediate the fate of autophagosomes either for degradation or secretion. We hypothesized that TRIM proteins are involved in transport of secretory autophagosomes. Our data demonstrate CAFs express higher levels of TRIM16 mRNA than NF. We demonstrate immunogold labeling of TRIM16 or IL-6 localized to the autophagosomes using transmission electron microscopy. Further, using immunofluorescence, we demonstrated the colocalization of TRIM16 and IL-6, as well as IL-6 and LC3B in cytoplasmic puncta. In addition, we used proximity ligation assays to confirm the interaction of TRIM16 and IL-6, as well as IL-6 and LC3B. TRIM16 knockdown using siRNA in CAFs reduced the secretion of IL-6 as measured by ELISA. In conclusion, we demonstrate an important role of TRIM16 in secretory autophagy making it a potential therapeutic target to mitigate CAF-mediated HNSCC growth.
Citation Format: Thuc Ly, Bailey Pickard, Avisha Pandey, Noraida Martinez-Rivera, Eduardo Rosa-Molinar, Michael Washburn, Wen-Xing Ding, Sufi Mary Thomas. TRIM16 regulates IL-6 secretion in head and neck cancer-associated fibroblasts [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 6803.
Abstract 6808: Investigating the role of CXCR3+ monocytes on CAR T cell function
Authors: Ong Claire Victoria , Kaczanowska Sabina , Ju Wei , Cronk James , Ramakrishna Sneha , Kaplan Rosandra 
Published: March 2024

Abstract
Chimeric antigen receptor T cells (CAR-Ts) are an emerging immunotherapy that have remarkable efficacy against leukemias and lymphomas but limited success against solid tumors. We conducted a phase I clinical trial (NCT 02107963) of GD2 CAR-T (GD2-CAR.OX40.28.z.ICD9) administration to children and young adults with neuroblastoma and, for the first time, osteosarcoma. While all patients progressed and were switched to alternative therapy, we observed a significant association between good CAR-T expanders and expression of C-X-C Motif Chemokine receptor 3 (CXCR3) on monocytes detected in pretreatment apheresis. This study seeks to uncover the possible interactions between CXCR3 and CAR-Ts that may alter CAR-T function and ultimately lead to better CAR-T expansion. We hypothesize that CXCR3+ monocytes induce functional change in CAR-Ts resulting in improved expansion.
To recapitulate the interaction between tumor, CAR-Ts and monocytes, we took 143Bs (osteosarcoma cell line) and GD2 CAR-Ts and co cultured them with THP-1s (a monocytic leukemia cell line) that were either untransduced (UTD) or transduced via lentivirus to express CXCR3 (CXCR3+). The ratio of UTD or CXCR3+ THP-1s to CAR-Ts and 143Bs was varied between co cultures. Enzyme-linked immunoassay (ELISA) for interferon gamma (IFNy) expression was run as a proxy measurement for CAR-T cell activity. Flow cytometry was used to assess for expression of activation and exhaustion markers. Differences between UTD and CXCR3+ co cultures were evaluated for statistical significance via unpaired t-test.
We observed that CXCR3 was elevated on GD2 CAR-Ts co cultured with CXCR3+ monocytes. This pattern was seen most prominently in CD4+ CAR-Ts, but also subtly in CD8+ T-cells. Exhaustion markers CD39 and LAG3 were elevated in CAR-Ts co cultured with CXCR3+ monocytes. Additionally, CAR-Ts co cultured with CXCR3+ monocytes displayed greater activity via elevated IFNy expression.
We conclude that GD-2 CAR-T cells co cultured with CXCR3+ monocytes express elevated exhaustion markers due to possible increased activity when in the presence of CXCR3+ monocytes. Additionally, we suspect that elevated CXCR3 expression on CAR-Ts co cultured with CXCR3+ monocytes may be helping CAR-Ts better target tumor cells, thus leading to improved expansion. If CXCR3 can improve CAR-T cell function, this could lead to better optimization of CAR-Ts against solid tumors and create a viable treatment option for neuroblastoma and osteosarcoma patients.
Citation Format: Claire Victoria Ong, Sabina Kaczanowska, Wei Ju, James Cronk, Sneha Ramakrishna, Rosandra Kaplan. Investigating the role of CXCR3+ monocytes on CAR T cell function [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 6808.
Abstract 6844: Discovery of a novel sialic acid O-acetyltransferase in colon tissue
Authors: Lee Bum Seok , Cook Ashley , Zeineldin Maged , Sur Surojit , Dobbyn Laura , Popoli Maria , Khalili Sana , Vogelstein Bert , Papadopoulos Nickolas , Zhou Shibin , Bettegowda Chetan , Buckhaults Phillip , Larman Tatianna , Gabrielson Kathy , Kinzler Kenneth W. , Wyhs Nicolas 
Published: March 2024

Abstract
Sialic acids have critical functions relating to host-pathogenic interactions and the immune microenvironment. Subsequent post-translational O-acetyl modifications add an extra layer of control by modulating many of these interactions in both normal and transformed colorectal cells. The processes through which this modification is added to sialic acids are not completely understood. To date only one gene, CASD1, has been identified to encode a sialic acid O-acetyltransferase in human cells. We used whole-genome sequencing on normal human colon tissue to identify a haplotype strongly associated with colorectal sialic acid O-acetylation, as determined by histopathological mPAS staining. Only SNP’s of a single candidate gene within the haplotype correlated perfectly in a 91-sample validation set. CRISPR-Cas9 editing of this gene in 2D cell line and 3D normal colon organoid models yielded changes to modified sialic acid levels. These findings suggest that this candidate gene functions as a novel sialic acid O-acetyltransferase in colorectal tissue and could have implications as a diagnostic tool for patients with inflammatory diseases of the bowel or as an indicator for therapeutic targets in cancer.
Citation Format: Bum Seok Lee, Ashley Cook, Maged Zeineldin, Surojit Sur, Laura Dobbyn, Maria Popoli, Sana Khalili, Bert Vogelstein, Nickolas Papadopoulos, Shibin Zhou, Chetan Bettegowda, Phillip Buckhaults, Tatianna Larman, Kathy Gabrielson, Kenneth W. Kinzler, Nicolas Wyhs. Discovery of a novel sialic acid O-acetyltransferase in colon tissue [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 6844.
Abstract 6845: MAGEA3 expression and secretion in MMR-MSH6 and MMR-PMS2 microsatellite-stable colorectal cancer
Authors: Yom Jina , Gonzalez Rachel , Gilmore Bailey , Guo Zhaoying , Han Andy , Zewdu Eden , Kong Dehe , Qu Tianli , Guo Hailey , Strom Alex , Zhao Zoe , Hu Xiaomin , Ren Qi , Ma Yan , Zhang Ranran , Wu Zhaohui , Liu Xuan , Fu Wei 
Published: March 2024

Abstract
Despite the breakthrough of PD-1/PD-L1 blockade therapy in the recent years, mixed responses have been shown across multiple tumor types, including in colorectal cancer (CRC), the second leading cause of death worldwide. This immunotherapy has proven to be successful for a subtype of CRC that carries mismatch repair deficiency (dMMR) and high microsatellite instability (MSI-H), despite a lack of response by microsatellite-stable CRC. For these types of non-responsive cancers, new immunotherapy targets are currently being investigated for alternative therapy such as the MAGE-A cancer testis antigen family whose expression is restricted to germline cells in normal tissue but is overexpressed in many cancer cells. In this study, we examine the relationship between MAGEA3 and MMR proteins MSH6 and PMS2. Immunohistochemical staining of CRC tissues demonstrated co-expression between MAGEA3 with both MSH6 and PMS2. Immune cells were observed to express MAGEA3 in CRC as well. To investigate the possibility of secreted MAGEA3 from tumor cells, we performed western blot analysis of CRC cell lines, ELISA, and binding assay on cell lines and the positive results suggest that MAGEA3 protein is secreted. The results suggest that MAGE-A3 may be a promising target for microsatellite-stable colorectal cancer immunotherapy.
Citation Format: Jina Yom, Rachel Gonzalez, Bailey Gilmore, Zhaoying Guo, Andy Han, Eden Zewdu, Dehe Kong, Tianli Qu, Hailey Guo, Alex Strom, Zoe Zhao, Xiaomin Hu, Qi Ren, Yan Ma, Ranran Zhang, Zhaohui Wu, Xuan Liu, Wei Fu. MAGEA3 expression and secretion in MMR-MSH6 and MMR-PMS2 microsatellite-stable colorectal 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 6845.
Abstract 6847: IGF2BP3 promotes esophageal squamous cell carcinoma progressions via Wnt/CTNNB1 pathway
Authors: Tian Zhongxian , Zhou Yongjia , Ding Yi , Wu Zhengwen , Zhao Xiaogang 
Published: March 2024

Abstract
The M6A RNA modification plays a crucial role in the progression of tumors. Simultaneously, IGF2BP3 is primarily expressed in the tumor cells of squamous cell carcinoma, rather than in stromal cells, including esophageal squamous cell carcinoma (ESCC), a subtype mainly prevalent in East Asia. However, the mechanism of IGF2BP3 in the progression of esophageal squamous cell carcinoma and its role in the tumor microenvironment (TME) remain unknown and require further exploration. Our research reveals that IGF2BP3 not only plays a significant oncogenic role in tumor cells, including the activation of the Wnt pathway, PI3K-AKT pathway, and MAPK pathway, but also, the high expression of IGF2BP3 is positively correlated with the enrichment of M2 macrophages in ESCC tissues, in the TME, IGF2BP3 promotes the infiltration of M2 macrophages, ultimately facilitating the progression of ESCC. Mechanistically, IGF2BP3 enhances the translation of USP36 mRNA by directly binding to its mRNA, rather than increasing the stability of mRNA. The IGF2BP3-mediated USP36 protein elevation enhances the binding capacity with CTNNB1 protein, reducing its degradation through the ubiquitin-proteasome pathway, and following improved the Wnt/CTNNB1 pathway activating, Ultimate, IGF2BP3 aggravated the malignancy of the tumor. Additionally, the activation of the Wnt pathway promotes TGFB1 transcription and secretion, subsequently activating the polarization of M2 macrophages, infuriating the formation of the tumor immune-suppressive microenvironment, ultimately promoting the progression of esophageal squamous cell carcinoma. Our findings strongly emphasize the oncogenic role of IGF2BP3 in the progression of ESCC both in vitro and in vivo, providing new insights and perspectives for the treatment of esophageal squamous cell carcinoma.
Citation Format: Zhongxian Tian, Yongjia Zhou, Yi Ding, Zhengwen Wu, Xiaogang Zhao. IGF2BP3 promotes esophageal squamous cell carcinoma progressions via Wnt/CTNNB1 pathway [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 6847.
Abstract 6858: PPARδ and type 1 interferon collaboratively regulate CIITA-MHCII pathway: Unveiling novel mechanisms of tumor Tregs
Authors: Yang Qiyuan , Liang Yuqiong , Zheng Ye 
Published: March 2024

Abstract
Regulatory T cells (Tregs) play an essential role in suppressing anti-tumor immunity, often resulting in unfavorable clinical outcomes across numerous cancers. However, systemic Treg depletion, while augmenting anti-tumor responses, also triggers detrimental autoimmune disorders. Thus, dissecting the mechanisms by which Tregs navigate and exert their functions within the tumor microenvironment (TME) is pivotal for devising innovative Treg-centric cancer therapies. Our study highlights the role of peroxisome proliferator-activated receptor β/δ (PPARδ), a nuclear hormone receptor involved in fatty acid metabolism. Remarkably, PPARδ ablation in Tregs escalated tumor growth and augmented the immunosuppressive characteristics of the TME. This absence of PPARδ spurred an increased expression of genes central to antigen presentation, notably CIITA and MHCII. Our results showcase a novel association where the absence of CIITA in PPARδ-deficient Tregs bolsters anti-tumor responses, casting CIITA as a pivotal downstream regulator of PPARδ within Tregs. In vitro assays demonstrated that elevated CIITA levels enhance the suppressive capacity of Tregs, facilitated by an antigen-independent interaction between Treg-MHCII and Tconv-TCR/CD4/Lag3. A significant revelation was the role of type 1 interferon as a TME signal that promotes the genesis of MHCII+ Tregs; this process is accentuated by PPARδ deficiency. In conclusion, the co-regulation between TME cues and PPARδ signaling shapes the adaptive and suppressive roles of Treg cells through the CIITA-MHCII pathway. Strategically targeting the potent MHCII+ Treg population could open a new avenue for cancer therapies by boosting anti-tumor defenses while curbing autoimmune threats.
Citation Format: Qiyuan Yang, Yuqiong Liang, Ye Zheng. PPARδ and type 1 interferon collaboratively regulate CIITA-MHCII pathway: Unveiling novel mechanisms of tumor Tregs [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 6858.
Abstract 6916: InnoPanelTMand InnoPediaTM: resources of engineered cell lines and xenografts for drug discovery
Authors: Li Siyu , Liu Chang , Wang Na , Hu Yuqing , Ning Jinying , Hao Feng 
Published: March 2024

Abstract
The Development of precision medicine relies on well-characterized experimental models that carry naive, induced, or engineered genomic and epigenetic features targetable by certain treatments. Patient-derived xenografts (PDX) and cell lines can serve as such in vivo and in vitro models by harboring abnormalities such as somatic and driver mutations, dysregulated gene expression and silencing, microsatellite instability, gene fusions, copy number amplification and loss of heterozygosity. In addition, cell lines can also be engineered to introduce sometimes rare-occurring abnormalities that the engineered cell line shares an identical genetic background with its parental cell line, thus providing a clearly contrasting pair to evaluate treatment specificity. With the advancement of disease research and drug discovery, existing cell lines can no longer meet the needs of various types of drug discovery. To evaluate drug efficacy more quickly and accurately, Kyinno has constructed and identified more than 4,000 engineered cell lines, including overexpressed cell lines constructed through transposon systems or lentivirus infection, gene-edited cell lines constructed through CRISPR-Cas9 technology, and reporter cell lines targeting multiple signaling pathways and membrane receptors. Besides, InnoPanelTM, a panel of over 1000 engineered cell lines was established and characterized to cover a wide range of heavily targeted genes such as CLDN18.1, CLDN18.2, LAG3, OX40, PD-L1, PD-L2, and TIM3. Cell line families were also developed for genes with multiple known driver mutations. All cell lines are annotated with background information, engineering details, functional characterization, and efficacy studies. Furthermore, we developed xenografts for several engineered cell lines and showed that the combination of cell lines and xenografts can accelerate drug development. Additionally, all of this information can be accessed in our free database, InnoPediaTM. The database also offers browsing, searching, and analytical capabilities for over 600 commonly used tumor cell lines and thousands of engineered cell lines with essential genomic and pharmacological data, cell line efficacy data for nearly 2000 common anti-tumor drugs, and comprehensive details for over 100 standard antibodies. Our engineered cell lines are now registered in the online cell line database Cellosaurus, which is available on the ExPASy server.
Citation Format: Siyu Li, Chang Liu, Na Wang, Yuqing Hu, Jinying Ning, Feng Hao. InnoPanelTMand InnoPediaTM: resources of engineered cell lines and xenografts for drug discovery [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 6916.