bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 6351: Reversal of dysfunctional CIK cells after the exposure to resistant cholangiocarcinoma cells through chemical perturbation of resistant gene signature
Authors: Wongkajornsilp Adisak , Htwe Khin Su Su , Chusorn Porncheera , Duangsa-ard Sunisa , Kasetsinsombat Kanda , Sawatpiboon Nathawadee 
Published: June 2023

Abstract
Clinical trials on cholangiocarcinoma revealed differential sensitivity to cytolytic action of allogeneic cytokine-induced killer (CIK) cells. Different metastatic foci in the same individual could also display different sensitivity. The differential sensitivity of separate lines of cultured cholangiocarcinoma cells could be demonstrated based on the evaluation of GR50. Allogeneic CIK cell or CD3+CD56+ subset was co-cultured with nine cell lines at E:T ratio of 20:1 for 48 h. The tumor cells were categorized into 2 groups based on the obtained GR50. This resulted in 4 sensitive cell lines and 5 resistant cell lines. The cholangiocarcinoma cell-exposed CIK cell and CD3+CD56+ subset displayed defective anti-tumor cytotoxicity upon subsequent experiment. RNAseq analysis revealed 261 genes upregulated in sensitive cell lines and 665 genes upregulated in resistant cell lines. The top 50 resistant genes were evaluated for their linked signal transduction and protein interaction network. Based on the interaction network, a list of chemicals that could interrupt the stipulated network were selected. They were assayed for their synergistic activity with dysfunctional CIK cell or CD3+CD56+ subset for cytolysis of resistant tumor cells.
Citation Format: Adisak Wongkajornsilp, Khin Su Su Htwe, Porncheera Chusorn, Sunisa Duangsa-ard, Kanda Kasetsinsombat, Nathawadee Sawatpiboon. Reversal of dysfunctional CIK cells after the exposure to resistant cholangiocarcinoma cells through chemical perturbation of resistant gene signature [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6351.
Abstract 6359: Structural insights into Siglec-15 reveal glycosylation dependency for interaction with T cells through integrin CD11b
Authors: Lenza Maria Pia , Egia-Mendikute Leire , Antoñana-Vildosola Asier , Soares Cátia O. , Corzana Francisco , Oyenarte Iker , Marcelo Filipa , Jiménez-Barbero Jesús , Ereño-Orbea June , Palazon Asis 
Published: June 2023

Abstract
Sialic acid-binding Ig-like lectin 15 (Siglec-15) is emerging as an immune modulator and target for cancer immunotherapy. However, limited knowledge regarding the mechanism of action, structure and binding partners on T cells restrains the development of drug candidates that unleash its full therapeutic potential. Here, we solve the crystal structure of Siglec-15 and delineate its binding epitope by co-crystallization with an anti-Siglec-15 blocking antibody. Saturation transfer-difference (STD) nuclear magnetic resonance (NMR) spectroscopy assisted with molecular dynamic simulations revealed the binding mode of Siglec-15 to the cancer-associated sialyl-Tn (sTn) glycoform. Binding of Siglec-15 to T cells, which lack sTn expression, depends on the presence of sialic acid. We identified the leukocyte integrin CD11b as a binding partner of Siglec-15 on human T cells. Collectively, these data provide an integrative understanding of the structural features of Siglec-15 and underscore glycosylation as an additional layer of control of T cell responses.
Citation Format: Maria Pia Lenza, Leire Egia-Mendikute, Asier Antoñana-Vildosola, Cátia O. Soares, Francisco Corzana, Iker Oyenarte, Filipa Marcelo, Jesús Jiménez-Barbero, June Ereño-Orbea, Asis Palazon. Structural insights into Siglec-15 reveal glycosylation dependency for interaction with T cells through integrin CD11b [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6359.
Abstract 6428: Targeting SMARCAL1 as a therapeutic strategy to enhance cGAS/STING signaling in gastric cancer
Authors: Hsu Po-Yen , Chuang Yu-Ming , LIN Shu-Hui , Lee Yu-Ting , Chen Yin-Chen , Ng Enders K.W. , YEH Kun-Tu , Cheng Alfred S.L. , Chan Michael W.Y. 
Published: June 2023

Abstract
Gastric cancer is one of the leading causes of cancer death in Eastern Asia. Although immunotherapy, such as immune checkpoint blockade, is an emerging therapeutic strategy against gastric cancer, only a fraction of cancer patients show a therapeutic response. Therefore, developing a novel therapeutic strategy to turn a “cold” tumor into a “hot” tumor is considered a crucial issue in cancer treatment. By methylomic analysis, we found that SMARCAL1 is one of the STAT3 targets which might be regulated by STAT3-mediated promoter methylation. Moreover, an inverse correlation between SMARCAL1 promoter methylation and expression was observed in the TCGA online database and in our cell lines experiment. Bisulfite pyrosequencing also showed a significant hypomethylation of SMARCAL1 compared to gastritis and adjacent normal in our in-house cohort (gastritis n=15; IM n=13; cancer n=58). More importantly, SMARCAL1 knockdown showed increased sensitivity of gastric cancer cell lines to DNA-damaging agents and increase the expression of cGAS and its downstream target, IFNB1. Therefore, in this study, we propose SMARCAL1 as a therapeutic target for improving the efficiency of immunotherapy by enhancing the cGAS/STING signaling pathway.
Citation Format: Po-Yen Hsu, Yu-Ming Chuang, Shu-Hui LIN, Yu-Ting Lee, Yin-Chen Chen, Enders K.W. Ng, Kun-Tu YEH, Alfred S.L. Cheng, Michael W.Y. Chan. Targeting SMARCAL1 as a therapeutic strategy to enhance cGAS/STING signaling in gastric cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6428.
Abstract 6435: BCG008, a human Siglec-15 blocking antibody, displays potent anti-tumor activity in Siglec-15-humanized mice
Authors: Yang Yongfei , Qu Aidong , Yao Fengping , Song Pan , Liang Hongyuan , Tian Maopeng , Yang Fang , Yu Zhaoxue , Zhou Xu , Li Xiuling 
Published: June 2023

Abstract
Sialic acid-binding Ig-like lectin 15, or Siglec-15, is identified as a critical immune suppressor. Siglec-15 expression is normally limited to certain myeloid cells, but it can be upregulated in a variety of tumors and on tumor-infiltrating myeloid cells. Siglec-15 significantly inhibits antigen-specific T cell responses both in vitro and in vivo. Conversely, genetic ablation of Siglec-15 promotes anti-tumor responses. Therefore, a Siglec-15-targeting blocking antibody could represent a novel class of anti-tumor immunotherapy. BCG008, a fully human monoclonal antibody antagonist of Siglec-15, was generated from RenMab™ mice, which contain the entire human immunoglobulin variable domain. Compared to a reference Siglec-15 blocking antibody (5G12), BCG008 exhibited higher affinity for human and cynomolgus monkey Siglec-15 and targeted distinct binding epitopes. In in vitro studies, BCG008 significantly abrogated Siglec-15-mediated T cell suppression in a dose-dependent manner, as measured by CD4+ and CD8+ T cell proliferation. Subsequently, the efficacy and safety of BCG008 was evaluated in syngeneic tumor models in Siglec15-humanized mice. BCG008 monotherapy significantly inhibited tumor growth, and the effect of the tumor inhibition was potentiated when administered in combination with other immune-checkpoint inhibitors, including anti-PD-L1 antibodies. In safety evaluation, BCG008 was well-tolerated in the tumor-bearing mice; no adverse effects were observed even at high doses (e.g. 30 mg/kg). Taken together, these results demonstrate that BCG008 is a novel anti-human Siglec-15 blocking antibody with favorable efficacy and safety profiles that can provide potential benefits for future cancer immunotherapy.
Citation Format: Yongfei Yang, Aidong Qu, Fengping Yao, Pan Song, Hongyuan Liang, Maopeng Tian, Fang Yang, Zhaoxue Yu, Xu Zhou, Xiuling Li. BCG008, a human Siglec-15 blocking antibody, displays potent anti-tumor activity in Siglec-15-humanized mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6435.
Abstract 6438: Next-generation pan-cancer immunotherapy with patient-derived APC
Authors: Bian Zhen , Shi Lei , Liu Yuan , Stylli harry 
Published: June 2023

Abstract
Harnessing phagocytic antigen presenting cells (APC) and tumor neoantigen-specific T cells represent the ultimate power of immunotherapy against cancer. The promises of phagocytic APCs lie in their abilities of not only initiating phagocytosis towards cancer cells (to “eat off” tumor) but also, through immunogenic antigen presentation, activating neoantigen-specific Tcells that systemically and durably eliminate cancer cells, as well as the establishment of a long-lasting cellular and hormonal immunity that prevents tumor recurrence. However, the efforts of developing APCs -based therapy have been hindered by the current lack of technology that robustly produce APCs from cancer patients, as none of the traditional methods for differentiating DC or macrophage APCs are effective for cancer patients.
Through a proprietary process, we have created a unique reagent combo that enables robust differentiation of cancer patients’ peripheral monocytes (cMo) to be potent APC, termed κAPC. κAPC display a unique gene expression profile, separating from classical DC or macrophage, and profound proinflammatory phenotype with enhanced phagocytic capability and elevated immunogenic antigen presentation machinery. In both in vitro and in vivo settings, κAPC demonstrate direct uptake of tumor antigens and presentation to T cells, the latter leading to activation and large expansion of multi-targeting, polyclonal tumor-specific CD4 and CD8 T populations - termed NeoT- from circulating and tumor-infiltrating lymphocytes. Theexpanded CD8 NeoT are highly tumoricidal and once adoptively transferred in vivo, potently eliminated late-stage metastatic solid tumors, whereas CD4 NeoT contribute to immune memory and repolarize a proinflammatory TME favorable for tumor elimination.
Key words: κAPC, NeoT, NeoT adoptive cell therapy, κAPC-based cancer vaccine, combination therapies
Citation Format: Zhen Bian, Lei Shi, Yuan Liu, harry Stylli. Next-generation pan-cancer immunotherapy with patient-derived APC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6438.
Abstract 644: Gut microbiota-derived metabolites as regulators of immunity in pre-cancer
Authors: Mohseni Amir Hossein , Taghinezhad-S Sedigheh , Beatty Pamela L. , Finn Olivera J. 
Published: June 2023

Abstract
Introduction: Tryptophan (Trp) as an essential amino acid that can only be obtained through diet and is a precursor of serotonin and melatonin and required for protein and niacin biosynthesis. In addition, Trp is appreciated for its influence on both host and microbial metabolism. Trp is shunted into the Kyn pathway (mostly) and indolic pathway (bacterial degradation), especially in the immune cells. Both Kyn and Indole/indole derivatives, in part by activating the ligand-dependent transcription factor aryl hydrocarbon receptor (AHR), can become dysfunctional in cancer. Most individuals with cancer such as colon cancer, exhibit increased L-kynurenine levels, which in part is explained by progression of immunosuppressive phenotype and excessive inflammatory signaling molecules. To date, studies in mice and humans have linked Kyn and AHR as potent modulators of host immunity to colon cancer (CRC). Nothing is yet known about their role in pre-cancer, during the development of adenomatous polyps. We hypothesized that increases in plasma Kyn and I3A and their receptor AHR on immune cells would be detected in patients with pre-malignant polyps, suggesting dysbiosis and increased colon cancer risk due to immune modulation.
Methods: We measured with mass spectrometry Kyn and I3A in plasma samples of 88 polyp patients and compared to 22 colon cancer patients. We analyzed by flow cytometry PBMCs from 64 newly diagnosed advanced polyp patients (40-70 years old) and 9 age-matched colon cancer patients in order to evaluate AHR expression in different subsets of T cells, NKT cells and NK cells, and their possible association with exhaustion markers Tim-3, LAG-3 and PD-1, as well as Granzyme K, and the presence of immunosuppressive Treg and MDSC.
Results: We showed high level of expression of gut microbiota-derived metabolites in plasma of colon pre-cancer compared to cancer patients. We identified CD8+ T effector memory cells (TEM) as primary T cell population expressing their receptor AHR in polyp patients, which had a statistically significant association with Granzyme K expression, which is a hallmark of inflammaging.
Conclusions: Our results suggest gut microbiota-derived metabolites as potential mediators of immunosuppression in the setting of premalignancy, which could increase cancer risk and be targets of cancer-preventing strategies.
Citation Format: Amir Hossein Mohseni, Sedigheh Taghinezhad-S, Pamela L. Beatty, Olivera J. Finn. Gut microbiota-derived metabolites as regulators of immunity in pre-cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 644.
Abstract 6442: Role of TWEAK-Fn14 axis in driving immunosuppression in glioblastoma multiforme
Authors: Beniwal Angad , Eghlimi Ryan , Alexander Kenneth D. , Blomquist Mylan R. , Tran Nhan 
Published: June 2023

Abstract
Cellular heterogeneity within glioblastoma multiforme (GBM) is a key driver of resistance to standard-of-care therapeutic approaches such as DNA damage (temozolomide, TMZ), angiogenesis inhibition (Bevacizumab, BM), radiation necrosis, and surgical resection. As such, understanding and targeting heterogeneous tumor-associated populations is a critical aim of ongoing GBM research. Central nervous system (CNS) resident microglia constitute significant percentages of primary GBM samples, often up to 50% of bulk tumor. Additionally, glioblastoma-associated microglia have been implicated in intra-tumoral immunosuppression, and are thus a key barrier to successful implementation of immunotherapies that seek to enhance T-cell mediated anti-tumoral cytotoxicity. As such, insight into targetable pathways that upregulate immunosuppressive cytokines within GBM-associated microglia is necessary for overcoming immuno-therapeutic failure. Here, we identify expression of the cytokine TWEAK (TNFSF12) and its receptor Fn14 (TNFRSF12A) within the myeloid compartment of primary GBM samples via scRNA-seq. Furthermore, we demonstrate TWEAK-mediated reprogramming of GBM-associated microglia towards an immunosuppressive phenotype capable of inhibiting CD8+ T cell activation and proliferation. These findings unveil a potent, targetable axis of immunosuppression within GBM and are thus an exciting step towards enhancing efficacy of existing T-cell based anti-cancer strategies for GBM patients.
Citation Format: Angad Beniwal, Ryan Eghlimi, Kenneth D. Alexander, Mylan R. Blomquist, Nhan Tran. Role of TWEAK-Fn14 axis in driving immunosuppression in glioblastoma multiforme [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6442.
Abstract 6448: Processed, red, and white meat consumption and breast composition in a prospective cohort study of Chilean girls
Authors: Kim Claire E. , Gaskins Audrey J. , Corvalan Camila , Pereira Ana , Shepherd John , Michels Karin B. 
Published: June 2023

Abstract
Meat consumption has been associated with risk of breast cancer. However, the association between different types of meat (processed and unprocessed red, and white) intake during childhood and breast density has not been explored. This prospective study included 290 Chilean girls from the Growth and Obesity Cohort Study. Diet was assessed every 6 months with a 24-hour recall. Dual-energy X-ray absorptiometry was used to assess breast density (absolute fibroglandular volume (FGV)) and percent breast density (FGV/total breast volume, %FGV) at Tanner Breast Staging 4 (B4). Multivariable linear regression models were adjusted for total calorie intake, age at B4, sugar sweetened beverage intake, vegetable intake, TV watching after school, highest maternal education level, BMI z-score, and height. Substitution analysis was assessed using white meat in replacement of processed and unprocessed red meat. There was no association between total, processed and unprocessed red, or white meat intake and %FGV and absolute FGV. In the estimated substitution analyses, we observed a slightly lower breast density when processed or unprocessed red meat was replaced with white meat; however, effect estimates were modest and imprecise. For example, substituting 1 serving of unprocessed white meat for 1 serving of processed or unprocessed red meat was associated -4.1 cm3 (95% CI -10.3, 2.2) and -4.5 cm3 (95% CI -10.3, 1.3) lower absolute FGV, respectively. In this cohort of Chilean girls, there was little association between total or specific types of meat intake and breast density.
Substitution analysis of different types of meat and average breast density at Tanner stage 4 Beta coefficient Confidence interval P value Absolute FGV (cm3) Substituting 1 serving of unprocessed white meat for 1 serving of unprocessed red meat -4.1 (-10.3, 2.2) 0.21 Substituting 1 serving of unprocessed white meat for 1 serving of processed red meat -4.5 (-10.3, 1.3) 0.13 Percentage FGV (%) Substituting 1 serving of unprocessed white meat for 1 serving of unprocessed red meat -2.5 (-5.9, 0.8) 0.14 Substituting 1 serving of unprocessed white meat for 1 serving of processed red meat -2.8 (-5.8, 0.3) 0.08
Citation Format: Claire E. Kim, Audrey J. Gaskins, Camila Corvalan, Ana Pereira, John Shepherd, Karin B. Michels. Processed, red, and white meat consumption and breast composition in a prospective cohort study of Chilean girls [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6448.
Abstract 6475: Compatibility of chatbot-based mobile and paper-based FFQs in participants with colorectal or gastric cancer screening
Authors: Lim Eui Yeon , Lim Yun Jeong , Kim Sang Hoon , Kim Woongsup , Lee Jung Eun 
Published: June 2023

Abstract
Background: The food frequency questionnaire (FFQ) is the most commonly used method to assess the usual diet of groups and individuals. Paper or electronic FFQ consists of frequencies and portion sizes of foods and beverages. We developed a chatbot-based mobile FFQ, by embedding the validated FFQs in KakaoTalk, Korea’s most popular mobile messenger. We examined the compatibility of the paper and chatbot-based mobile FFQs in participants who underwent cancer screening endoscopy.
Method: A total of 50 men and 45 women aged 24 to 79 were recruited from Dongguk University Ilsan Hospital between April and August 2022. Participants underwent gastroscopy or colonoscopy for cancer screening. They completed both the paper and chatbot-based mobile FFQs. Log-transformed intakes of energy and nutrients were compared using the Pearson correlation coefficient. We also calculated the Cohen’s Kappa coefficients and evaluated Bland-Altman plots and the percent agreement from cross-classification to assess the compatibility.
Results: The Pearson correlation coefficients of energy and energy-adjusted nutrients ranged from 0.74 (niacin) to 0.90 (vitamin A), and the median of coefficients was 0.85. Cohen’s kappa coefficient ranged from 0.56 (sodium) to 0.75 (n-6 fatty acid). In the Bland-Altman plots, most data were located between the lower and upper limits of agreement. The percentages of participants classified into the same and adjacent quartiles were between 88% and 98% for energy-adjusted nutrients.
Conclusions: Our study suggests a good compatibility of paper and chatbot-based mobile FFQs. The chatbot-based mobile FFQ may provide comparable intake rankings and be used to evaluate the association between dietary intake and disease risk in longitudinal studies.
Citation Format: Eui Yeon Lim, Yun Jeong Lim, Sang Hoon Kim, Woongsup Kim, Jung Eun Lee. Compatibility of chatbot-based mobile and paper-based FFQs in participants with colorectal or gastric cancer screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6475.
Abstract 6482: CLDN18.2 expression is associated with clinicopathological features and prognosis of Chinese patients with digestive system cancers: a retrospective analysis
Authors: XiaoYi Chong , Qi Changsong , Gong Jifang , Zhang Miao , Ma Mingyang , Jia keren , Zhou Ting , Jian Li , Peng Zhi , Xiao Jun , Peng Xiaohui , Liu Zhen , Li Zonghai , Zhang Xiaotian , Shen Lin 
Published: June 2023

Abstract
Importance: CLDN18.2 was a promising therapeutic target in solid tumors, whereas the clinicopathological features of Chinese CLDN18.2-positive cancer patients were rarely elucidated.
Objective: This study aimed to explore the association between CLDN18.2 expression and clinicopathological features of Chinese patients with CLDN18.2-positive digestive system cancers.
Methods: This retrospective study included digestive system cancer patients from June 2019 to April 2021 who were screened for two clinical trials of CT041 (an anti-CLDN18.2 CAR-T cell, NCT03874897, and NCT04581473), which were initiated at our center.
Results: A total of 875 digestive system cancer patients were included. CLDN18.2 expression was observed in 73.1% GC patients, 61.8% pancreatic cancer (PC) patients, 10.6% colorectal cancer (CRC) patients, and 65.6% biliary tract carcinoma (BTC) patients. In GC, CLDN18.2 expression was associated with age, sex, and Lauren phenotype (all P&lt;0.01). CLDN18.2-positive GC patients had a higher incidence of uterine adnexa metastasis (6.4% vs. 20.8%, P&lt;0.001), and a lower incidence of liver metastasis (22.2% vs. 35.7%, P&lt;0.001). In PC, CLDN18.2-positive cases had a higher proportion of tumors with moderate/high differentiation (46.1% vs. 19.0%, P&lt;0.001), compared with CLDN18.2-negative patients. Additionally, compared with CLDN18.2-negative patients, the proportion of right colon cancer was higher in CLDN18.2-positive patients (40% vs. 18.1%, P=0.028).
Conclusions: The results of this study suggested that CLDN18.2-positive tumors had unique clinicopathological features, which provided a theoretical basis for the treatment of CLDN18.2 positive tumors.
Citation Format: Chong XiaoYi, Changsong Qi, Jifang Gong, Miao Zhang, Mingyang Ma, keren Jia, Ting Zhou, Li Jian, Zhi Peng, Jun Xiao, Xiaohui Peng, Zhen Liu, Zonghai Li, Xiaotian Zhang, Lin Shen. CLDN18.2 expression is associated with clinicopathological features and prognosis of Chinese patients with digestive system cancers: a retrospective analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6482.