bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4401: The precision chemotherapy to improve the epithelial ovarian cancer prognosis
Authors: Pak Seongeun , Choi Youn Jin 
Published: April 2023

Abstract
Purpose: Recurrence is common in ovarian cancer patients, even in those patients who show complete response after first-line chemotherapy, 80% of the patients experience a recurrence. So gynecologic oncologists often have to consider several factors when choosing next chemotherapy regimen. Therefore, this study aimed to find serial chemotherapy regimen choice to anticipate patients’ better prognosis.
Materials and Methods: We reviewed 656 patients diagnosed ovary cancer in one tertiary institutional hospital between 2006 and 2020. Patents’ clinic-pathologic characteristics, primary treatment, chemotherapy regimens, survival outcomes were collected. We divided patients into several groups according to their chemotherapy regimen by mechanism of action and compared them. 1st line chemotherapy(CTx) type 1: carboplatin-paclitaxel, carboplatin-docetaxol, cisplatin-paclitaxel, cisplatin-docetaxol2nd line CTx type 1: carboplatin-paclitaxel, carboplatin-docetaxol, cisplatin-paclitaxel, cisplatin-docetaxol2nd line CTx type 4: carboplatin-gemcitabine2nd maintenance CTx type 2: PARP inhibitor(PARPi)2nd line CTx Type 5: Platinum + topoisomerase inhibitor 2nd line CTx Type 6(cisplatin-vinorelbine)2nd line CTx Type 8(topoisomerase inhibitor only) 2nd line CTx Type12 (single taxol) The survival rate of ovary cancer patients decreased from stage 1 to stage 4.Among 1st line CTx type 1 and 2nd line CTx type(1 or 4) patients, those who used PARPi in 2nd line maintenance CTx(n=14) had a higher death rate than those who did not receive maintenance CTx or received that other than PARPi(hazard ratio 1.44). In the 1st line CTx 1~4 group, we divided patients according to 2nd line CTx type. We compare 2nd line CTx type 5 group(n=30) with type 6+8+12 group(n=26). The death rate was of type 5 group was higher than type 6+8+12 group. And Overall survival of 2nd line CTx type 5 group was 22 months, that of 2nd line CTx type 6+8+12 group was 26 months.
Conclusion: When changing the chemotherapy regimen in the recurrence of ovarian cancer, the survival rate or overall survival may vary depending on the order in which the regimen is used. If we collect patients data more broadly, the predictive power will be better.
Citation Format: Seongeun Pak, Youn Jin Choi. The precision chemotherapy to improve the epithelial ovarian cancer prognosis. [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 4401.
Abstract 4403: The Efficacy of Immune Checkpoint Inhibitors in Advanced Biliary Tract Cancer with KRAS Mutation
Authors: Jeong Sun Young , Jang Jaeyeon , Jeon Youngkyung , Jung Ye Ji , Choi Daeho , Hong Joohyun , Kim Seung Tae , Hong Jung Yong , Park Joon Oh , Park Young Suk , Lim Ho Yeong 
Published: April 2023

Abstract
BackgroundWith a 15% of incidence, KRAS is one of the most common mutations in biliary tract cancer (BTC) and a poor prognostic factor. In BTC, the immune checkpoint inhibitor (ICI) as salvage therapy has modest activity. There was little data on the efficacy of ICIs according to the status of KRAS mutation in BTC.
MethodWe conducted molecular profiling in BTC patients who received the ICIs as salvage therapy. Programmed death ligand 1 (PD-L1) expression on tumor cells and tumor-infiltrating lymphocytes (TIL) was also assessed. We analyzed overall survival (OS) and progression-free survival (PFS) of ICI in BTC patients according to the status of PD-L1 expression and KRAS mutation.
ResultA total of 62 patients were included in this analysis. The median age was 68.0. 47 patients (75.8%) received pembrolizumab and 15 (24.2%) received nivolumab as salvage therapy. All patients received gemcitabine plus cisplatin as the frontline therapy, and 53.2% had fluoropyrimidine plus oxaliplatin (FOLFOX) before ICIs. The median lines of prior chemotherapy were 2.5. KRAS mutation was found in 14 patients (22.6%). 28 patients (45.2%) were positive for PD-L1 CPS. There was no statistical correlation between the status of KRAS mutation and PD-L1 expression. The median OS and PFS to ICI were 5.6 (IQR; 3.3 - 8.0) and 3.8 (IQR; 3.0 - 4.5) months, respectively. There were no statistically significant differences in PFS to ICIs according to the status of KRAS mutation (Mutant type vs. Wild type) and PD-L1 expression (Positive vs Negative). In subgroup analysis, patients with both KRAS mutation and PD-L1 positivity had longer PFS as compared to patients with KRAS mutation and PD-L1 negativity (6.5 vs 2.6 months, p=0.047). This finding was not shown in patients with a wild type of KRAS.
ConclusionThis analysis showed that PD-L1 expression might be a novel biomarker for ICIs in BTC patients with KRAS mutation but not the wild type of KRAS.
Citation Format: Sun Young Jeong, Jaeyeon Jang, Youngkyung Jeon, Ye Ji Jung, Daeho Choi, Joohyun Hong, Seung Tae Kim, Jung Yong Hong, Joon Oh Park, Young Suk Park, Ho Yeong Lim. The Efficacy of Immune Checkpoint Inhibitors in Advanced Biliary Tract Cancer with KRAS Mutation. [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 4403.
Abstract 4433: Galectin-3 synergizes with CD47 to suppress phagocytosis and T cell immunity in peritoneal metastases of gastric adenocarcinoma
Authors: Fan Yibo , Song Shumei , Li Yuan , Dhar Shilpa , Jin Jiankang , Yao Xiaodao , Wang Ruiping , Wang Ailing , Pizzi Melissa Pool , Wu Jingjing , Yoshimura Katsuhiro , Ma Lang , Hanash Samir , Calin George , Wang Linghua , Curran Michael , Ajani Jaffer 
Published: April 2023

Abstract
Peritoneal metastasis (PC), the common sites of gastric adenocarcinoma (GAC) metastasis, remains resistant to therapies available in the clinics and new target is strived to be found. CD47 is one of the major players in conveying the “don’t eat me” signal upon binding its receptor SIRPα on myeloid cells which evade innate immune responses. Previously clinical studies on the blockade of CD47 alone resulted in limited clinical benefits suggesting that other target(s) must be inhibited simultaneously with CD47 for gaining advantage. Here, we found that CD47 was highly expressed on peritoneal malignant cells and its overexpression was a poor prognosticator. Additionally, we observed that Galectin-3 (Gal-3) was highly enriched in tumor cluster and was positively correlated with CD47 expression in short survival of patients revealed by scRNA-seq and metastatic GAC samples. Moreover, we found double positive of Gal-3 and CD47 significantly associated with diffuse type, poor differentiation, and tumor relapse. Mechanistically, Depletion of Gal-3 in mouse tumor and human tumor cells reduced the levels of CD47 through inhibition c-Myc expression and its binding to the promoter of CD47. Additionally, tumor-derived Gal-3 were found critical for tumor progression accompanied with protected GAC cells from phagocytosis by macrophages. Gal-3 deficiency resulted in a marked reduction in M2 macrophages and elevated T cell effector activity. Dual blockade of Gal-3 and CD47 significantly decreased tumor growth by promoted phagocytosis, repolarization of macrophage and boosted T cell immune responses in the tumor microenvironment. Our data uncover that Gal-3 synergizes with CD47 to suppress phagocytosis and orchestrates immunosuppressed milieu in the tumor microenvironment warrants combination therapeutic strategy in GAC patients with peritoneal metastases.
Citation Format: Yibo Fan, Shumei Song, Yuan Li, Shilpa Dhar, Jiankang Jin, Xiaodao Yao, Ruiping Wang, Ailing Wang, Melissa Pool Pizzi, Jingjing Wu, Katsuhiro Yoshimura, Lang Ma, Samir Hanash, George Calin, Linghua Wang, Michael Curran, Jaffer Ajani. Galectin-3 synergizes with CD47 to suppress phagocytosis and T cell immunity in peritoneal metastases of gastric adenocarcinoma. [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 4433.
Abstract 444: Inhibition of GPR68 signaling activated downstream of the Warburg effect induces cell death and enhances radiosensitivity in diverse cancer cell types
Authors: Neitzel Leif R. , Lee Han G. , Shukla Hem , Mahmood Javed , Williams Charles H. , Hong Charles C. 
Published: April 2023

Abstract
Introduction: The Warburg effect, a phenomenon in which cancer cells produce energy via aerobic glycolysis, is a hallmark of cancer. A key physiological consequence of the Warburg effect is lactate secretion, which acidifies the tumor milieu, thought to confer tumor resistance to chemotherapy and radiotherapy. Yet, the molecular mechanism of this resistance is not well understood. Ogremorphin, a small molecule inhibitor of an extracellular pH sensing receptor, GPR68, was found to inhibit the growth and survival of Glioblastomas. However, the consequences of GPR68 inhibition on carcinomas alone and in combination with radiation are unclear. The aim of this study was to investigate the effect of ogremorphin alone and in combination with radiation on multiple cancer cell lines.
Methods: 1) siRNA and CRISPR-interference knockdown of GPR68 in two carcinoma cell lines Panc02 (pancreatic ductal adenocarcinoma) and A549 (lung cell carcinoma). 2) Treatment of pancreatic and lung carcinomas with GPR68 inhibitor ogremorphin alone and with ionizing radiation. 3) Cell viability (MTT), clonogenic assays, and cell cycle analysis via flow cytometry were performed. 4) Lipid peroxidation study for induction of ferroptosis. The interaction between ogremorphin and radiation was evaluated using the combination index.
Results: Knockdown of GPR68 had significant effects on cell survival. Exposures of ogremorphin in clonogenic assays indicated a significant effect in reducing colony size, but not on the number of colonies, in both carcinoma cell lines. Moreover, ogremorphin significantly increased the efficacy of irradiation on the reduction of colony size. Although ogremorphin had no effect on cell cycle alone, it had a synergistic increase in G2 phase cells with radiation. Finally, GPR68 inhibition indicated synergistic activity with radiation for the induction of ferroptosis.
Conclusion. GPR68 inhibition induces ferroptosis in cancer cells on its own, but also synergistically with ionizing radiation. This study suggests that GPR68 is a key cancer survival pathway activated by the acidic tumor milieu/Warburg effect, and that the ogremorphin class of molecules may be suitable candidates for combination therapy in lung and pancreatic carcinoma.
Citation Format: Leif R. Neitzel, Han G. Lee, Hem Shukla, Javed Mahmood, Charles H. Williams, Charles C. Hong. Inhibition of GPR68 signaling activated downstream of the Warburg effect induces cell death and enhances radiosensitivity in diverse cancer cell types [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 444.
Abstract 4449: The expression and immune regulation of thymic stromal lymphopoietin in non-small cell lung cancer development and progression
Authors: Chen Chung-Yu , Chen Ying-Yin , Peng Hung-Chueh , Ye Yi-Ling 
Published: April 2023

Abstract
Purpose: Previous studies have shown thymic stromal lymphopoietin (TSLP) to be an important driver of type 2 inflammation. A new and unexpected function for TSLP has been found in the induction and progression of a variety of tumors. This study conducted TSLP performance in lung cancer patients and the correlation of the clinical pathological data.
Materials and Methods: The patients with pathological diagnosis of lung cancer were enrolled. The percentage of CD19 + B cells was determined in the lymphocyte gate and counted via flow cytometry. Relevant serum cytokines including TSLP were analyzed using LEGENDplex software. In vitro study was conducted by A549 cell line and the mRNA expression change of TSLP was extracted by Reverse Transcriptase PCR (RT-PCR).
Results: When comparing the frequencies of B cell subsets between early-stage (N = 31) and late-stage lung cancer group (N = 29), the frequency of memory B cell (17.3±6.1% vs 23.4±15.1%, p=0.042), CD27+IgM+ B cell (1.8±1.3% vs 2.9±2.3%, p=0.030), class-switched B cell (15.5±5.5% vs 22.2±14.9%, p=0.023), class-switched memory B cell (69.9±11.3% vs 59.9±19.7%, p=0.017) and plasmablast (8.5±7.3% vs 18.0±20.8%, p=0.019) were significantly different between groups. The patients with higher frequency of class-switched B cell had significantly worse prognosis than low frequency (HR 3.054, 95% CI 1.007-9.262, p=0.049). The level of IL-1B, IL-6, IL-10, IL-12, IL-13, and TSLP were significantly higher in the late-stage cancer patients. Simulation in vitro test with human lung A549 cell line was performed, the expression of short-form TSLP (sfTSLP) level decreased with the higher anti-cancer drug as Pemetrexed concentration.
Conclusions: The increase proportion of CD27+CD38- (class-switched) B cell could be an independent, poor prognostic factor for NSCLC patients. TSLP signaling is addressed to the anti-cancer therapeutic response. Therefore, TSLP and relevant cytokines may be involved directly and indirectly in shaping the inflammatory status of the tumor microenvironment.
Citation Format: Chung-Yu Chen, Ying-Yin Chen, Hung-Chueh Peng, Yi-Ling Ye. The expression and immune regulation of thymic stromal lymphopoietin in non-small cell lung cancer development and progression. [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 4449.
Abstract 4462: Immunoregulatory effects of NNMT-expressing cancer-associated fibroblasts
Authors: Heide Janna , Piffko Andras , Bilecz Agnes J. , Teich Ethan A. , Schweizer Lisa , Alhunayan Sayed R. , Yang Kaiting , Lengyel Ernst 
Published: April 2023

Abstract
Nicotinamide N-methyltransferase (NNMT) is highly expressed in the stroma of several malignancies and has been shown to drive the transformation of resting fibroblasts into cancer-associated fibroblasts (CAFs) through epigenetic changes. Given that CAFs can promote immunosuppression in cancer, the aim of our study was to investigate the effect of NNMT-expressing CAFs on the tumor-immune environment.
Using a co-culture system of normal fibroblasts and activated PBMCs, we found that IFN-γ produced by PBMCs upregulates NNMT expression in fibroblasts. We confirmed this mechanism in vivo in IFN-γ knockout mice and identified T cells as the main source of IFN-γ in the tumor. Gene expression and protein analysis showed that upregulation of NNMT in CAFs induces the secretion of the chemokine CXCL1, a critical chemoattractant for immunosuppressive myeloid-derived suppressor cells (MDSCs). Upregulation of NNMT induces CXCL1 secretion directly through promoter hypomethylation, and in vitro migration assays show that NNMT-expressing CAFs recruit high numbers of MDSCs. Using spectral flow cytometry, we analyzed the tumor-immune cell infiltration in whole-body NNMT-knockout mice and discovered that NNMT knockout of the stroma significantly reduced the abundance of MDSCs and increased the number of functional CD8+ T cells. Increased T cell cytotoxicity was associated with a significant reduction in tumor burden in the syngeneic ID8 ovarian and MC38 colon cancer models. These findings were confirmed after adoptive transfer of NNMT-wildtype immune cells into irradiated whole-body NNMT-knockout mice. Moreover, in scRNA-seq data of various human malignancies, we found a strong correlation between NNMT and CXCL1 expression in CAFs.
In summary, our results support a model in which cancer cells induce IFN-γ secretion by T-cells, thereby upregulating NNMT expression in fibroblasts, leading to CXCL1 secretion. CXCL1 secreted by CAFs recruits MDSCs to the tumor, which in turn suppress the anti-tumor T cell response.
Citation Format: Janna Heide, Andras Piffko, Agnes J. Bilecz, Ethan A. Teich, Lisa Schweizer, Sayed R. Alhunayan, Kaiting Yang, Ernst Lengyel. Immunoregulatory effects of NNMT-expressing cancer-associated fibroblasts. [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 4462.
Abstract 4464: Comparison of two DTH models for T cell-mediated immunity in preclinical screen
Authors: Cai Yingying 
Published: April 2023

Abstract
Introduction: Delayed-type hypersensitivity (DTH) involves the recruitment of T cells into tissues and the activation by antigen-presenting cells to produce cytokines, which further activates local endothelial cells and recruits macrophages, resulting in tissue erythema, swelling and inflammation. DTH models in mice are classical in-vivo T cell-mediated immunity screening models for atopic dermatitis, asthma and autoimmune diseases. Different antigens and haptens have been used to establish DTH models with different Th1/Th2 profiles. More immunity characterization of the most widely used DTH models need to be revealed.
Results: We established DNFB, Oxazolone induced DTH models in both BALB/c and C57BL/6 mice with ear thickness as the readout. At the termination, we measured Th1 (ie, IFN-γ)/Th2 (ie, IL-4) profile, pro-inflammatory cytokines including IL-13, TNF, and IL-17 as well as myeloperoxidase (MPO) activity from mice ears as indices to score the degree of inflammation. Oxazolone in BALB/c exhibited more repeatable and robust window in Th1/Th2 balance and cytokines profiles. The comparison of two DTH models were further validated by the pathological analysis for cell infiltration in mouse ears and immune-phenotyping in spleen by FACS.
Conclusion: The comparison of DNFB and Oxazolone induced DTH models characterized the disease progression and established a more comprehensive preclinical DTH model with well-defined Th1/Th2 profile for the drug efficacy evaluation in the T cell-mediated immune response.
Key words: Delayed-type hypersensitivity, mice model, T cell-mediated
Citation Format: Yingying Cai. Comparison of two DTH models for T cell-mediated immunity in preclinical screen. [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 4464.
Abstract 4465: Evaluation of tumor draining lymph nodes in dogs with spontaneously arising osteosarcoma using single-cell sequencing
Authors: Brill Samuel A. , Ammons Dylan T. , Avery Anne C. , Thamm Douglas H. 
Published: April 2023

Abstract
Tumor draining lymph nodes (TDLNs) function as an anatomic niche which primes immune cells to generate anti-cancer responses. While tumors are frequently staged based on the presence or absence of TDLN metastasis, mechanisms for how tumors impact the TDLN microenvironment and immunologic responses are incompletely understood. Dogs with spontaneously arising tumors provide an opportune model to study immuno-oncology, sharing many similarities to human patients with their environment, clinical care, and pathobiology. To evaluate how tumors impact TDLN responses, we conducted single cell RNA sequencing (scSeq) on cryopreserved TDLNs of dogs with osteosarcoma (n=4) and healthy controls (n=2). We obtained an average of 3,984 cells per sample (range 1,603-5,259) with a total of 4,780 cells from healthy samples and 19,121 cells from TDLN samples. All samples were integrated into one dataset, then unsupervised clustering was completed. Each unique cell cluster was assigned an identity using canonical markers and reference mapping to human datasets. Following cell classification, we observed notable changes in gene expression across all cells isolated from the LNs, with most differences arising from changes to the transcriptome of myeloid cells. Although still preliminary, the data also demonstrate differences in the abundance of T, B, and myeloid cells between healthy and tumor draining LNs. Taken together, this dataset provides indications of the changes TDLNs undergo in dogs with osteosarcoma.
Citation Format: Samuel A. Brill, Dylan T. Ammons, Anne C. Avery, Douglas H. Thamm. Evaluation of tumor draining lymph nodes in dogs with spontaneously arising osteosarcoma using single-cell sequencing. [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 4465.
Abstract 4588: Vascular regulation of T-cell exclusion in melanoma
Authors: Park Ha-Ram , Shiva Anahita , Cummings Portia , Carvajal Richard , Thurston Gavin , An Joon-Yong , Lund Amanda W. , Yang Hee Won , Kim Minah 
Published: April 2023

Abstract
T-cell position in the tumor microenvironment determines the probability of target encounter and tumor killing. CD8+ T-cell exclusion from the tumor parenchyma is associated with poor response to immunotherapy and yet the biology that underpins this distinct pattern remains unclear. Here we show that the vascular destabilizing factor angiopoietin-2 (ANGPT2) causes compromised vascular integrity in the tumor periphery, leading to impaired T-cell infiltration within tumor. We analyzed the spatial regulation of ANGPT2 in whole tumor cross-sections and its impact on CD8+ T-cell position, vascular integrity, and response to immunotherapy using syngeneic murine melanomas. We found that T-cell exclusion was associated with peritumoral expression of ANGPT2 and elevated vascular leakage in human and murine melanomas. Both pharmacological and genetic blockade of ANGPT2 promoted CD8+ T-cell infiltration to the tumor core, exerting antitumor effects. Importantly, the reversal of T-cell exclusion following ANGPT2 blockade not only enhanced response to anti-PD-1 therapy in immunogenic, therapy responsive mouse melanomas, but also rendered non-responsive tumors susceptible. Therapeutic response after ANGPT2 blockade, driven by improved CD8+ T-cell infiltration, coincided with TIE2 signaling activation and increased vascular integrity in the tumor periphery, indicating that maintenance of vascular integrity within tumors is necessary for robust response to immunotherapy. These data highlight ANGPT2/TIE2 signaling as a key mediator of T-cell exclusion and a promising target to potentiate checkpoint inhibitor efficacy in melanoma.
Citation Format: Ha-Ram Park, Anahita Shiva, Portia Cummings, Richard Carvajal, Gavin Thurston, Joon-Yong An, Amanda W. Lund, Hee Won Yang, Minah Kim. Vascular regulation of T-cell exclusion in melanoma. [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 4588.