bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B013: Evaluation of anti-PD-L1 and anti-VEGF-A combinatorial immunotherapy in preclinical murine liver cancer models
Authors: Kam Shing , Ramadori Pierluigi , Fan Chaofan , Sagar Sagar , Heikenwälder Mathias 
Published: October 2024

Abstract
The combination of Atezolizumab (anti-PD-L1) plus Bevacizumab (anti-VEGF-A) is the most up-to-date FDA-approved first-line therapy for advanced stage hepatocellular carcinoma (HCC). Although this immune-oncology intervention showed better overall and progression-free survival, it only elicits a response in 20 – 30% of patients. Moreover, prognostic and predictive markers are currently unavailable, which renders patient stratification infeasible. In light of this obstacle, it is imperative to investigate the underlying mechanisms that drive therapeutic resistance. In this study, we aim to understand how genetic mutation background and etiology could impact therapeutic response. We evaluated the effects of anti-PD-L1 and anti-VEGF-A in different spontaneous liver cancer mouse models, with three gene-editing-based murine liver cancer models, and a diet-based murine metabolic dysfunction-associated steatohepatitis-induced HCC (MASH-HCC) model. The immunological landscape was examined with histological analysis, flow cytometry, and single-cell RNA sequencing (scRNA-seq). We demonstrated that the combinatorial immunotherapy significantly reduced tumor burden in c-Myc/Tp53-/--driven HCC, accompanied by an increase of CD8 T cells. However, the same therapy failed to inhibit tumor progression in KrasG12D/Tp53-/--driven combined hepatocellular and intrahepatic cholangiocarcinoma (cHCC-ICC), Ctnnb1T41A/c-Myc-driven HCC, and MASH-HCC, with a limited stimulation of CD4 and CD8 T cell infiltration and activation. Moreover, we found that the combinatorial immunotherapy induced an increase in tumor-associated neutrophils (TANs) in cHCC-ICC, and the auto-aggressive PD1+ CD8 T cell population in MASH- HCC, which likely take part in the development of therapeutic resistance. In summary, our findings suggest that both mutational background and etiology could influence the response of anti-PD-L1 and anti-VEGF-A combinatorial therapy, which might be attributed to the distinct immune microenvironment.
Citation Format: Shing Kam, Pierluigi Ramadori, Chaofan Fan, Sagar Sagar, Mathias Heikenwälder. Evaluation of anti-PD-L1 and anti-VEGF-A combinatorial immunotherapy in preclinical murine liver cancer models [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr B013.
Abstract B023: Immunomodulatory telodendrimer nanomedicine in treating ovarian cancer
Authors: Gadelrab Hadil A , Shi Changying , Guo Dandan , Hossan Md Shanewaz , Agarwal Rinki , Orsulic Sandra , Luo Juntao 
Published: October 2024

Abstract
Introduction: Despite the advances in ovarian cancer (OC) treatment, the 5-year survival rate is still lower than 40%. Surgery and chemotherapy can result in cellular debris and damage-associated molecular patterns (DAMPs) roaming the body, activating the immune cells, and causing inflammation, which has a key role in tumor progression. Despite the survival benefits of hyperthermic intraperitoneal chemotherapy (HIPEC) during the debulking surgery, magnified tissue damages lead to overwhelming inflammation. Inflammatory responses are triggered by the activation of toll-like receptors (TLRs) expressed on both immune and cancer cells to secret proinflammatory cytokines, which promote tumor proliferation and metastasis. Moreover, paclitaxel (PTX) and cisplatin (CDDP) can stimulate TLR-4, and several studies have shown that TLR-4 blockade can enhance the treatment effects. Therefore, tackling inflammation in cancer by inhibition of TLRs (e.g., TLR-2,4,9) is a current interest. We have developed a library of telodendrimer (TD) nanoparticles (NPs) with a flexible scaffold decorated with different charged and hydrophobic moieties for both therapeutic delivery and immune modulation via TLR inhibition. Thus, we hypothesize that treatment with immunomodulatory TDs, which inhibit TLR through direct targeting of receptors or through ligands (DAMPs) scavenging, can control chemotherapy/surgery-induced inflammation and the consequent tumor progression. Results and Methods: We have shown that TD can specifically inhibit TLR-4/2 activations upon stimulation with OC- sonicated DAMPs using HEK Blue TLR-4 and TLR-2 cells. TD can significantly inhibit proinflammatory cytokines in immune, OC cell lines and co-culture of OC and immune cells using ELISA. TD can inhibit the cell viability of SKOV-3 directly and upon stimulation with LPS, LTA, DAMPs, and conditioned media of THP-1 macrophages treated with LPS (TCM/LPS) using MTS assay. TD can inhibit the migration of OC cell lines in a dose-dependent manner using scratch assay. TD shows inhibition of NF-kB activation in OC cell lines. Moreover, a positively charged TD (ligands scavenger) shows preferential coating for wound sites and mitigation of the OC engraftment promoted by a surgical wound. Conclusion: We believe that TD's effective control of inflammation induced by OC treatment can reduce tumor progression. In the future, we will investigate loading TD with frontline chemotherapy (PTX and CDDP) for targeted delivery.
Citation Format: Hadil A Gadelrab, Changying Shi, Dandan Guo, Md Shanewaz Hossan, Rinki Agarwal, Sandra Orsulic, Juntao Luo. Immunomodulatory telodendrimer nanomedicine in treating ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr B023.
Abstract B027: Transcriptional and chromatin accessibility landscapes of hematopoietic progenitors in a mouse model of breast cancer
Authors: Fan Changxu , Wu Jun , Xing Xiaoyun , Barisas Derek A. G. , Choi Kyunghee , Wang Ting 
Published: October 2024

Abstract
Hematopoietic abnormalities, including myeloid-skewing, anemia, and extramedullary hematopoiesis, are often observed in cancer patients, with evidence suggesting that they promote the development of myeloid-derived suppressor cells. However, our understanding of the mechanisms underlying these hematopoietic phenotypes remains incomplete. Here, using the MMTV-PyMT mouse model of breast cancer, we characterize the transcriptional and chromatin accessibility landscapes of bone marrow and spleen hematopoietic progenitors using single-cell ATAC+RNA sequencing. We show that for the uncommitted hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (BM), tumor growth induces a moderate upregulation of the myeloid-bias transcriptional signature and no significant chromatin accessibility changes. Compared to BM HSPCs, spleen HSPCs do not show a further upregulation of the myeloid-bias signature, and instead show the signature of Notch signaling, which has been associated with erythroid commitment. In addition, we also identify a cluster of spleen HSPCs in tumor-bearing animals with a transcriptional signature of mobilization, while our paired chromatin data suggest that AP-1 factors play a key role in HSPC mobilization. Furthermore, in contrast to the subtle tumor-induced changes in BM HSPCs, prominent transcriptional and chromatin changes are observed in dendritic cell (DC) progenitors, consistent with known cancer-associated DC defects. Our chromatin data also confirms, in an unbiased manner, that Stat3 and CEBP are both key contributors to DC defects. Overall, we provide a comprehensive dataset for understanding the hematopoietic consequences of cancer.
Citation Format: Changxu Fan, Jun Wu, Xiaoyun Xing, Derek A. G. Barisas, Kyunghee Choi, Ting Wang. Transcriptional and chromatin accessibility landscapes of hematopoietic progenitors in a mouse model of breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr B027.
Abstract B053: Neoadjuvant Personalized Viral Vectored vaccines are highly effective against tumor relapse in checkpoint inhibitor resistant murine models
Authors: D'Alise Anna Morena , Seclì Laura , Nocchi Linda , Leoni Guido , Cotugno Gabriella , Troise Fulvia , Micarelli Elisa , Garzia Irene , Antonucci Laura , Scarselli Elisa 
Published: October 2024

Abstract
Personalized vaccines targeting tumor neoantigens represent a promising avenue in cancer immunotherapy. The optimal setting for a cancer vaccine to work is at early stage of disease, as vaccination at this stage is expected to elicit potent and effective anti-tumor immunity. Checkpoint inhibitors (CPIs) have demonstrated a potent clinical outcome when used in adjuvant setting after tumor resection. More recently, the neoadjuvant use of CPI prior to tumor resection has been shown to be superior to the adjuvant treatment. Neoadjuvant immunotherapy offers the advantage of immunological priming while the primary tumor is still in place triggering a more robust immune response that may be beneficial in preventing tumor relapse. In this context, neoantigen-based vaccines can also be used in adjuvant or neoadjuvant settings. Here, we investigated the use of a multiepitope vaccine targeting tumor neoantigens selected from the B16F10 tumor model as adjuvant and neoadjuvant treatment, alone and in combination with anti-PD1. Neoantigen vaccination in neoadjuvant setting was highly effective as monotherapy providing ∼ 90% protection against tumor relapse post-surgery. Adjuvant vaccination was not effective as monotherapy in this model, requiring combination with anti-PD1 to prevent tumor relapse. The activity of neoadjuvant vaccination was CD8 dependent, as depletion of CD8+ T cells abrogated the anti-tumor activity with relapse rates comparable to untreated mice. In this setting, strong induction of neoantigen specific T cells was observed persisting post-surgery. These findings underscore the potential of neoadjuvant vaccination to provide protection from tumor recurrence and improving patients’ outcomes, offering exciting prospects in this clinical setting.
Citation Format: Anna Morena D'Alise, Laura Seclì, Linda Nocchi, Guido Leoni, Gabriella Cotugno, Fulvia Troise, Elisa Micarelli, Irene Garzia, Laura Antonucci, Elisa Scarselli. Neoadjuvant Personalized Viral Vectored vaccines are highly effective against tumor relapse in checkpoint inhibitor resistant murine models [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr B053.
Abstract B054: Enhanced Antitumor Efficacy of Oncolytic Adenovirus Co-Expressing IL-12 and shVEGF Combined with Anti-PD-1 in Renal Cell Carcinoma
Authors: Kim Yunlim , Yoon A-Rum , Yun Chae-Ok , Kim Choung-Soo , Lim Bumjin 
Published: October 2024

Abstract
Despite advancements in treatment modalities such as surgery, chemotherapy, and immunotherapy, resistance remains a formidable challenge in effectively managing renal cell carcinoma (RCC). Although combination therapy with immune checkpoint inhibitors is recommended as a first-line treatment for metastatic renal cell carcinoma (mRCC), it often induces a high incidence of immune-mediated adverse effects. Recently, oncolytic adenoviruses have emerged as promising agents that can enhance the tumor microenvironment and stimulate tumor-specific T cell responses. Therefore, we evaluated the antitumor efficacy of oAd/IL-12/shVEGF—an oncolytic adenovirus co-expressing cytokine interleukin-12 (IL-12) and short hairpin RNA targeting vascular endothelial growth factor (shVEGF)—as a monotherapy and in combination with anti-PD-1 in a renal cell carcinoma mouse model. To investigate the therapeutic potential of oAd/IL-12/shVEGF, we evaluated its efficacy as a monotherapy in a xenograft A498 mouse model and in combination with anti-PD-1 in a syngeneic RENCA mouse model. Tumor-bearing mice were injected intratumorally with oAd/IL-12/shVEGF when the tumors reached 100-200mm³. Tumor volume and body weight were recorded until the end of the experiment. Mice were sacrificed when the tumors reached 1800mm³, and the tumors were disaggregated. To further evaluate the anti-tumor efficacy mediated by oAd/IL-12/shVEGF, tumor tissues were examined for proliferation marker (PCNA), adenovirus injection marker (E1A), and anti-tumor immune marker (CD4/CD8) by H&E and immunohistochemical analysis. In the A498 xenograft mouse model, the oAd/IL-12/shVEGF monotherapy group demonstrated significant tumor growth suppression compared to the PBS-treated group. Additionally, in the RENCA RCC syngeneic mouse model, superior antitumor effects were observed in the group treated with the combination of oAd/IL-12/shVEGF and anti-PD-1 compared to the groups treated with oAd/IL-12/shVEGF or anti-PD-1 alone.
Citation Format: Yunlim Kim, A-Rum Yoon, Chae-Ok Yun, Choung-Soo Kim, Bumjin Lim. Enhanced Antitumor Efficacy of Oncolytic Adenovirus Co-Expressing IL-12 and shVEGF Combined with Anti-PD-1 in Renal Cell Carcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr B054.
Abstract B058: Nous-209 off-the-shelf vaccine targets neoantigens mutations well represented both in primary and metachronous incident CRCs from Lynch syndrome patients
Authors: De Marco Lorenzo , Micarelli Elisa , Panula Joni , D'Alise Anna Morena , Leoni Guido , Hokkanen Kalle E. , Hämäläinen Eija , Mecklin Jukka-Pekka , Scarselli Elisa , Seppälä Toni 
Published: October 2024

Abstract
Lynch Syndrome (LS) is the most common hereditary cancer syndrome, caused by germline mutations in one of the four DNA mismatch repair (MMR) genes. LS patients have a high risk to develop microsatellite instable (MSI) colorectal cancers. Tumors developed by LS carriers display high levels of microsatellite instability, which leads to the accumulation of large numbers of mutations, among which frameshift insertion/deletions (indels) within microsatellite (MS) loci are very common and shared among different tumors. When indels occur in coding genes they give rise to frameshift peptides (FSPs) with a very high potential to act as safe and potent neoantigens for a vaccine. NOUS-209 is a genetic vaccine encoding 209 neoantigens, shared across sporadic and hereditary MSI tumors, developed for interception and treatment of MSI tumors. Phase 1b trial evaluating NOUS-209 monotherapy in healthy LS carriers showed the induction of a potent and broad immune response. Here, we characterize indels encoding FSPs in a cohort of 50 incident MSI CRC from LS patients detected during routine screening (38 primary tumors; 22 metachronous tumors) by whole Exomeseq NGS. Overall, primary and metachronous tumors have a similar number of indels in coding genes. The repertoire of detected indels is only partially shared (27%) between the two categories of tumors. The 209 indels selected for the NOUS-209 vaccine are instead highly shared (95%) between primary and metachronous tumors. Moreover, the analysis of 8 patients for which both the primary and the metachronous tumor were available confirmed the presence of the 209 mutations both in the first and the second tumor. Therefore, the NOUS 209 vaccine has the potential to prevent tumor occurrence both in previvors and survivors by inducing a broad T cell immune response against recurrent FSP.
Citation Format: Lorenzo De Marco, Elisa Micarelli, Joni Panula, Anna Morena D'Alise, Guido Leoni, Kalle E. Hokkanen, Eija Hämäläinen, Jukka-Pekka Mecklin, Elisa Scarselli, Toni Seppälä. Nous-209 off-the-shelf vaccine targets neoantigens mutations well represented both in primary and metachronous incident CRCs from Lynch syndrome patients [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr B058.
Abstract IA01: Dumpster-diving into the cancer degradome
Authors: Merbl Yifat 
Published: October 2024

Abstract
Recently, we uncovered a pivotal role for altered proteasome complex composition in shaping tumor immunogenicity in non-small cell lung cancer (NSCLC). Our research demonstrated that the upregulation of a regulatory cap of the proteasome, PSME4, leads to a reduction in antigenic diversity through alterations in proteasomal cleavage patterns, consequently impeding T-cell-mediated anti-tumor immunity. These findings underscore the importance of probing the tumor degradome and its implications for tumor-immune interactions. Yet, numerous questions remain unanswered: Do specific substrates exhibit preferential degradation in PSME4-capped proteasomes? What constitutes their recognition signal? And fundamentally, how do alterations in the degradation landscape influence tumor inflammation? In my talk, I will delve into our latest advancements in addressing these questions, offering insights into the intricate interplay between proteasome-mediated degradation, tumor inflammation, and STAT signaling.
Citation Format: Yifat Merbl. Dumpster-diving into the cancer degradome [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr IA01.
Latrophilin-2 Deletion in Cardiomyocyte Disrupts Cell Junction, Leading to D-CMP
Authors: Kang Minjun , Lee Choon-Soo , Son HyunJu , Lee Jeongha , Lee Jaewon , Seo Hyun Ju , Kim Moo-Kang , Choi Murim , Cho Hyun-Jai , Kim Hyo-Soo 
Published: October 2024

BACKGROUND:
Latrophilin-2 (Lphn2), an adhesive GPCR (G protein-coupled receptor), was found to be a specific marker of cardiac progenitors during the differentiation of pluripotent stem cells into cardiomyocytes or during embryonic heart development in our previous studies. Its role in adult heart physiology, however, remains unclear.

METHODS:

The embryonic lethality resulting from
Lphn2
deletion necessitates the establishment of cardiomyocyte-specific, tamoxifen-inducible
Lphn2
knockout mice, which was achieved by crossing
Lphn2
flox/flox
mice with mice having MerCreMer (tamoxifen-inducible Cre [Cyclization recombinase] recombinase) under the α-myosin heavy chain promoter.

RESULTS:

Tamoxifen treatment for several days completely suppressed Lphn2 expression, specifically in the myocardium, and induced the dilated cardiomyopathy (D-CMP) phenotype with serious arrhythmia and sudden death in a short period of time. Transmission electron microscopy showed mitochondrial abnormalities, blurred Z-discs, and dehiscent myofibrils. The D-CMP phenotype, or heart failure, worsened during myocardial infarction. In a mechanistic study of D-CMP,
Lphn2
knockout suppressed PGC-1α (Peroxisome proliferator-activated receptor gamma coactivator 1-alpha) and mitochondrial dysfunction, leading to the accumulation of reactive oxygen species and the global suppression of junctional molecules, such as N-cadherin (adherens junction), DSC-2 (desmocollin-2; desmosome), and connexin-43 (gap junction), leading to the dehiscence of cardiac myofibers and serious arrhythmia. In an experimental therapeutic trial, activators of p38-MAPK (p38 mitogen-activated protein kinases), which is a downstream signaling molecule of Lphn2, remarkably rescued the D-CMP phenotype of
Lphn2
knockout in the heart by restoring PGC-1α and mitochondrial function and recovering global junctional proteins.

CONCLUSIONS:
Lphn2 is a critical regulator of heart integrity by controlling mitochondrial functions and cell-to-cell junctions in cardiomyocytes. Its deficiency leads to D-CMP, which can be rescued by activators of the p38-MAPK pathway.
Introduction to Abraham Serfaty’s ‘Letter to the Damned of Israel’
Authors: Nadi Selim 
Published: October 2024

Abstract
This article introduces Abraham Serfaty’s ‘Letter to the Damned of Israel’, written in 1982 while he was imprisoned. Serfaty, a Jewish-Moroccan Marxist, reflects on antisemitism, anti-Zionism, and the oppression of both Palestinians and Jews by Zionism. This introduction explores Serfaty’s political thoughts on the relationship between Palestinian liberation, Zionism, and the Jewish Question. It highlights his belief in the importance of Arab-Jewish identity and the role of Arab Jews in the anti-Zionist struggle. ​It also discusses Serfaty’s engagement with various international issues and his influence on the Moroccan leftist movement, particularly through his involvement with the Marxist-Leninist organisation Ila Al Amam and the journal Souffles. ​
Johanna Helena Herolt, Alida Withoos, and artistic exchanges
Authors: Powell-Warren Catherine 
Published: October 2024

Abstract
For a Dutch woman in the second half of the seventeenth century, developing a career illustrating natural history – a field that was becoming increasingly institutionalized – posed a number of challenges related to gendered social, economic, and cultural expectations and limitations. Yet, Johanna Helena Herolt and Alida Withoos established themselves as leading figures in this specialized genre. This essay examines the similarities in the works of the two artists, with a view to gaining insight into the circumstances of their production. In light of the inapplicability and inflexibility of traditional art historical concepts such as collaboration and influence, it proposes conceiving of Herolt and Withoos as engaged in a trading zone consisting of a few, highly engaged experts, amateurs, and artists, in which knowledge, ideas, and artistic practices could be exchanged freely and deployed towards the completion of collective projects, such as Agnes Block’s florilegia and the Moninckx Atlas.
Unmarried, married, widowed or dead
Authors: Vlaardingerbroek Pieter 
Published: October 2024

Abstract
This article focusses on Dutch women as commissioners of architecture between 1680 and 1800 and especially on women from the merchant’s classes. Its aim is to demonstrate that women – despite their status of being legally incapacitated – were able to erect some of the most stupendous canal houses in Amsterdam. This seems to be a contrast with English noble women during the Georgian period. Female propriety was translated into piety, or humility, charity and virtue, resulting in a more modest kind of architecture. Dutch merchant’s women were not subdued by these notions at all: their houses rank among the most ornamented and richest houses in Holland.