tbuckley/cabot-search huggingface dataset:
Abstract PO2-24-12: Tumor-specific circRNAs elicit anti-tumor immune response via encoding cryptic antigenic peptides
Authors: Di Huang, Jianing Chen, Shicheng Su, Erwei Song
Journal: Cancer Research (2024)

Abstract Emerging data have shown that previously defined noncoding genomes might encode human leukocyte antigen (HLA) binding peptides as cryptic antigens to stimulate adaptive immunity. However, the significance and mechanisms of cryptic antigens in anti-tumor immunity remain unclear. Here, mass spectrometry for HLA class I (HLA-I) peptidome coupled with ribosome sequencing of human breast cancer samples identified HLA-I binding cryptic antigenic peptides, which were noncanonically translated by a tumor-specific circular RNA CEIP (circCEIP). Importantly, the cryptic peptides efficiently primed naive CD4+ and CD8+ T cells in an antigen-specific manner and elicited anti-tumor immunity. Clinically, the expression of circCEIP and its encoding peptides was associated with massive infiltration of antigen-specific CD8+ T cells and better survival of breast cancer and melanoma patients. Mechanistically, circCEIP-encoding peptides had strong binding affinity to both HLA-I and II molecules, respectively. In vivo, administration of vaccines devised by tumor-specific circRNA or its encoding peptides in breast cancer or melanoma-bearing mice dramatically enhanced the infiltration of tumor-antigen specific cytotoxic T cells, leading to effective tumor control. Overall, our findings revealed that noncanonical translation of circRNAs can drive efficient anti-tumor immunity, suggesting that vaccination exploiting tumor-specific circRNAs may serve as an appealing immunotherapeutic strategy against malignant tumors. Citation Format: Di Huang, Jianing Chen, Shicheng Su, Erwei Song. Tumor-specific circRNAs elicit anti-tumor immune response via encoding cryptic antigenic peptides [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-24-12.
Abstract PO2-25-02: The microbial metabolite trimethylamine N-oxide promotes antitumor immunity in triple-negative breast cancer
Authors: Hai Wang
Journal: Cancer Research (2024)

Abstract Immunotherapy has achieved limited success in patients with triple-negative breast cancer (TNBC), an aggressive disease with a poor prognosis. Commensal microbiota have been proven to colonize the mammary gland, but whether and how they modulate the tumor microenvironment remains elusive. We performed a multiomics analysis of a cohort of patients with TNBC (n = 360) and found genera under Clostridiales, and the related metabolite trimethylamine N-oxide (TMAO) was more abundant in tumors with an activated immune microenvironment. Patients with higher plasma TMAO achieved better responses to immunotherapy. Mechanistically, TMAO induced pyroptosis in tumor cells by activating the endoplasmic reticulum stress kinase PERK and thus enhanced CD8+ T cell-mediated antitumor immunity in TNBC in vivo. Collectively, our findings offer new insights into microbiota-metabolite-immune crosstalk and indicate that microbial metabolites, such as TMAO or its precursor choline, may represent a novel therapeutic strategy to promote the efficacy of immunotherapy in TNBC. Citation Format: Hai Wang. The microbial metabolite trimethylamine N-oxide promotes antitumor immunity in triple-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-25-02.
Abstract PO2-27-05: Composite biomarkers for the prediction of progression-free survival with CDK4/6 inhibitors in metastatic HR+/HER2- breast cancer
Authors: Agnieszka Witkiewicz, Jianxin Wang, Erik Knudsen, Ellis Levine, Tracey O'Connor
Journal: Cancer Research (2024)

Abstract CDK4/6 inhibitors are widely used in combination with endocrine therapy in the treatment of HR+/HER2- metastatic breast cancer. Generally the CDK4/6 inhibitors lead to a doubling of progression-free survival (PFS) over single agent endocrine therapy. In spite of a known mechanism of action, biomarkers to define the duration of response to CDK4/6 inhibitors with either aromatase inhibitors (AI) or fulvestrant (FUL) remain lacking. A cohort of over 300 patients receiving standard of care CDK4/6 inhibitor combination therapy for metastatic disease were consented for participation (NCT04526587). The duration of PFS in both AI and FUL treated sub-groups were comparable to that observed in randomized clinical trials. In this cohort progesterone receptor-status (HR 0.70, p=0.0123), visceral disease (HR 1.55, p=0.0013), prior endocrine therapy (HR 2.34, p&amp;lt; 0.001), and type of endocrine therapy (HR 2.16, p&amp;lt; 0.001) were associated with duration of PFS. To develop biomarkers, gene expression analyses was performed on 313 tumor samples representing over 200 individual patients. Focusing on the pre-treatment metastatic biopsy, established signatures associated with prognosis in HR+/HER2- breast cancer were employed to determine association with response to combination therapy in the metastatic setting. Proliferation-associated signatures were associated with shorter PFS. For example, an established RB loss signature was associated with PFS in both AI (HR 1.9, p=0.009) and FUL (HR 2.8, p=0.007) treated patients. Clinically employed signatures (e.g. OncotypeDx and Mammaprint) harbored variable associations with outcomes. Random Survival Forest feature selection was applied to individual and combined prognostic signatures. This approach resulted in a potent classifier for progression-free survival (HR 10, p&amp;lt; 1E-20). To enable applicability to different manifestations of disease, significant clinical pathological variables were incorporated into the model so that there was equivalent performance in AI and FUL treated patients for prediction of PFS. This predictive algorithm was also strongly associated with overall survival (HR 4.6, p=2.7E-8). Ongoing studies are evaluating the algorithms prospectively in NCT04526587. Citation Format: Agnieszka Witkiewicz, Jianxin Wang, Erik Knudsen, Ellis Levine, Tracey O'Connor. Composite biomarkers for the prediction of progression-free survival with CDK4/6 inhibitors in metastatic HR+/HER2- breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-27-05.
Abstract PO2-27-06: ANXA9 facilitates the exocrine secretion of S100A4 and promotes pleural metastasis in breast cancer
Authors: Xiqian Zhou, Dengfeng Li, Lin Fang, Junyong Zhao
Journal: Cancer Research (2024)

Abstract Metastasis to distant organs stands as the primary contributor to mortality in cases of breast cancer. While localized breast cancer boasts a 5-year survival rate of roughly 99%, this figure drastically declines to approximately 26% for patients afflicted with distant metastasis. Regrettably, the current therapeutic landscape lacks efficacious and targeted interventions for the treatment of metastatic breast cancer. Our investigation has revealed a significant upregulation of S100A4 in metastatic breast cancer tissues, with notably high expression observed in the malignant pleural effusion of patients in advanced stages of the disease. Upon acceptance of the effective treatment, the expression of S100A4 in malignant pleural effusion decreased, along with a decrease in several cytokines, including IL-6, IL-8, CCL2, and CCL5. The breast cancer cellular models demonstrated that ANXA9 has the ability to regulate the excretion of S100A4 from cells into the surrounding medium. Similarly, the mice model of pleural metastasis indicated that the downregulation of ANXA9 (sh-ANXA9) resulted in decreased levels of S100A4 and cytokines IL-6, IL-8, CCL2, and CCL5 in the mice's hydrothorax. Additionally, our findings suggest that ANXA9 regulates the excretion of S100A4 through phosphorylation of ANXA9. The cellular membrane harbored phosphorylated ANXA9, which exhibited two phosphorylation sites. Upon mutation of these sites, the level of ANXA9 phosphorylation decreased, leading to a reduction in the exocrine release of ANXA9 from cells into the medium. Our research further revealed the significant involvement of ANXA9 in facilitating the progression of breast cancer, thereby suggesting that therapeutic interventions targeting ANXA9 could prove efficacious in treating metastatic breast cancer. This work was supported by Shanghai Sailing Program to Dengfeng Li (No. 20YF1437800), grant from the National Natural Science Foundation of China to Dengfeng li (No. 82103454) and grant from the National Natural Science Foundation of China to Lin Fang (No. 82073204). Citation Format: Xiqian Zhou, Dengfeng Li, Lin Fang, Junyong Zhao. ANXA9 facilitates the exocrine secretion of S100A4 and promotes pleural metastasis in breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-27-06.
Abstract PO2-27-07: The Role of HCMV Infection in Facilitating Brain Metastasis through the Creation of a Suppressive Tumor Microenvironment in Breast Cancer Patients
Authors: Wenjuan Dong, Xin Wang, Kun Han, Akshjot Puri, Amna Irfan, Wei Qian, Liliana Guzman, Roberto Rosato, Jianting Sheng, Hong Zhao, Jenny Chang, Stephen Wong
Journal: Cancer Research (2024)

Abstract Human Cytomegalovirus (HCMV) infection has emerged as a noteworthy factor in breast cancer patients, particularly those experiencing brain metastasis. Despite being prevalent and often asymptomatic, HCMV's contribution to tumor progression remains enigmatic. Notably, a high proportion of breast cancer patients with brain metastasis exhibit HCMV positivity in both primary tumors and metastatic lesions. This study aims to elucidate the influence of HCMV infection on brain metastasis by investigating its impact on the tumor microenvironment. Our findings reveal a distinctive immune suppressive tumor microenvironment in HCMV-positive breast cancer patients. This environment is characterized by impaired NK cell function and an elevated accumulation of TH2 cells. To comprehend the role of HCMV in promoting brain metastasis, we have developed a murine breast tumor model using MCMV, enabling us to mirror the clinical trajectory of tumor progression and metastasis. The integration of a GFP reporter gene into the MCMV genome facilitates the tracking of infected cancer cells. Within this model, we observe a significant increase in brain metastasis coupled with reduced survival rates. Single-cell sequencing analysis uncovers diminished NK cell presence and activation, along with heightened TH2 cell accumulation within the tumor microenvironment—results that parallel the clinical observations in breast cancer patients. GSEA analysis underscores the secretion of inhibitory cytokines by MCMV-infected cancer cells, contrasting with their non-infected counterparts. Collectively, our study reveals that CMV infection contributes to brain metastasis in breast cancer by generating inhibitory cytokines. This hampers the recruitment and proliferation of immune cells within the tumor microenvironment and concurrently impairs the cytotoxic capabilities of NK cells. These insights shed light on the intricate interplay between viral infection and tumor progression, offering potential avenues for therapeutic exploration. Citation Format: Wenjuan Dong, Xin Wang, Kun Han, Akshjot Puri, Amna Irfan, Wei Qian, Liliana Guzman, Roberto Rosato, Jianting Sheng, Hong Zhao, Jenny Chang, Stephen Wong. The Role of HCMV Infection in Facilitating Brain Metastasis through the Creation of a Suppressive Tumor Microenvironment in Breast Cancer Patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-27-07.
Abstract PO4-01-01: Prognostic Impact of Adjuvant Trastuzumab for the Treatment of Localized Stage I Breast Cancer - Single Tertiary Center Experience
Authors: Sasha Sapon-Cousineau, Marie Florescu, Danielle Charpentier, Rami Younan, Erica Patocskai, Saima Hassan, Kerianne Boulva, Jean-Pierre Ayoub
Journal: Cancer Research (2024)

Abstract Prognostic Impact of Adjuvant Trastuzumab for the Treatment of Localized Stage I Breast Cancer – Single Tertiary Center Experience Sasha Sapon-Cousineau, Marie Florescu, Danielle Charpentier, Rami Younan, Erica Patocskai, Saima Hassan, Kerianne Boulva, Jean-Pierre Ayoub Centre hospitalier de l’Université de Montréal, Montréal, Québec, Canada The HER2 oncoprotein is an established therapeutic target, and the combination of adjuvant chemotherapy and targeted anti-HER2 therapy substantially reduces the risk of recurrence and death over chemotherapy alone in high-risk operable breast cancers that overexpress HER2. However, most studies demonstrating the benefits of anti-HER2 treatments have focused on cohorts at high risk of recurrence. Limited data exists for low-risk cancers to justify this treatment. We performed a retrospective study from 263 patients treated at our oncology center at the Centre hospitalier de l’Université de Montréal between 2006 and 2019 for HER2-positive, N0 or N0(i+) and T1mic to T1c breast cancers. A total of 227 patients were included, 149 (57%) with anti-HER2 treatment and 78 (30%) without. Patients had a single site of HER2-overexpressing invasive breast neoplasia with a follow-up of at least 6 months. Primary outcome was overall survival. Secondary outcomes were disease-free survival and the impact of tumoral and demographic factors. Median follow-up period was 6.7 years. Overall survival at 5 years was 97% (CI 94, 100) for the group with anti-HER2 treatment versus 92% (CI 85, 98) for the group without anti-HER2 treatment. The difference in overall survival between the two treatment groups increased with tumor size. Disease-free survival at 5 years was 93% (CI 88, 87) for the group with anti-HER2 treatment versus 82% (CI 74, 92) for the group without anti-HER2 treatment. In subgroup analysis, age and tumor size had a significant impact on the difference in disease-free survival between groups. Our study demonstrates the significant impact of anti-HER2 targeted therapies on overall survival and disease-free survival for patients with small, HER2 positive localized breast cancers. Further benefit is seen in certain subgroups, such as older patients and those with tumors larger than 1.0 cm, and this should be considered when determining appropriate treatment. Citation Format: Sasha Sapon-Cousineau, Marie Florescu, Danielle Charpentier, Rami Younan, Erica Patocskai, Saima Hassan, Kerianne Boulva, Jean-Pierre Ayoub. Prognostic Impact of Adjuvant Trastuzumab for the Treatment of Localized Stage I Breast Cancer - Single Tertiary Center Experience [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-01-01.
Abstract PO3-25-01: CTLA4 expression profiles and their association with clinical outcomes of breast cancer
Authors: Woo Chul Noh, Young Bum Yoo, Kyoung Sik Park, Sang Eun Nam, Seung Hwan Lim
Journal: Cancer Research (2024)

Abstract The cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is involved in the progression of various cancers, but its biological roles in breast cancer (BRCA) remain unclear. Therefore, we performed a systematic multiomic analysis to expound on the prognostic value and underlying mechanism of CTLA4 in BRCA. First, the expression of CTLA4 in pan-cancer was evaluated using the platforms of Oncomine. Afterward, the web-based bioinformatics platforms of GEPIA and UCLAN were used to compare the expression of CTLA4 in breast cancer and normal tissues. Next, we assessed the relationship between CTLA4 mRNA expression and prognosis in breast cancer patients using the PrognoScan Database, Kaplan-Meier Plotter, and R2: Kaplan-Meier Scanner. Additionally, the correlation between CTLA4 expression and immune cell infiltration in breast cancer and functional enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was performed to elucidate the potential biological functions of CTLA4. Finally, we used the STRINGdb and cytoHubba plugin Cytoscape to create a PPI network and identify known and predicted structural essentials for CTLA4 functions and the top five hub genes. CTLA4 was highly expressed in BRCA tumor tissue compared to normal tissue (p&amp;lt; 0.01). The CTLA4 mRNA levels in BRCA based on breast cancer subtypes of luminal, Human epidermal growth factor receptor 2 (HER-2), and Triple-negative breast cancer (TNBC) were considerably higher than in normal tissues (p&amp;lt; 0.001). However, the overexpression of CTLA4 was associated with a better prognosis in BRCA (P&amp;lt; 0.001), and was correlated with clinicopathological characteristics including age, T-stage, estrogen receptors (ER), progesterone receptors (PR), and PAM50 (P&amp;lt; 0.01). The infiltration of multiple immune cells was associated with increased CTLA4 expression in BRCA (P&amp;lt; 0.001). CTLA4 was highly enriched in antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. This study provides suggestive evidence of the prognostic role of CTLA4 in breast cancer, which may be a therapeutic target for breast cancer. Furthermore, CTLA4 may influence breast cancer prognosis through antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. These findings help us understand how CTLA4 plays a role in breast cancer and set the stage for more research. Citation Format: Woo Chul Noh, Young Bum Yoo, Kyoung Sik Park, Sang Eun Nam, Seung Hwan Lim. CTLA4 expression profiles and their association with clinical outcomes of breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-25-01.
Abstract PO3-29-02: Single Nucleotide Polymorphisms (SNPs) in Inflammatory Pathways Associated with Body Mass Index (BMI) and Breast Cancer (BC) Risk: A Scoping Review
Authors: Erina Quinn, Braelyn Wekwerth, Maya Doyle, Ruth Carlos
Journal: Cancer Research (2024)

Abstract Background: BMI is a risk for BC, with inflammation as a possible link. We conducted a scoping review assessing SNPs in inflammatory pathways posited to modify BC risk by BMI. Design: We followed PRISMA guidelines for scoping reviews. Pubmed, Medline and OVID databases were interrogated for publications between 1/2000-12/2023 using search terms “breast cancer” AND [BMI OR “body mass index” OR elevated BMI OR obesity] AND [SNP OR “single nucleotide polymorphism” OR polymorphism OR mutation] AND [inflammation OR cytokines OR IL-1 OR IL-2 OR IL-4 OR IL-6 OR IL-8 OR IL-10 OR IL-12 OR TNF-A or TGFB OR CRP]. A single reviewer assessed 67 unique publications and determined that 17 met inclusion criteria as a case control or cohort study. Two reviewers extracted the following data: demographics, SNP, number of cases and controls by BMI. Disagreements were resolved by consensus with a third reviewer. High BMI was defined by each study using accepted levels within their population: ≥25 (United States, Mexico) or ≥22 (Korea). Unadjusted odds ratios (OR) for BC risk were calculated by SNP stratified by BMI. Results: Data were extractable from 5 studies, all case controls. We requested patient level data for 12 studies from the corresponding author, without response. When stratified by BMI, we detected heterogenous effects of SNPs on BC risk (Table 1, only significant or trending correlations presented). With high BMI, IL-1β-31 TT (OR 2.19, 0.86-5.59) and GC/CC (OR 0.81, 0.68-0.97) correlated with BC risk (p &amp;lt; 0.05). With normal BMI, STAT3 rs1026916 GA (OR 0.78, 0.62-0.96) and JAK2 rs1536800 TT (OR 1.93, 1.07-3.48) correlated with BC risk. Additional SNPs trended to correlate with BC risk (0.05 &amp;lt; mo &amp;gt;≤&amp;lt;/mo &amp;gt;&amp;lt;/math &amp;gt;"&amp;gt;≤ p &amp;lt; mo &amp;gt;≤&amp;lt;/mo &amp;gt;&amp;lt;/math &amp;gt;"&amp;gt;≤ 0.10) by BMI. Conclusion: The association of inflammatory SNPs and BC risk is complex and can be both protective and predisposing to BC risk, with BMI modifying SNP risk. Future research can assess SNPs and BC risk in more diverse populations. Citation Format: Erina Quinn, Braelyn Wekwerth, Maya Doyle, Ruth Carlos. Single Nucleotide Polymorphisms (SNPs) in Inflammatory Pathways Associated with Body Mass Index (BMI) and Breast Cancer (BC) Risk: A Scoping Review [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-29-02.
Abstract PO3-25-06: Expression of CD28, Fas, PD1, and CTLA4 molecules on cellular immune response in the blood peripheral of patients with locally advanced triple-negative breast cancer
Authors: Marcelo Salgado, Fernando Soares, Denise Viana, Amanda Salgado, Carolina Vasconcelos, Carlos Eduardo Anunciação, Eduardo Salgado, Leuridan Torres
Journal: Cancer Research (2024)

Abstract Background: Locally advanced triple-negative breast cancer (TNBC) represents a public health problem in Brazil; its standard treatment consists of neoadjuvant chemotherapy followed by surgical and radiotherapy, with highly variable success rates are depended on access to appropriate cancer treatment, and the type of pathological response. In the last decade, the immune system's role in breast cancer has gained space by demonstrating the favorable impact of lymphocyte tumor infiltrate (TILs) and gene expression of the immune response, especially in tumors with high proliferation rates and negative estrogen receptors. The cellular immune response is regulated by co-stimulatory and co-inhibitory proteins such as CD28, Fas, PD1, and CTLA4 molecules. Methods: This was a longitudinal study with follow-up performed between 2015 and 2017. The study was conducted at the Hospital de Cancer de Pernambuco and Translational Research Laboratory of the Instituto de Medicina Integral Prof. Fernando Figueira (IMIP). Thirty women (18 to 60 years) diagnosed with locally advanced TNBC submitted to neoadjuvant chemotherapy (NAC), and 30 healthy women as a control group were included. The co-stimulatory and co-inhibitory proteins analyses were performed in the peripheral blood of TNBC women before (Pre-NAC) and after NAC (Post-NAC) Results: High levels of CD28+CD3+ T, CD28+CD4+ T, PD1+CD3+ T, and CTLA4+CD3+ T cells in the pathological complete response (pCR) and non-pCR groups compared to the control group (p &amp;lt; 0.05). High levels of Fas+CD4+T cells and PD1+CD8+T cells in the non-pCR compared to the pCR group (p &amp;lt; 0.05). In the paired analysis, significant differences were observed in CD3+T and CD4+T levels with CD28, Fas, and PD1 expression between pre- and post-NAC. Conclusion: Fas+CD4+T and PD1+CD8+T levels in peripheral blood in TNBC are associated with pCR, suggesting potential predictive biomarkers of NAC response. Preliminary results allow us to infer that neoadjuvant chemotherapy modulates the cellular immune response in TNBC women. Citation Format: Marcelo Salgado, Fernando Soares, Denise Viana, Amanda Salgado, Carolina Vasconcelos, Carlos Eduardo Anunciação, Eduardo Salgado, Leuridan Torres. Expression of CD28, Fas, PD1, and CTLA4 molecules on cellular immune response in the blood peripheral of patients with locally advanced triple-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-25-06.