International Journal Of Cancer Research Articles

Abstract PO2-28-04: Pregnancy-associated relapse of triple-negative breast cancer

Abstract Introduction: Pregnancy Triple-negative breast cancer(TNMC) is the absence of ER PR and HER2 receptor expression. It constitutes about 15-20% of all breast cancers and is known to be the aggressive form with a high relapse rate (1). Interestingly, it usually affects women aged < 40 and has a low survival rate in African-American females. This case is a typical presentation of a 38-year-old young woman with PMH of T2NO right triple-negative breast cancer diagnosed in 2017 s/p right mastectomy with sentinel LN biopsy, received immunotherapy and chemotherapy, has been cancer-free for two years, and developed metastatic cancer during her pregnancy. In this case, we understand the diagnostic and therapeutic challenges of TNBC during pregnancy. Case: A 38-year-old African American woman, G0, T2NO triple negative invasive ductal carcinoma, underwent a right breast mastectomy and sentinel LN biopsy. She received treatment with (Anti-PD-L1 Antibody) concomitant with weekly paclitaxel and Doxorubicin/Cyclophosphamide (AC) chemotherapy. However, she had a residual 4cm tumor for which she was treated with adjuvant therapy with capecitabine for six months. A repeat Mammogram in 2019 showed no evidence of malignancy. In 2021, the patient was G2P2L1, admitted to the hospital after having a seizure. CT reported cystic/necrotic left parietal lesion mass effect with 8mm right-sided midline shift with metastasis to lungs and abdominal wall. She underwent L parietal craniectomy with resection of the tumor. At 32 weeks of gestation , chemotherapy with carboplatin and paclitaxel was given after her C-section and Gamma knife radiosurgery for metastatic lesions. She developed super refractory seizures, was induced into a coma with therapeutically anesthetic agents, and passed eventually. Discussion: Little literature exists on pregnancy-associated relapse of triple-negative breast cancer and its deterioration. Our patient was in remission for two years and was diagnosed with metastatic cancer during her second pregnancy. John et al., (2018) discussed an interesting association between breastfeeding, parity, and occurrence of TNBC, that there is a two-fold increased risk of developing TNBC with high parity(3 full-term pregnancies) and short-term breastfeeding (< 12 months) (2). Studies have also shown that cancers during or postpartum pregnancy are aggressive with more tumor burden and metastasize to the lungs, liver, and brain, which is consistent with our patient. (3) Conclusion: Pregnancy-associated breast cancer is diagnostically and therapeutically challenging during or in the postpartum period and with a high propensity of the triple-negative type. It requires a multidisciplinary team approach, awareness in the African American population, clinical suspicion of breast mass during pregnancy warrants imaging, and prolonged breastfeeding postpartum. Diagnosis is usually delayed due to pregnancy, and more research is needed on the diagnostic modalities during pregnancy for early treatment initiation. References Almansour NM. Triple-Negative Breast Cancer: A Brief Review About Epidemiology, Risk Factors, Signaling Pathways, Treatment and Role of Artificial Intelligence. Front Mol Biosci. 2022 Jan 25;9:836417. doi: 10.3389/fmolb.2022.836417. PMID: 35145999; PMCID: PMC8824427. John EM, Hines LM, Phipps AI, et al. Reproductive history, breast-feeding and risk of triple-negative breast cancer: The Breast Cancer Etiology in Minorities (BEM) study. International Journal of Cancer. 2018;142(11):2273. doi:10.1002/ijc.31258 Amant F, Deckers S, Van Calsteren K, Loibl S, Halaska M, Brepoels L, et al. Breast cancer in pregnancy: recommendations of an international consensus meeting. Eur J Cancer (2010) 46(18):3158–68. 10.1016/j.ejca.2010.09.010 Citation Format: Vaidarshi Abbagoni. Pregnancy-associated relapse of 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 PO2-28-04.

Юрій Дуброва (1955–2023) — біолог з України, якого чув світ: нотатки до біографії

The future famous geneticist Prof. Yuri Dubrova (1955–2023) was born in Kyiv (Ukraine), where he received excellent secondary and higher education and was awarded with a gold medal upon graduating from school. Eventually, he became one of the best graduates of the Department of Vertebrate Zoology at the Faculty of Biology of Taras Shevchenko National University of Kyiv. His interests included theoretical biology, evolutionary theory, genetics, biometrics, and bionics (for some time he studied the lateral lineage of cyprinid fishes). In his last years at the university, he focused on the study of spontaneous mutations. At the Vavilov Institute of General Genetics in Moscow, Y. Dubrova continued his post-graduate studies and successfully defended his PhD thesis. After the collapse of the USSR, he moved to the UK in search of better scientific and technical opportunities, where he became a professor at the University of Leicester. The scientist lived and worked in Leicester until the end of his life. He devoted himself fully to science, especially to radiation, medical and population genetics, and to teaching, and tried to participate in the study of highly complex medical and genetic issues related, in particular, to the consequences of man-made disasters—Chornobyl (Ukraine, Belarus), Semipalatinsk (Kazakhstan)—and other cases of large-scale radiation effects on life. Dr. Dubrova is the author and co-author of more than 150 scientific articles published in leading journals, including the American Journal of Human Genetics, International Journal of Radiation Biology, Radiation Research, Molecular Biology and Evolution, International Journal of Cancer, British Journal of Cancer, Science, and Nature. He co-operated with many of the world’s leading geneticists and gave lectures in Ukraine, Russia, the USA, Canada, Japan, etc. The article uses fragments of the author’s long correspondence with Y. Dubrova, which may be of interest to biographers of F. Dobrzhansky, M. Tymofeiev-Resovsky, O. Sozinov, O. Yablokov, O. Kistiakowsky, as well as to students, teachers, and historians of Kyiv National University, Kaniv Nature Reserve, and the University of Leicester.

Risk factors for oral cancer: Thematic trends and research agenda

Context: Oral cancer is difficult to define due to several factors. It's known as oral squamous cell carcinoma (OSCC) and is common in the head and neck. Geographic variations in the impact of OSCC highlight the need for research on risk factors and treatment trends. Aims: To identify the main research trends of studies on oral cancer risk factors in the scientific literature in the Scopus database and Web of Science. Methods: This was an exploratory study of the risk factors for oral cancer designed considering the eligibility criteria defined by the PRISMA-2020 international statement, that is, inclusion and exclusion. Results: A total of 215 documents from Scopus and Web of Science were subjected to bibliometric analysis. The years 2020 and 2021 were the most productive, with 18 and 22 articles, respectively. The leading author in productivity and impact was Johnson N, the leading journal was Oral Oncology, followed by the International Journal of Cancer, and the main contributing countries were the United States, the United Kingdom and India. The main thematic cluster was composed of concepts such as Tobacco and Alcohol as the major risk factors; concepts such as Mortality or Head and Neck were positioned as emerging within the scientific literature. Conclusions: The main risk factors, i.e., alcohol and tobacco consumption, are relevant in terms of mortality in the consumer population, which is why their role should be determined in future studies.

Abstract 90: Exploring the role of common circulating tumor cell-associated genes in estrogen receptor-positive breast cancer recurrence

Abstract Despite having the best survival among the molecular subtypes, estrogen receptor-positive (ER+) breast cancer has a tendency for late recurrence. Circulating tumor cells (CTCs) are responsible for disease recurrence by seeding tumors at secondary sites. We have previously developed a CTC signature of 90 common regions of gene copy number gain and demonstrated that this signature is significantly more widespread among cells in metastases than primary tumors.1,2 The objective of our current work is to establish whether the expression data from a 133 gene panel largely derived from the CTC signature can be used to assess the risk of recurrence (ROR) in early ER+ breast cancer patients to help guide treatment decisions following surgery. Formalin-fixed, paraffin-embedded (FFPE) ER+ breast tumor biopsies and linked normal (control) tissues from 192 patients are being analyzed with a custom NanoString nCounter probe set of our 133 CTC genes. From data gathered to date, several genes were shown to be significantly overexpressed in tumors compared to reference normal tissues. This includes MMP11, MKI67, LILRB4, UBE2T, BIRC5, CDC6, MYBL2, and NUF2, which had a log2 fold-change of at least 3.5 (n = 34, p < 0.01). The correlation of our CTC genes to ROR is being evaluated by comparison to the results of the Oncotype DX Breast Recurrence Score Test, a well-established clinical test for ROR in ER+ breast cancer, for each patient. So far, it has been shown that the intratumor heterogeneity (ITH) of CTC genes as established by DEPTH2, an ITH algorithm which evaluates mRNA levels, is significantly positively corelated to Oncotype DX score (n = 23, r = 0.41, p = 0.0495). Moving forward, we will create our own ROR scoring system based on gene expression and copy number data from the CTC gene panel and validate it by comparison to Oncotype DX score and other available clinical data for each of the 192 patient samples. The goal of our work is to gain a deeper understanding of the molecular mechanisms that drive metastasis and recurrence in ER+ breast cancer by focusing on CTCs which play a pivotal role in driving these events. 1. Kanwar N, Hu P, Bedard P, Clemons M, McCready D, Done SJ. Identification of genomic signatures in circulating tumor cells from breast cancer. International Journal of Cancer. 2015;137(2):332-344. doi:10.1002/ijc.29399 2. Kanwar N, Balde Z, Nair R, et al. Heterogeneity of Circulating Tumor Cell-Associated Genomic Gains in Breast Cancer and Its Association with the Host Immune Response. Cancer Research. 2021;81(24):6196-6206. doi:10.1158/0008-5472.can-21-1079‌ Citation Format: Martin Rotbauer, Melanie Dawe, Philippe Bedard, David Cescon, Susan Done. Exploring the role of common circulating tumor cell-associated genes in estrogen receptor-positive breast cancer recurrence [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 90.

Global research trend of esophageal squamous cell carcinoma from 2012 to 2022: a bibliometric analysis.

BackgroundEsophageal cancer is currently a worldwide health problem. Esophageal squamous cell carcinoma (ESCC) is the most common pathological type of esophageal cancer, and its treatment methods and therapeutic effects are relatively limited, so it also requires the unremitting efforts of basic and clinical researchers to overcome difficulties. Bibliometric analysis can help sort out global research trends and hotspots, but no bibliometric analysis of ESCC has been reported. Therefore, we performed this study to analyze the global trends and potential hotspots of ESCC to indicate future research directions.MethodsThe articles related to ESCC research were collected from the WoS Core Collection SCI-EXPANDED database from 2012 to 2022. The article information was analyzed by BiblioShiny and VOSviewer. Results were presented as bar and network visualization to describe the current trend of ESCC research. This was a retrospective study evaluating data that is publicly available online and at libraries and institutional review board approval, as such, was not demanded.ResultsThe global publication trend illustrated a strong growth in the ESCC research field (annual growth rate of 11.4%) and the citation trend increased from an average of 2.98 citations per article per year in 2012 to an average of 3.84 citations per article per year in 2019. With the corresponding author’s country, China contributed the largest number (5,063 articles). The scholars from China and USA had the most collaboration (427 times). China had the largest number of institutions conducting ESCC research. Oncotarget, Oncology Letters, and Annals of Surgical Oncology published the most articles, while Cancer Research, International Journal of Cancer, and Journal of Clinical Oncology had the most local citations. Furthermore, the clinical research hotspots involved in the treatment of ESCC and the basic research hotspots involved in tumor malignant phenotype have received the most attention in recent years.ConclusionOur study demonstrated that the research of ESCC has developed rapidly in recent years, and the academic institutions in China have played a decisive role in this field. The global research purpose is to find effective therapies against ESCC, so some emerging hotspots related to ESCC treatment, such as endoscopic therapy, chemoradiotherapy, immunotherapy, tumor microenvironment, and the epithelial-mesenchymal transition will receive more attention and develop rapidly in the future.

(Digital Presentation) Electrochemical Glutamate Sensor Using Copper Oxide Nanomaterials Functionalized with Multiwall Carbon Nanotubes

Glutamate is the most abundant neurotransmitter in the central nervous system (CNS) and plays an important role in different physiological processes. Excess amounts of glutamate cause excitotoxicity resulting in different diseases such as Alzheimer’s and glioma, pain disorders, spinal cord injuries, and cancer1-4. The concentration of glutamate in body fluids such as saliva is associated with those diseases. Therefore, glutamate is a potential biomarker for pathologies. By measuring glutamate levels in biofluids these pathologies can be monitored.Lab-based techniques such as liquid chromatography and gas chromatography offer a low limit of detection, high sensitivity, and precise detection of biomarkers4-7. These techniques are expensive, bulky, time-consuming, and require skilled personnel to operate them and therefore are not suitable for wearable and personalized healthcare applications. In contrast, electrochemical sensors are simple, low-cost, handy, and offer rapid and high sensing performance of biomarkers/analytes8,9.In this work, we fabricated a very simple, low-cost, and reusable enzyme-free electrochemical sensor using copper oxide (CuO) nanomaterials for label-free detection of glutamate. CuO nanomaterials were synthesized by a low-cost wet chemical process. The CuO nanomaterials were dispersed in DI water and the working electrode was prepared by drop casting of CuO dispersion on a screen-printed carbon electrode (SPCE). Multiwall carbon nanotubes (MWCNTs) were used with CuO to enhance the electron transfer from CuO to SPCE (Figure a). Cyclic voltammetry (CV) and linear sweep voltammetry (LSV) were used to perform glutamate sensing in deionized (DI) water at pH 7.4. The peak oxidation current (I pa) is proportional to glutamate (G) presence in DI water (Figure b). The sensor showed good oxidation current event at a low concentration of glutamate (20 µM) in DI water. The normal concentrations of glutamate in body fluids such as plasma and saliva are about 5-100 µM, and 1-30 µM respectively 3. Therefore, CuO nanostructure-based nonenzymatic electrochemical sensor is very potential for low cost, portable, rapid detection of glutamate in those body fluids. We will further discuss details of CuO synthesis, electrode fabrication process, sensing mechanism, and challenges of the glutamate sensor.References Lewerenz and P. Maher, Frontiers in neuroscience. 9 (2015) 469.Takano et al., Nature medicine. 7 (2001) 1010-1015.H Jasim et al., Scientific reports 8.1 (2018): 1-9.Schultz, Z. Uddin, G. Singh, and M. M. Howlader, Analyst. 145 (2020) 321-347.Klimuntowski, M. M. Alam, G. Singh, and M. M. Howlader, ACS Sensor. 5(3) (2020) 620–636.Budczies et al., International journal of cancer. 136 (2015) 1619-1628.Xin et al, Chinese Journal of Analytical Chemistry. 35 (2007), 1151-1154.Hughes et al., Sensors and Actuators B: Chemical. 216 (2015) 614-621.Rocchitta et al., Sensors, 16 (2016) 780.X Zhang et al., The Journal of Physical Chemistry C 112.43 (2008): 16845-16849.Y Li et al., Materials Research Bulletin 43.8-9 (2008): 2380-2385.RP Allaker, and Z Yuan, Nanobiomaterials in clinical dentistry. Elsevier, 2019. 243-275. Figure 1

Cell line authentication: a necessity for reproducible biomedical research.

Immortalized or continuous cell lines are invaluable tools in basic and preclinical research. However, the widespread use of misidentified cell lines is a serious threat to scientific reproducibility. Based on the experiences of mandatory cell line authentication at the International Journal of Cancer (IJC), we provide an overview of the issues pertinent to misidentified cell lines and discuss available solutions. We also summarize the lessons learned, revealing that at least 5% of the human cell lines used in manuscripts considered for peer review are misidentified. About 4% of the considered manuscripts are rejected for severe cell line problems, and most are subsequently published in other journals. In order to diminish such malpractice and its consequences for the scientific record, we postulate that strict multi‐layered quality control is essential. Besides journals and publishers, we encourage scientists, research institutions, and funders to take action on the matter and revise their respective policies. Hence, we provide concrete recommendations on introducing regular authentication schemes and staff training, and discuss future steps for enhancing good cell culture practices.

738 Intratumoral administration of alum-tethered engineered inflammatory cytokines safely elicits potent local and systemic immunity

738 Intratumoral administration of alum-tethered engineered inflammatory cytokines safely elicits potent local and systemic immunity

Factors contributing to time to diagnosis in symptomatic colorectal cancer: A scoping review.

Colorectal cancer (CRC) is the third most common cancer worldwide (Ferlay et al., 2015, International Journal of Cancer, 136, E359), and delayed diagnosis is associated with mortality (Tørring et al., 2011, British Journal of Cancer, 104, 934; Tørring et al., 2012, Journal of Clinical Epidemiology, 65, 669). The purpose of this review was to determine the factors associated with time to diagnosis in symptomatic CRC using scoping review methods. We performed database and citation searches to identify studies which examine the length of any interval from symptom presentation to diagnosis. Study selection was conducted by two independent reviewers. Factors contributing to time to diagnosis were extracted from selected articles and mapped onto a conceptual framework consisting of four levels: patient and disease factors, provider factors, organisation/setting factors and sectors of influence. From the 31 studies included in this review, we identified 138 unique factors, 17 of which were investigated by at least three studies and 11 of which had consistent results. Patient and disease factors were most commonly studied. Patient perception that their symptoms were benign, a non-urgent referral, female sex and rectal tumour location were each associated with a longer time to diagnosis. Thus far, the literature has focused on patient or disease-related factors, while other levels of influence have been relatively understudied.

New study links hair chemicals to breast cancer.

New study links hair chemicals to breast cancer.

Cryo-EM Reveals the Chemo-Mechanical Coupling of the Oncogenic Kinesin-3 KIF14

KIF14 is a member of the kinesin-3 family that is involved in cell division. It localizes to the mitotic spindle during anaphase and to the midbody during cytokinesis. It is considered an oncogene as its overexpression causes proliferation and poor prognosis in breast and other cancers [1]. However, the role of KIF14 during cell division and its molecular action mechanism are still poorly understood. It was shown previously that KIF14 is a slow plus-end-directed motor that can stabilize microtubules in vitro [2]. To understand structurally the chemo-mechanical cycle of this kinesin and its relationship with microtubule stability we compared by cryo-EM constructs of mouse KIF14 in multiple nucleotide states. Three distinct constructs containing the KIF14 motor domain were designed with different lengths on the C-terminal end. The 3D structures of each of the 3 constructs were obtained by cryo-EM in several nucleotide states. The high resolution EM maps obtained reveal nucleotide specific structural changes that are coupled with the neck-linker docking. The structural changes observed correlate with the differences observed in functional assays designed to study microtubule binding and stabilization. Altogether the results provide a near-atomic model of the chemo-mechanical cycle of KIF14 that accounts for its in vitro properties. The structures also resolve general structural features that are key for the function of other motile kinesins. 1. Corson, T.W. and B.L. Gallie, KIF14 mRNA expression is a predictor of grade and outcome in breast cancer. International Journal of Cancer, 2006. 119(5): p. 1088-1094. 2. Arora, K., et al., KIF14 Binds Tightly to Microtubules and Adopts a Rigor-Like Conformation. Journal of Molecular Biology, 2014. 426(17): p. 2997-3015.

ES02.01 Expanding PROs in Daily Practice

ES02.01 Expanding PROs in Daily Practice

Retraction: Investigation of cross-contamination among human cell lines used in China by Mingzhen Wang, Meimei Yang, Yuehong Liu, Yaqing Huang, Fang Ye, Congyi Zheng and Chao Shen.

Increasing attention has been paid to the hazard of cell line cross-contamination. More journals are requiring that cell lines be authenticated prior to manuscript submission. China Center for Type Culture Collection (CCTCC) has authenticated cell lines for publications in the International Journal of Cancer since 2009. Between 2010 and 2016, we authenticated 485 cell lines from 66 Chinese universities and research institutes. Almost 50% of cell lines were misidentified, most were completely replaced by other cell lines (mainly HeLa and its sublines). The number of cell lines we received for authentication increased dramatically after 2013, but the proportion of misidentified cell lines remained elevated (over 50%). We strongly recommend that researchers take authentication of cell lines seriously and routinely perform authentication of the cell lines used in their laboratories. This article is protected by copyright. All rights reserved.

Correlation of Betel Quid with Oral Cancer from 1998 to 2017: A Study Based on Bibliometric Analysis.

Background:Betel quid chewing has been a major risk factor for oral cancer (OC) in southern China. This study aimed to analyze the scientific publications on the relationship between betel quid chewing and OC and construct a model to quantitatively and qualitatively evaluate pertinent publications from 1998 to 2017.Methods:The publications from 1998 to 2017 were retrieved from the Web of Science Core Collection database. Microsoft Excel, Thomson Data Analyzer, VOSviewer, and CiteSpace software were used to analyze the publication outcomes, journals, countries/regions, institutions, authors, research areas, and research frontiers.Results:A total of 788 publications on the relationship between betel quid chewing and OC published until October 25, 2017, were identified. The top 4 related journals were Journal of Oral Pathology Medicine, Oral Oncology, Plos One, and International Journal of Cancer. The top five countries engaged in related research included China, India, the United States, the United Kingdom, and Malaysia. The corresponding disciplines, such as oncology, oral surgery, pathology, environmental and occupational health, and toxicology, were mainly concentrated in three disciplines. The subject terms squamous cell carcinoma, OC, betel quid, expression, oral submucous fibrosis, India, and p53 ranked first among research hotspots. The burst terms squamous cell carcinoma, OC, betel quid, and expression ranked first in research frontiers.Conclusions:Research in this area emphasized hotspots such as squamous cell carcinoma, OC, oral submucosal fibrosis, betel quid, and tobacco. The annual number of publications steadily decreased from 1998 to 2017, with a lack of a systematic study from interdisciplinary perspectives, inadequate pertinent journals, limited regions with the practice of betel quid chewing, and insufficient participation of researchers, which indicate that as the prevalence of OC increases, particularly in China, research in this area warrants further expansion.

Exogenous hormone use and cutaneous melanoma risk in women: The European prospective investigation into cancer and nutrition

This is the peer reviewed version of the following article: Cervenka, I., Al Rahmoun, M., Mahamat-Saleh, Y., Fournier, A., Boutron-Ruault, M.-C., Severi, G. ... Kvaskoff, M. (2019). Exogenous hormone use and cutaneous melanoma risk in women: The European Prospective Investigation into Cancer and Nutrition. International Journal of Cancer, which has been published in final form at https://doi.org/10.1002/ijc.32674. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.

The decellularized extracellular matrix in regenerative medicine.

The decellularized extracellular matrix in regenerative medicine.

The need for a worldwide consensus for cell line authentication: Experience implementing a mandatory requirement at the International Journal of Cancer.

Cell lines are used in life science research worldwide as biological surrogates. All cell lines are subject to major limitations when used as research tools, including (i) cross-contamination with other cells cultured in the same laboratory environment and (ii) evolution in vitro that renders a given cell line inappropriate as a surrogate for a specific biological hypothesis. There is ample evidence that cross-contamination or phenotypic drift of cells in culture can generate irreproducible or misleading data. A small number of scientific journals—the International Journal of Cancer being at the forefront—and funding agencies have recently moved forward to ask for obligatory cell line authentication data. The history of implementing such rules by the International Journal of Cancer exemplifies the difficulties encountered when installing mandatory quality measures in life sciences.

Abstract A30: Modeling an immunotherapy of NK mechanism on a NSCLC patient derived xenograft

Abstract The recent clinical successes of immune checkpoint inhibitors have fueled the intense interest in novel immuno-oncology (I/O) therapeutics. The lack of relevant animal models remains a major hurdle in understanding the mechanism of action and evaluating the efficacy of such therapeutics. Patient derived xenograft (PDX), considered to most closely mimic patient tumors in both histo- and molecular pathology1,2, is however rarely used in I/O studies because it grow only in immune-compromised hosts. In reality, many PDXs grow well in nude mice where certain immune functions remain intact, excluding T-cells/T-cell functions. Therefore, PDX could still potentially be of practical use for studying T-cell independent I/O therapy. This study set out to evaluate a biologics for the treatment of a patient derived xenograft disease, by activating mouse natural killer (NK). NK and CD8 T cells are two major immune effector cell types that mediate cytotoxicity to tumor cells in vivo. One of the immunomodulatory agents, an anti-PD-L1 antibody-based IL-15 immunocytokine, was recently tested as a novel I/O treatment of cancer3. This molecule was engineered to be cross-species for both human and mouse PD-L1 and IL-15 that antagonize PD1/PD-L1 checkpoint-mediated immune suppression and also target the PD-L1-expressing tumor with IL-15 stimulated NK and CD8 T effector cells into local tumor sites, thus synergizing tumor-located anti-tumor immunity. In fact, our previous studies have demonstrated a greatly enhanced anti-tumor activity in the PDL-1-expressing syngeneic mouse tumor models via the mobilization of tumor infiltrating lymphocyte (TILs), over the PD-L1 antibody alone3. Since IL-15 also stimulates NKs in addition to T-cells, we reasoned that this bifunctional agent could also have potential activity against a PD-L1-expressing PDX in nude mice where NK remains functional. LU1901 is previously described NSCLC-PDX1, and was confirmed to express high level of PD-L1 by both RNAseq and flow analysis, after screening of a large panel of PDXs. We implanted LU1901 in Balb/c nude mice, and started to treat the mice by the bifunctional agent when the tumor reached to 150 mm3. Our result clearly demonstrated a significant inhibition of LU1901 growth by the bifunctional agent in nude mice, in the apparent absence of T-cells. When the treated tumors were examined at the termination, significantly infiltrate NK cells were found inside the treated tumors, as measured by both flow cytometry and immunohistochemistry (IHC). The number of infiltrating NK also statistically correlates to the amplitude of the tumor responses. Together, our data suggest that one of important mechanisms of action of this bifunctional agent relies on the tumor-targeting NK activation, and also that PDX could be a useful model suitable for in vivo efficacy analysis of T-cell independent immunotherapy.

Communication and language…: Story of the week

Nursery WorldVol. 2016, No. 15 EYFS ActivitiesCommunication and language…: Story of the weekRebecca WilsonRebecca WilsonSearch for more papers by this authorRebecca WilsonPublished Online:3 Aug 2016https://doi.org/10.12968/nuwa.2016.15.20AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View articleAbstractFrequent repetition of stories can help to develop a child's vocabulary, explains Rebecca Wilson FiguresReferencesRelatedDetailsCited byPrevalence of high‐risk human papillomavirus after HPV ‐vaccination in Denmark29 June 2020 | International Journal of Cancer, Vol. 147, No. 12Journal of General Internal Medicine, Vol. 32, No. 9 25 July 2016Volume 2016Issue 15ISSN (print): 0029-6422ISSN (online): 2059-9358 Metrics History Published online 3 August 2016 Published in print 25 July 2016 Information© MA Education LimitedPDF download

Abstract 548: Characterization of myeloid cells in bladder cancer

Abstract Both cancer-associated inflammation and tumor-mediated immune suppression have been linked with expansion of myeloid cells in multiple tumor types, including bladder [1]. We previously observed a predominance of M2-like macrophages in mouse bladder tumors [2]. However, little is known about the characteristics of these myeloid cells in human bladder cancer. In this study, we analyzed myeloid cells from tumor tissues collected from patients with muscle-invasive bladder cancer. We used flow cytometry to characterize the different subsets of these myeloid cells.Myeloid cells were identified in the bladder tissue. Our results showed that bladder cancer patients have two major CD11b+CD33+ myeloid derived suppressor cell subsets: granulocyte-type HLADR−CD15+ cells and monocyte-type HLADR+CD14+ cells. Analysis of CD45+ CD11b+cells demonstrated that bladder tumors are dominated by phenotypical M2-like (CD163+ CD80lo) CD163+ M2 macrophages. The primary treatment modality for bladder cancer is Bacillus Calmete-Guerin (BCG), a live attenuated mycobacterium that is instilled into the bladder via a urethral catheter [3]. This agent remains one of the most effective immune therapies to date. However, though it is effective in prevention of tumor recurrence, response is heterogeneous and tumor recurrence is observed in up to 50% of patients over time. The predominance of immunosuppressive myeloid cells subsets among TILs in human bladder cancer suggests myeloid cells could be potential targets for therapeutic intervention in bladder cancer. We investigated the role of macrophages in BCG therapy in the MB49 bladder cancer model. Depletion of macrophages by liposomal clodronate (LC) during MB49 tumor challenge resulted in decreased tumor growth compared to BCG monotherapy suggesting that macrophages have a critical role in BCG immunotherapy. This study characterizes these myeloid populations in bladder cancer patients and also investigates their potential role in bladder cancer development and therapeutic response.