EphA2

头颈鳞状细胞癌（HNSCC，head and neck squamous cell carcinoma）是一类影响口腔、鼻腔和咽喉粘膜的癌症，其发生通常与烟草暴露、酗酒和病毒感染有关，目前关于人类乳头瘤状病毒（HPV）感染状态和HNSCC分子特征之间的关联，研究人员并不清楚。近日，一篇发表在国际杂志Journal of Medical Virology上题为“Deciphering head and neck cancer microenvironment: Single‐cell and spatial transcriptomics reveals human papillomavirus‐associated differences”的研究报告中，来自釜山国立大学等机构的科学家们在一项开创性的研究中分析了在HPV感染状态下HNSCC复杂肿瘤微环境中的细胞多样性和分子属性。研究者Kim表示，近些年来HNSCC的发病率大幅上升，但关于HPV感染在HNSCC发病过程中扮演的关键角色及其与HNSCC之间关联背后的具体分子机制，科学家们知之甚少。这项研究中，研究人员利用HPV阴性和HPV阳性患者的样本进行单细胞RNA分析（一种基因测序技术）和空间转录组学分析（ST，spatial transcriptomics，一种先进的分子分析技术），同时还对原发性肿瘤和淋巴结转移性肿瘤（LNMTs）样本进行了相关分析，深入研究的结果或能为揭示HPV感染和HNSCC发生之间的复杂关联提供显著的图像——在HPV阳性的HNSCC情况下，免疫细胞就能积极参与肿瘤的发生，HNSCC的分子特征会受到HPV感染状态的明显影响，而并不是肿瘤的实际位置。图片来源：https://onlinelibrary.wiley.com/doi/10.1002/jmv.29386RNA测序分析和ST分析结果表明，丙酮酸激酶肌（PKM）基因在HPV阴性组织的淋巴结转移性肿瘤的癌症干细胞样群体中发挥着重要的作用，在HPV阴性的HNSCC细胞系中，PKM基因的表达往往是一致的，而且这也揭示了其在球状体结构形成能力中的重要角色，这一点已通过对PKM2基因的遗传敲除来研究，有意思的是，对HPV阳性患者进行ST分析期间，研究人员还证实了诸如此类异位淋巴样结构的存在。于是研究人员想进一步研究，并重点研究关键的血管发生（新血管的形成通路）过程，他们对HPV阴性患者进行单细胞RNA和ST分析，结果发现，Ephrin-A (EPHA2)或许主要参与到了血管发生和细胞迁移通路中。Kim说道，我们关于PKM和EPHA2分子通路的研究发现或许能作为抑制HNSCC癌细胞生长和扩散的治疗性靶点。此外，肿瘤微环境也会受到HPV感染状态的影响，因此研究人员或有望开发出抵御HNSCC的精准医学手段。综上，本文研究增强了科学家们对于人类头颈鳞状细胞癌（HNSCC）微环境的理解，其或有望帮助指导HNSCC疗法的开发，尤其是在抑制癌细胞生长和迁移方面。由此，HPV感染或许会被视为制定疗法策略的一种标准，从而促进科学家们开发针对不同患者的精准个体化治疗策略。参考文献：Hansong Lee, Sohee Park, Ju Hyun Yun, et al. Deciphering head and neck cancer microenvironment: Single‐cell and spatial transcriptomics reveals human papillomavirus‐associated differences, Journal of Medical Virology (2024). DOI:10.1002/jmv.29386本文仅用于学术分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！

CAMBRIDGE, England & BOSTON--(BUSINESS WIRE)-- Bicycle Therapeutics plc (NASDAQ: BCYC), a biopharmaceutical company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle®) technology, today announced the acceptance of three abstracts for poster presentation at the American Association for Cancer Research (AACR) Annual Meeting 2024, taking place in San Diego on April 5-10. Poster Presentation Details: Title: Bicycle Toxin Conjugates® for the treatment of solid tumors Session Title: Cancer Treatment: New Technologies Date and Time: Tuesday, April 9, at 1:30 p.m. PT/4:30 p.m. ET Abstract Number: 5807 Speaker/Lead Author: Stephen Walsh, Ph.D., Bicycle Therapeutics Title: Modulation of the natural killer cell immune response to tumor with a synthetic tumor-immune cell agonist, NK-TICA™ Session Title: CAR-NK, NK Engagers and NK Modulators Date and Time: Monday, April 8, at 9 a.m. PT/12 p.m. ET Abstract Number: 1340 Speaker/Lead Author: Fay Dufort, Ph.D., Bicycle Therapeutics Title: Tumor-targeted activation of CD137 using Bicycles: New insights into mechanism of action and discovery of BT7455, a clinical candidate for the treatment of EphA2-expressing cancers Session Title: Immune Modulation Employing Agonist or Co-Stimulatory Approaches Date and Time: Tuesday, April 9, at 1:30 p.m. PT/4:30 p.m. ET Abstract Number: 5301 Speaker/Lead Author: Johanna Lahdenranta, Ph.D., Bicycle Therapeutics The posters will be made available in the Publications section of bicycletherapeutics.com following the presentations. About Bicycle Therapeutics Bicycle Therapeutics is a clinical-stage biopharmaceutical company developing a novel class of medicines, referred to as Bicycle® molecules, for diseases that are underserved by existing therapeutics. Bicycle molecules are fully synthetic short peptides constrained with small molecule scaffolds to form two loops that stabilize their structural geometry. This constraint facilitates target binding with high affinity and selectivity, making Bicycle molecules attractive candidates for drug development. The company is evaluating BT8009, a Bicycle® Toxin Conjugate (BTC®) targeting Nectin-4, a well-validated tumor antigen; BT5528, a BTC targeting EphA2, a historically undruggable target; and BT7480, a Bicycle Tumor-Targeted Immune Cell Agonist® (Bicycle TICA®) targeting Nectin-4 and agonizing CD137, in company-sponsored clinical trials. Additionally, the company is developing Bicycle® Radio Conjugates (BRC™) for radiopharmaceutical use and, through various partnerships, is exploring the use of Bicycle® technology to develop therapies for diseases beyond oncology. Bicycle Therapeutics is headquartered in Cambridge, UK, with many key functions and members of its leadership team located in Cambridge, Mass. For more information, visit bicycletherapeutics.com. View source version on businesswire.com: Contacts Investors: Stephanie Yao SVP, Investor Relations and Corporate Communications ir@bicycletx.com 857-523-8544 Media: Argot Partners Deborah Elson media@bicycletx.com 212-600-1902 Source: Bicycle Therapeutics plc View this news release online at:

Using RNA sequencing and spatial transcriptomics, the roles of PKM gene and EPHA2 pathway in the development of HNSCC were discovered. BUSAN, South Korea, Feb. 28, 2024 /PRNewswire/ -- Head and neck squamous cell carcinoma (HNSCC) is a type of cancer that affects the mucous membranes of the mouth, nose, and throat. HNSCC is typically associated with tobacco exposure, alcohol abuse, and viral infections. The links between human papillomavirus (HPV) infection status and the molecular characteristics of HNSCC are not clearly defined. Continue Reading The cellular diversity and structural attributes within the tumor microenvironment of HNSCC due to HPV viral infection needs to be ascertained. Using samples from both HPV negative and HPV positive patients for single-cell RNA profiling and spatial transcriptomics, the molecular characteristics of HNSCC were studied. In a novel and pioneering research work, a team of scientists led by Yun Hak Kim, Assistant Professor in the Department of Anatomy and Department of Biomedical Informatics at the School of Medicine at Pusan National University, Korea, has recently studied the cellular diversity and molecular attributes within the complex tumor microenvironment of HNSCC with respect to the status of HPV infection. Their research findings were recently published in the Journal of Medical Virology on 18 January 2024. "The incidence of HNSCC has gone up considerably in the recent years and yet very little is known about the exact molecular mechanisms regarding the role of HPV infection and its link with HNSCC," shares Dr. Kim, revealing the inspiration behind the present research work. Using samples from both HPV negative (HPV−) and HPV positive (HPV+) patients for single-cell RNA profiling, a genetic sequencing technique, and spatial transcriptomics (ST), an advanced molecular profiling technique, the primary tumors and lymph node metastatic tumors (LNMTs) were analyzed. The in-depth research findings provide remarkable imagery into the complex links between HPV infection and the development of HNSCC. In the case of HPV+ HNSCC, immune cells actively participated in the development of tumors. The molecular characteristics of HNSCC were highly influenced by the status of HPV infection rather than the actual location of tumor. The analyses of RNA sequencing and ST indicated the crucial role of pyruvate kinase muscle (PKM) gene in the development of cancer stem cell-like populations in the LNMT of HPV− tissue. In HPV− HNSCC cell lines, the expression of PKM gene was consistent and indicated a role in the spheroid structure formation ability, which was studied using genetic knockdown of PKM2 gene. Interestingly, during the ST analysis of the HPV+ patients, the presence of such ectopic lymphoid structure was confirmed. Dr. Kim and their team went a step further and focused their efforts to study the critical angiogenesis-new blood vessel formation pathway. They used single-cell RNA and ST profiles of HPV− patients and found that Ephrin-A (EPHA2) was mainly involved in angiogenesis and cell migration pathways. "Our novel research findings of PKM and EPHA2 molecular pathways can be utilized as therapeutic targets in suppressing the growth and spread of HNSCC cancer cells. Also, the tumor microenvironment is affected by the status of HPV infection and thus, precision medicine can be developed against HNSCC," concludes Dr. Kim, underlining the potential real-life applications of the research work. Overall, this study significantly enhances our understanding of HNSCC microenvironment. Thus, it can guide new approaches to HNSCC treatment, especially in inhibiting cancer cell growth and migration. Therefore, the HPV infection could be considered a criterion for developing treatment strategies, thereby enabling precision medicine tailored to the patient's condition! Reference Title of original paper: Deciphering Head and Neck Cancer Microenvironment: Single–Cell and Spatial Transcriptomics Reveals Human Papillomavirus–Associated Differences Journal: Journal of Medical Virology DOI: About Pusan National University Website: Contact: Jae-Eun Lee 82 51 510 7928 373618@email4pr.com SOURCE Pusan National University