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Emulating the Role of Neutrophils in Head and Neck Cancer Microenvironment: Prognostic Role and Therapeutic Strategies 模拟中性粒细胞在癌症头颈部微环境中的作用:预后作用和治疗策略
Pub Date : 2023-08-28 DOI: 10.33696/cancerimmunol.5.076
Khushwant Singh, P. K. Gautam
Head and neck squamous cell carcinoma (HNSCC) are a group of cancers that affect various parts of the head and neck, such as the lip, oral cavity, oropharynx, hypopharynx, and nasopharynx. In India, it accounts for approximately 30–40% of all cancers, while in the United States, it represents around 4% of all cancer cases. HNSCC is a significant contributor to cancer-related deaths globally. While smoking is linked to HNSCC, recent research has confirmed the importance of the human papillomavirus (HPV) in its development. Additionally, HNSCC is characterized by immune deficiencies, where the tumor microenvironment alters immune cell activity to facilitate carcinogenesis. However, researchers have identified novel immunotherapeutic targets for HNSCC, mainly by studying the involvement of inflammatory cells such as neutrophils, eosinophils, and macrophages. Unfortunately, patients with recurring malignancy and distant metastases have limited treatment options, with a prognosis of less than one year. Platinum-based chemotherapy, cetuximab, and other conventional therapies are used to treat recurrent and metastatic HNSCC. The pro and anti-tumor roles of neutrophils in cancer and immunotherapy are explored in this study, with a focus on HNSCC. The primary objective is to increase our understanding of HNSCC biology and immunobiology to uncover viable therapeutic options that are both valid and less cytotoxic.
头颈部鳞状细胞癌(HNSCC)是一组影响头颈部各个部位的癌症,如嘴唇、口腔、口咽、下咽和鼻咽。在印度,它约占所有癌症的30-40%,而在美国,它约代表所有癌症病例的4%。HNSCC是全球癌症相关死亡的重要因素。虽然吸烟与HNSCC有关,但最近的研究证实了人乳头瘤病毒(HPV)在其发展中的重要性。此外,HNSCC的特征是免疫缺陷,肿瘤微环境改变免疫细胞活性以促进癌变。然而,研究人员已经确定了HNSCC的新免疫治疗靶点,主要是通过研究中性粒细胞、嗜酸性粒细胞和巨噬细胞等炎症细胞的参与。不幸的是,复发性恶性肿瘤和远处转移的患者治疗选择有限,预后不到一年。铂基化疗、西妥昔单抗和其他常规疗法用于治疗复发性和转移性HNSCC。本研究探讨了中性粒细胞在癌症和免疫治疗中的促肿瘤和抗肿瘤作用,重点是HNSCC。主要目的是增加我们对HNSCC生物学和免疫生物学的理解,以发现有效且细胞毒性较小的可行治疗方案。
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引用次数: 1
Prognostic Factors of Nintedanib-docetaxel in Patients with Previously Treated Non-small-cell Lung Cancer Nintedanib-docetaxel治疗前非小细胞肺癌癌症患者的预后因素
Pub Date : 2023-08-28 DOI: 10.33696/cancerimmunol.5.077
L. Cabezón-Gutiérrez, S. Custodio-Cabello, V. Pacheco-Barcia, Magda Palka-Kotlowska, Catalina Saez-Bertrand, Marta Blasco-Guerrero
Background: In advanced non-small-cell lung cancer (NSCLC), second-line treatment with nintedanib plus docetaxel improves survival compared with docetaxel, especially in patients with adenocarcinoma histology who progressed within 9 months after the start of firstline treatment. It is therefore necessary to identify new biomarkers/prognostic factors that select the patients who benefit from this type of treatment.Patients and Methods: In this single-center retrospective study, we included patients treated NSCLC with nintedanib plus docetaxel in the second/third line and analyzed potential prognostic factors, many of them related to the inflammatory environment; PD-L1 expression levels, Lung Immune Prognostic Index (LIPI), derived neutrophil/lymphocytes ratio (dNLR), etc.Results: Among 16 patients included in this analysis, the overall response rate was 12.5%, median progression-free survival was 2 months (95% CI, 1.22-2.78) and median overall survival was 6 months (95% CI, 2.11-9.89). LDH level is the only variable related to the disease control rate (70% in normal versus 0% in elevated LDH). The variables analyzed with prognostic significance were; no brain metastases (HR 0.33, 95% CI 0.14-0.78; p=0.011), less than 3 metastatic sites (HR 0.33, 95% CI 0.14-0.78; p=0.011), the non-use of antiangiogenic drugs in the first line (HR 0.53, 95% CI: 0.29-0.98; p=0.043), the absence of elevated LDH at the start of treatment (HR 0.55, 95% CI: 0.3-1; p=0.051) and the absence of liver metastases (HR 0.55, 95% CI: 0.29-1; p=0.05).Conclusions: In NSCLC patients with less than three metastatic sites, no brain or liver metastases, normal LDH values and not previously treated with antiangiogenic drugs in the first line showed a better prognosis when treated with second/third line with nintedanib plus docetaxel.
背景:在晚期非小细胞肺癌癌症(NSCLC)中,与多西他赛相比,nintedanib联合多西他塞尔的二线治疗提高了生存率,尤其是在开始一线治疗后9个月内进展的腺癌组织学患者。因此,有必要确定新的生物标志物/预后因素,以选择从这种类型的治疗中受益的患者。患者和方法:在这项单中心回顾性研究中,我们纳入了第二/第三线使用宁替达尼联合多西他赛治疗NSCLC的患者,并分析了潜在的预后因素,其中许多因素与炎症环境有关;PD-L1表达水平、肺免疫预后指数(LIPI)、衍生中性粒细胞/淋巴细胞比率(dNLR)等。结果:在纳入本分析的16例患者中,总有效率为12.5%,中位无进展生存期为2个月(95%CI,1.22-2.78),中位总生存期为6个月(95%可信区间,2.11-9.89)。LDH水平是与疾病控制率相关的唯一变量(正常组为70%,LDH升高组为0%)。具有预后意义的变量分析为:;无脑转移(HR 0.33,95%CI 0.14-0.78;p=0.011),少于3个转移部位(HR 0.33,95%CI 014-0.78;p=0.011),一线未使用抗血管生成药物(HR 0.53,95%CI:0.29-0.98;p=0.043),治疗开始时LDH升高的缺失(HR 0.55,95%CI:0.3-1;p=0.051)和肝转移的缺失(HR0.55,95%CI:0.29-1;p=0.05)。结论:在转移部位少于三个的NSCLC患者中,没有脑或肝转移,LDH值正常且先前未在第一线中用抗血管生成药物治疗的患者在用宁替达尼加多西他赛的第二/第三线治疗时显示出更好的预后。
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引用次数: 0
Epithelial Mesenchymal Transition: The Ultimate Driver of Cancer on Difficult Paths 上皮间充质转移:癌症在艰难道路上的终极驱动力
Pub Date : 2023-07-07 DOI: 10.33696/cancerimmunol.5.075
Devavrat Tripathi, P. Gupta, S. Kulkarni
Metastasis is the perilous aspect of cancer and is responsible for 90% of deaths due to cancer. It represents an enigmatic and complex biological cascade that is poorly understood. The constant development in cancer research and the advent of new principles in metastasis have discovered some of the molecular keystones like epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) of this cascade. Acknowledgment of the communications between cancer cells and their micro-environment enlightens the biology of metastasis and allows us to understand the mechanism of EMT induction and its role in governing invasion, migration, plasticity, colonization, and therapeutic resistance. EMT is the principal reason behind the cancer cells’ complex behavior, tremendous plasticity, survival, and adoption in a constantly changing environment. Thus, EMT is a perfect driver mechanism to execute metastasis and develop resistance against conventional and targeted therapies. Studies have also discovered the role of EMT in CSCs generation and offered us prospects for evolving more effective treatments to target metastasis and improved patient prognosis.Our primary aim in the present review is to summarize the induction and role of EMT in cancer. This review not only discusses the role of EMT in metastasis but also uncovers the role of EMT in survival, metabolism, and CSCs generation. Further, in this review, we also discuss the strategy to target the EMT for the development of new and effective therapeutics for cancer management.
转移是癌症的危险因素,是癌症90%死亡的原因。它代表了一个神秘而复杂的生物级联,人们对此知之甚少。随着癌症研究的不断发展和转移新原理的出现,发现了一些分子关键,如上皮间充质转移(EMT)和癌症干细胞(CSCs)。对癌症细胞及其微环境之间通讯的认识对转移生物学具有启示意义,并使我们能够理解EMT诱导的机制及其在控制侵袭、迁移、可塑性、定植和治疗耐药性中的作用。EMT是癌症细胞在不断变化的环境中表现出复杂行为、巨大可塑性、存活和适应性的主要原因。因此,EMT是执行转移并对传统和靶向治疗产生耐药性的完美驱动机制。研究还发现了EMT在CSCs生成中的作用,并为我们开发更有效的治疗方法以靶向转移和改善患者预后提供了前景。我们在本综述中的主要目的是总结EMT在癌症中的诱导和作用。这篇综述不仅讨论了EMT在转移中的作用,还揭示了EMT对生存、代谢和CSCs生成的作用。此外,在这篇综述中,我们还讨论了针对EMT开发癌症管理新的有效疗法的策略。
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引用次数: 0
Negative Feedback Expansion of Tregs Caused by Endogenous IL-2 Limits the Activity of IL-2-based Therapies 内源性IL-2引起的Tregs负反馈扩张限制了基于IL-2的治疗的活性
Pub Date : 2023-05-23 DOI: 10.33696/cancerimmunol.5.074
I. Amit, Natalie Levitin, Meital Gadrich, May Ben-Mayor, T. Wyant, Reut Barak, Liron Danielpur, Morya Ifrach, Itzhak Meir, Olga Bluvshtein, Yehezkel Sasson, Sharon Fischman, Guy Nimrod, Michael Zhenin, Yair Fastman, J. Vasselli, Aron Knickerbocker, R. Herbst, Yanay Ofran
Stimulating effector T-cells (Teffs) without inducing regulatory T-cells (Tregs) has been the primary goal of IL-2-based therapies for cancer. Recently, modified IL-2 designed for differential T-cell expansion for the treatment of cancer has failed in the clinic. We propose that treatments based on exogenous administrations of modified IL-2 are inherently undermined by a negative feedback loop, caused by IL-2 secreted endogenously from activated effector T-cells. This endogenous IL-2 secretion subsequentially induces Treg expansion and inhibits the immune response that is essential for cancer clearance. Here, we demonstrate that treatments utilizing exogenous modified IL-2 indeed induce Treg expansion. To circumvent this negative feedback, we computationally designed a novel monoclonal humanized antibody (AU-007) that binds human IL-2 with pM affinity at a predefined epitope and completely blocks IL-2 binding to CD25 that is highly expressed on Tregs, without hindering IL-2 binding to CD122/CD132 dimer receptor expressed over effector cells. This epitope-specific, high-affinity antibody controls endogenous IL-2 and prevents it from expanding Tregs while allowing it to expand Teffs. We show that controlling endogenous IL-2 using AU-007 abrogates the negative feedback loop and replaces it with a positive feedback loop that enhances the expansion of NK cells and Teffs, an effect considered favorable for cancer immunotherapy.
刺激效应t细胞(Teffs)而不诱导调节性t细胞(Tregs)一直是基于il -2的癌症治疗的主要目标。最近,为治疗癌症而设计的用于差异t细胞扩增的改良IL-2在临床中失败了。我们提出,基于外源性给药修饰的IL-2的治疗本质上受到由激活的效应t细胞内源性分泌的IL-2引起的负反馈回路的破坏。这种内源性IL-2分泌随后诱导Treg扩增并抑制对癌症清除至关重要的免疫反应。在这里,我们证明使用外源性修饰的IL-2处理确实诱导Treg扩增。为了避免这种负面反馈,我们通过计算设计了一种新的单克隆人源化抗体(AU-007),它将人IL-2与pM亲和力结合在预定义的表位上,完全阻断IL-2与Tregs上高表达的CD25的结合,而不阻碍IL-2与效应细胞上表达的CD122/CD132二聚体受体的结合。这种表位特异性的高亲和力抗体控制内源性IL-2,并阻止其扩增treg,同时允许其扩增Teffs。我们发现,使用AU-007控制内源性IL-2消除了负反馈回路,代之以正反馈回路,增强了NK细胞和Teffs的扩增,这一效应被认为有利于癌症免疫治疗。
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引用次数: 0
Insights from Long Noncoding RNAs into Cancer-immunity Cycle Regulation 长链非编码rna在癌症免疫周期调控中的应用
Pub Date : 2023-05-23 DOI: 10.33696/cancerimmunol.5.073
Yelin Liang, Yuan Zhang, Xirong Tan, Han Qiao, Jun Ma, Yingqin Li, Na Liu
Accumulating evidence from recent research offers new perspectives on the functions of long non-coding RNAs (lncRNAs) in immunooncology. In addition to modulating the aggressiveness of cancer cells, lncRNAs are essential players in regulating various immune cells and stromal cells, playing a role in reshaping the tumor microenvironment and affecting anti-tumor immunity. The insightful discoveries on the role of lncRNAs in immuno-oncological activities indicate the prognostic value of lncRNA markers. Here, we present an overview of the roles of lncRNAs derived from different cell types in the tumor microenvironment, that is, immune cells, tumor cells, and stromal cells, and summarize their functional characterization and mechanisms in immuno-oncological activities. We also discuss the opportunities and challenges of single-cell-based technologies for analyzing the cellular function of immune-related lncRNAs.
近年来越来越多的研究证据为长链非编码rna (lncRNAs)在免疫肿瘤学中的功能提供了新的视角。除了调节癌细胞的侵袭性外,lncrna在调节各种免疫细胞和基质细胞,重塑肿瘤微环境和影响抗肿瘤免疫等方面发挥着重要作用。lncRNA在免疫肿瘤活动中的作用的深刻发现表明lncRNA标记物的预后价值。本文综述了来自不同细胞类型的lncrna在肿瘤微环境(即免疫细胞、肿瘤细胞和基质细胞)中的作用,并总结了它们在免疫肿瘤学活动中的功能特征和机制。我们还讨论了基于单细胞技术分析免疫相关lncrna细胞功能的机遇和挑战。
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引用次数: 0
Role of Liver Navigation in Surgery Planning and the Challenges 肝脏导航在手术计划中的作用和挑战
Pub Date : 2023-01-26 DOI: 10.33696/cancerimmunol.5.070
S. Dakua, Sagnika Dash, Sagarika Pati, J. Abinahed
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引用次数: 0
Early Integration of Palliative Care for Patients Receiving Systemic Immunotherapy for Renal Cell Carcinoma. 为接受全身免疫疗法的肾细胞癌患者及早纳入姑息治疗。
Pub Date : 2023-01-01 DOI: 10.33696/cancerimmunol.5.072
Megan Stout, Akshay Thaper, Vivien Xu, Eric A Singer, Biren Saraiya
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引用次数: 0
Molecular Iodine Misconceptions: A Novel Formulation Approach to Topical Iodine 分子碘的误解:局部碘的新配方方法
Pub Date : 2022-12-22 DOI: 10.33696/cancerimmunol.4.067
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引用次数: 0
A Surprising Benefit of Cysteine Capping for Antibody Drug Conjugates 半胱氨酸封端用于抗体-药物偶联物的惊人益处
Pub Date : 2022-12-22 DOI: 10.33696/cancerimmunol.4.068
Xiaotian Zhong, A. D'Antona, K. Dutta
antibody-Abstract Antibody-drug conjugates (ADCs), combining the best features of monoclonal antibodies and small molecule drugs
抗体摘要抗体-药物偶联物(ADC),结合了单克隆抗体和小分子药物的最佳特性
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引用次数: 0
Higher Frequency and Poor Prognosis with COVID-19 Associated Cytokine Storm among Cancer Patients: Between Two Fires 癌症患者中新冠肺炎相关细胞因子风暴的高频率和低预后:两次火灾之间
Pub Date : 2022-12-22 DOI: 10.33696/cancerimmunol.4.063
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引用次数: 0
期刊
Journal of cancer immunology
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