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Review
Biochemistry & Molecular Biology
Shuo Wang et al.
Summary: As an emerging sequencing technology, single-cell RNA sequencing (scRNA-Seq) has become a powerful tool for exploring cell heterogeneity and classification. It has been widely used in various research fields including embryology, histology, oncology, and immunology. This review highlights recent technological advancements in scRNA-Seq and discusses its potential applications in traditional Chinese medicine research and disease diagnostics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Virology
Cong Wang et al.
Summary: The study revealed the intra- and intertumoral heterogeneity of epithelial cells in HPV+ cervical adenocarcinoma through single-cell RNA sequencing, providing insights into the gene expression characteristics of different epithelial subclusters. Additionally, the study also identified the differences in tumor epithelial heterogeneity among different patients. This provides important evidence for personalized treatment of patients with HPV+ cervical adenocarcinoma.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Multidisciplinary Sciences
Chao Liu et al.
Summary: By performing single-cell RNA sequencing on human cervical tissues at different stages of malignancy, this study reveals the transcriptional tumorigenic trajectory of cervical epithelial cells in cervical squamous cell carcinoma (CESC) and identifies key factors involved in CESC initiation and progression. It also shows significant correlations between specific myeloid, lymphoid, and endothelial cell populations and CESC progression, as well as their association with patients' prognosis. Furthermore, the study demonstrates the tumor-promoting function of matrix cancer-associated fibroblasts via the NRG1-ERBB3 pathway in CESC. This research provides valuable insights for refining CESC diagnosis and designing optimal treatment strategies.
Review
Oncology
Karin E. de Visser et al.
Summary: Cancers consist of tumor cells and various non-cancerous cells in an altered extracellular matrix, forming complex ecosystems. The tumor microenvironment (TME) includes different immune cell types, cancer-associated fibroblasts, endothelial cells, pericytes, and other tissue-resident cells, all of which play critical roles in cancer pathogenesis. The composition and function of the TME can vary depending on the organ, cancer cell features, tumor stage, and patient characteristics. Understanding the interplay between tumor cell-intrinsic, cell-extrinsic, and systemic factors is crucial for developing effective anti-cancer treatments.
Article
Virology
Chunbo Li et al.
Summary: This study revealed the cellular differences between squamous cell carcinoma (SCC) and adenocarcinoma (AD) in tumor heterogeneity and tumor microenvironment (TME) using single-cell RNA sequencing. SCC exhibited upregulation of epithelial-to-mesenchymal-transition (EMT), hypoxia, and inflammatory response signaling pathways, while AD showed enrichment of cell cycle-related signaling pathways. The study also identified differences in immune cell populations between SCC and AD, providing potential therapeutic strategies for cervical cancer.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Review
Cardiac & Cardiovascular Systems
Emily Trimm et al.
Summary: Vascular endothelial cells play a crucial role in the circulatory system and have been extensively studied in recent years using single-cell genomics and in vivo genetic labelling techniques. These studies have provided new insights into endothelial cell development, plasticity, and heterogeneity, as well as their interactions with other cell types. The findings have important implications for vascular medicine, and the use of advanced techniques like single-cell multimodal omics has further enhanced our understanding of normal vascular physiology and disease perturbations.
NATURE REVIEWS CARDIOLOGY
(2023)
Article
Medicine, General & Internal
Tao Zhang et al.
Summary: This study identified cervical cancer stem cells and revealed the functional changes in cervical stem cells during malignant transformation. The original non-malignant stem cell properties gradually diminished, while the tumor stem cell properties were enhanced. Additionally, stem-like cells in the cervical microenvironment were associated with neoplastic recurrence, and interferon responses were upregulated during lesion progression.
Article
Oncology
Luca Cassetta et al.
Summary: Tumour-associated macrophages (TAMs) play a cancer-promoting role by promoting tumour invasion, metastasis, angiogenesis, and suppressing anti-tumour immune responses. In this Perspective article, the authors explore the evolution of our understanding of TAM biology and enabling technologies in the context of cancer research.
NATURE REVIEWS CANCER
(2023)
Article
Biochemistry & Molecular Biology
Chao Liu et al.
Summary: Radiochemotherapy is an effective treatment for cervical cancer, affecting not only malignant cells but also the immune and stromal compartments of the tumor. Studying the changes in the tumor ecosystem after radiochemotherapy can help improve treatment strategies for cervical cancer.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Review
Immunology
Natalie K. Wolf et al.
Summary: This review explains the role of natural killer (NK) cells in promoting immunity to tumors and discusses various therapeutic approaches being developed for cancer patients. Recent advances have improved our understanding of NK cells in tumor and viral immunity, showcasing their potential for immunotherapy for cancer.
NATURE REVIEWS IMMUNOLOGY
(2023)
Article
Oncology
L. Federico et al.
Summary: This study identified two major TIL immunotypes (IM1 and IM2) in localized NSCLC patients, with IM2 associated with poor prognosis and IM1 associated with good prognosis. The nature of infiltrating T cells, rather than the number, was found to be prognostically relevant and may inform therapeutic approaches for clinical care.
ANNALS OF ONCOLOGY
(2022)
Article
Oncology
Rebecca L. Siegel et al.
Summary: Each year, the American Cancer Society compiles data on cancer occurrence and outcomes in the United States. The latest data shows that breast and prostate cancer progress has stagnated, while lung cancer has shown improvements in survival rates. Lung cancer incidence for advanced disease has declined while localized-stage rates have increased, resulting in higher survival rates. Mortality patterns align with incidence trends, with lung cancer deaths declining rapidly, breast cancer deaths slowing, and prostate cancer deaths stabilizing.
CA-A CANCER JOURNAL FOR CLINICIANS
(2022)
Review
Genetics & Heredity
Niloofar Khairkhah et al.
Summary: This review provides a detailed overview of the current treatment options for HPV-related cervical precancerous and cancerous diseases, including therapeutic vaccines and the use of genome-editing CRISPR/Cas system. Although the development of vaccines has been slow, recent trials have shown promising results.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2022)
Review
Oncology
Xueman Chen et al.
Summary: Cancer cells interact with cellular and non-cellular components in the host internal environment to create a self-sustainable tumor ecosystem. Recent evidence suggests that targeting the vulnerability of this ecosystem could revolutionize cancer therapy. This review comprehensively examines the interaction between cancer cells and the local tumor microenvironment, distant organ niches, immune, nervous and endocrine systems, with a focus on material and energy flow.
CANCER COMMUNICATIONS
(2022)
Review
Oncology
Dragomirka Jovic et al.
Summary: Single-cell RNA sequencing technology is an advanced method for studying the diversity and complexity of RNA transcripts within individual cells, and for understanding the composition and functions of different cell types in highly organized tissues/ organs/ organisms. This technology has made significant contributions to various fields, providing unique insights into health and diseases. It can be used to construct high-resolution atlases of cells in all living organisms, and has the potential to transform current protocols in disease diagnosis and treatment.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Immunology
Chunbo Li et al.
Summary: This study used single-cell sequencing to investigate the molecular mechanism of lymph node metastasis in cervical cancer. The results showed that epithelial cells in metastatic lymph nodes were associated with cell cycle-related and immune response-related signaling pathways, while epithelial cells in primary tumors were enriched in epithelial-mesenchymal transition and oxidative phosphorylation. Additionally, metastatic lymph nodes exhibited an early activated tumor microenvironment with changes in the quantity of T cells and macrophages compared to normal lymph nodes. Cancer-associated fibroblasts in positive lymph nodes were associated with immune regulation, while fibroblasts in tumors underwent epithelial-mesenchymal transition.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Oncology
Qian Sun et al.
Summary: Cervical cancer heterogeneity is crucial for effective prevention and treatment, involving aspects such as immune clearance of viruses, tumorigenesis, metastasis, and drug resistance. The combination of cervical cancer therapeutic vaccine and immune checkpoint inhibitors is an effective strategy to address treatment heterogeneity. Understanding global vaccination rates, screening rates, incidence, and mortality, as well as genomic factors, is important for cervical cancer prevention and control.
BIOMARKER RESEARCH
(2022)
Article
Biology
Chunbo Li et al.
Summary: Single-cell RNA sequencing of cervical cancer has identified four different subtypes of the disease and provided insights into populations of cancer-associated fibroblasts and CD8+ T cell diversity. These findings have implications for precision prognostic and therapeutic stratification of cervical cancer.
COMMUNICATIONS BIOLOGY
(2022)
Letter
Oncology
Chao Liu et al.
CANCER COMMUNICATIONS
(2022)
Article
Virology
Xiaohui Li et al.
Summary: This study characterized the intratumor heterogeneity of HPV-related cervical adenosquamous carcinoma by performing single-cell RNA sequencing. Different epithelial and immune subclusters were identified, each with distinct features and metabolic pathways. The study also found a positive correlation between certain immune cell populations and patient survival.
JOURNAL OF MEDICAL VIROLOGY
(2022)
Article
Chemistry, Multidisciplinary
Zhihua Ou et al.
Summary: This study investigates the immunological microenvironment of cervical squamous cell carcinoma (CSCC) using single-nucleus RNA sequencing and spatial enhanced resolution omics-sequencing techniques. The expression levels of most immune suppressive genes are not significantly higher in the tumor and inflammation areas of CSCC compared to non-cancer samples. Various immune cells are found in different metabolic tumor areas. Additionally, a cluster of pro-tumorigenic cancer-associated myofibroblasts (myCAFs) are identified, which are associated with poor survival probability, immunotherapy resistance, and may be present in a small fraction of advanced cancer patients.
Review
Cell Biology
Jiahui Lei et al.
Summary: Intracellular calcium concentration plays a crucial role in cervical cancer, and modulation of calcium signals can have anti-tumor effects. Recent research advances have shed light on the significance of calcium signals in the occurrence, development, and prognosis of cervical cancer.
Article
Biochemistry & Molecular Biology
Jie Zhang et al.
Summary: This study found that the expression of G alpha i3 is significantly increased in cervical cancer, and it is associated with poor survival in patients. Depletion of G alpha i3 has anti-cervical cancer activity, while overexpression promotes cervical cancer proliferation and migration. The binding of GATA4 to the promoter region of G alpha i3 is enhanced in cervical cancer. The results indicate that G alpha i3 could be a potential therapeutic target for cervical cancer.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Medicine, Research & Experimental
He Huang et al.
Summary: This study explored the safety and feasibility of infusion of autogenous tumor-infiltrating lymphocytes (TILs) following concurrent chemoradiotherapy (CCRT) in patients with locally advanced cervical cancer (CC). The results showed that TIL-based adoptive cell therapy (ACT) may be a potentially effective adjuvant treatment for locally advanced CC patients.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Biochemistry & Molecular Biology
Ruidi Yu et al.
Summary: This study identified that high expression of m6A regulator METTL3 is associated with poor prognosis and HPV status in HPV-related head and neck squamous cell carcinoma and cervical squamous cell carcinoma. METTL3 high expression is negatively correlated with tumor immune cell infiltrations and promotes the expression of immunosuppressive immune checkpoint molecules. The results suggest that METTL3 may serve as a promising therapeutic target for HPV-related cancer.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Review
Oncology
Brandon A. Dyer et al.
Summary: Immunotherapy combined with radiation therapy has shown promising potential in the treatment of gynecologic cancers, particularly for patients with advanced cervical and uterine cancer. Strategies involving immune modulation and multimodality therapy are being explored to enhance treatment outcomes.
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2021)
Review
Oncology
Sizhe Liu et al.
Summary: NK cells, as a specialized immune effector cell type, play a critical role in immune activation against abnormal cells. Unlike T cell activation, NK cell activation is governed by interactions between NK receptors and target cells, leading to significant attention in cancer immunotherapy. Many efforts are focused on developing and engineering NK cell-based cancer immunotherapy.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Review
Oncology
Theo Accogli et al.
Summary: CD4 T lymphocytes play a crucial role in the anti-tumor response, which can be influenced by cytokines present in the microenvironment of tumors. Understanding the impact of tumors and anti-cancer therapies on cytokines and CD4 T lymphocytes is essential in immunotherapy research aiming to enhance the anti-tumor response.
Review
Immunology
Lisette Krabbendam et al.
Summary: ILCs consist of LTi cells, NK cells, ILC1, ILC2, and ILC3, with helper ILCs producing potent cytokines and possessing the ability to switch function and phenotype in response to environmental changes. Recent research indicates the presence of cytotoxic helper ILCs, which can develop from conventional ILCs in humans but require further elucidation in mice.
CURRENT OPINION IN IMMUNOLOGY
(2021)
Review
Immunology
Amit A. Patel et al.
Summary: Phagocytes are a crucial part of the immune cell family, playing a role in tissue maintenance and immune response orchestration. Understanding the kinetic profiles of these cells during inflammation can help in developing rational therapies to boost or reduce their production as needed.
Article
Biochemistry & Molecular Biology
Nisha B. Nagarsheth et al.
Summary: In a first-in-human phase 1 trial, T cells targeting HPV-16 E7 showed promising results in treating metastatic epithelial cancers, with objective clinical responses observed in 6 out of 12 patients. This suggests that genetically engineered T cell therapy may be effective in treating common carcinomas, but further studies are needed to understand the resistance mechanisms in advanced epithelial cancer.
Article
Multidisciplinary Sciences
Liangtao Zheng et al.
Summary: This study constructed a pan-cancer atlas of T cells across 21 cancer types, revealing different composition patterns and state-transition paths of T cells. The correlation between certain T cell populations and patient characteristics sheds light on possible determinants of the tumor microenvironment, providing new insights into T cell immunity and precision immunotherapy.
Review
Dentistry, Oral Surgery & Medicine
Xinmin Li et al.
Summary: The evolution of RNA sequencing technology has enhanced the completeness of genetic information, with bulk RNAseq averaging global gene expression, scRNAseq investigating single-cell RNA biology, and spRNAseq dissecting RNA activities spatially, representing the next generation of RNA sequencing.
INTERNATIONAL JOURNAL OF ORAL SCIENCE
(2021)
Review
Oncology
Louise Ferrall et al.
Summary: Cervical cancer, primarily caused by persistent high-risk HPV infection, remains the fourth most common cancer affecting women worldwide. Current treatments, such as radiotherapy, chemotherapy, and surgical resection, have limited efficacy and significant side effects against advanced disease. Immunotherapy shows promise in reversing immunosuppressive environments and enhancing T-cell functioning to improve treatment success.
CLINICAL CANCER RESEARCH
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Jose Angelo Udal Perucho et al.
Summary: This study examined the associations of IVIM parameters with treatment response in cervical cancer patients following CCRT. It was found that there was a significant correlation between IVIM parameter f and treatment response, with good repeatability. The study concluded that pre-CCRT IVIM parameters could be potential indicators for treatment response in cervical cancer.
EUROPEAN RADIOLOGY
(2021)
Article
Immunology
Takeo Shibata et al.
Summary: The use of high-throughput sequencing has shown that HPV vaccine can induce specific T cell expansion in both peripheral blood and cervical tissue. This approach not only confirms the presence of vaccine-specific T cells in the body, but also provides a novel method to assess vaccine-specific responses in various anatomical areas.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Allergy
Luis Almeida et al.
Summary: The metabolic processes during T-cell development, activation, and function play a crucial role in regulating T-cell fate. Different types of T cells exhibit metabolic preferences and can adapt their nutritional requirements to the tissue environment. The significance of mitochondrial metabolism and the role of key enzymes, accessory pathways, and protein modifications in regulating T-cell function are emphasized in this review.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2021)
Article
Oncology
Susanne K. Kjaer et al.
Summary: The study demonstrates high effectiveness of HPV vaccination against cervical cancer in females vaccinated under the age of 20, while indicating a lack of immediate effect in those vaccinated between 20-30 years old, emphasizing the importance of early age vaccination.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2021)
Review
Oncology
Achraf A. Shamseddine et al.
Summary: HPV modulates the immune microenvironment to create a pro-tumorigenic state of immune suppression. Understanding these mechanisms has led to the development of immunomodulatory treatments showing early clinical promise in patients with HPV-related malignancies.
Review
Oncology
Dorina Belotti et al.
Summary: Tumors rely on blood vessels for growth and metastasis. Different mechanisms of tumor vessel formation have a significant impact on tumor response to therapies, with strategies targeting tumor vasculature showing promise in overcoming drug resistance and improving treatment efficacy.
Review
Oncology
Simona Duranti et al.
Summary: Cervical cancer is a major cause of cancer-related mortality in women globally, and immunotherapy is being investigated as a potential treatment option for advanced, recurrent, or metastatic cervical cancer. HPV infection is the primary cause of almost all cervical cancers, and immunotherapy may enhance treatment outcomes by restoring the immune response against tumors.
Review
Biochemistry & Molecular Biology
Ava J. Boutilier et al.
Summary: The M1/M2 macrophage paradigm is crucial in tumor progression, where M1 macrophages have anti-tumor effects and M2 macrophages contribute to tumor development through various mechanisms. The tumor microenvironment plays a role in influencing macrophage polarization and activation, which is essential for understanding the pro-tumor effects of tumor-associated macrophages.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Yalan Lei et al.
Summary: Single-cell sequencing is a powerful tool that has revolutionized our understanding of the biological characteristics and dynamics within cancer lesions. Its use in cancer research provides valuable information related to malignant cell landscapes, immune cell interactions, tumor heterogeneity, circulating tumor cells, and underlying mechanisms of tumor behaviors, with bright prospects for diagnosis, targeted therapy, and prognostic prediction among various tumors. Advances in single-cell sequencing will undoubtedly enhance our understanding of tumor biological characteristics and uncover potential precise therapeutic targets for patients in the near future.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Review
Oncology
Tong Fu et al.
Summary: Tumors are not only collections of malignant cells, but also organized complex ecosystems. With the emergence of innovative technologies, researchers can more accurately understand the spatial architecture of the tumor immune microenvironment (TIME), improving our knowledge of tumor biology. The spatial architecture of TIME plays a crucial role in tumor biology and is influenced by the gradient of extracellular nonspecific chemicals (ENSCs).
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Editorial Material
Gastroenterology & Hepatology
Jincheng Han et al.
Summary: The application of single-cell RNA sequencing platforms has provided significant insights into the heterogeneity of PDAC, covering both the neoplastic compartment and tumor microenvironment. This Comment discusses key findings from mouse models and human PDAC samples, as well as future opportunities.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2021)
Article
Medicine, General & Internal
N. Colombo et al.
Summary: Adding pembrolizumab to chemotherapy significantly improves progression-free and overall survival in patients with persistent, recurrent, or metastatic cervical cancer when compared to placebo. Anemia and neutropenia are the most common grade 3 to 5 adverse events.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Medicine, Research & Experimental
Chunbo Li et al.
Summary: This study analyzed cells from CC and adjacent normal tissues using single-cell technologies, identifying different subpopulations in tumor cells and revealing the relationship between CSCs and tumor progression. Differences in gene expression between TECs and NECs were compared, and the potential biological function of ECs in vascularization was explored, highlighting the role of marker genes in facilitating connections between cancer cells and ECs.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2021)
Review
Oncology
Guangshun Sun et al.
Summary: Cancer poses a significant threat to human health, necessitating new technologies for further understanding its mechanisms and developing improved detection and treatment strategies. Single-cell RNA sequencing has emerged as an effective method to dissect human tumor tissue, offering new perspectives for research and avenues for explaining cancer biology.
MOLECULAR THERAPY-ONCOLYTICS
(2021)
Review
Immunology
Sterre T. Paijens et al.
Summary: The success of cancer immune checkpoint blockade has led to increased interest in tumor-infiltrating lymphocytes (TILs) across different cancer types. Single-cell analysis has revealed high cellular heterogeneity in TILs, with distinct patterns of immune activation and exhaustion. While TIL distributions are similar across tumor types, their responses to immunotherapy vary, highlighting the complexity of tumor-immune interactions.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Review
Oncology
Christopher J. Pelham et al.
SEMINARS IN CANCER BIOLOGY
(2020)
Review
Oncology
Cedric Zeltz et al.
SEMINARS IN CANCER BIOLOGY
(2020)
Review
Biochemistry & Molecular Biology
Roberta Lugano et al.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2020)
Review
Oncology
I. Kallialay et al.
ANNALS OF ONCOLOGY
(2020)
Review
Oncology
Renjie Wang et al.
Article
Multidisciplinary Sciences
Martin Jinye Zhang et al.
NATURE COMMUNICATIONS
(2020)
Review
Oncology
Andriy Marusyk et al.
Article
Biochemistry & Molecular Biology
Luca Cassetta et al.
Article
Immunology
Jing Ni et al.
Review
Biochemistry & Molecular Biology
Masahiro Kagabu et al.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Oncology
Ludwig Geistlinger et al.
Article
Cell Biology
Junbin Qian et al.
Review
Immunology
Yuanyuan Zhang et al.
CELLULAR & MOLECULAR IMMUNOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Ashley Maynard et al.
Article
Cardiac & Cardiovascular Systems
David T. Paik et al.
Review
Immunology
Gina J. Fiala et al.
IMMUNOLOGICAL REVIEWS
(2020)
Article
Genetics & Heredity
Gabriela S. Kinker et al.
Review
Biochemistry & Molecular Biology
Liqun Yang et al.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2020)
Review
Oncology
Anne M. Van der Leun et al.
NATURE REVIEWS CANCER
(2020)
Review
Immunology
Stefanie K. Wculek et al.
NATURE REVIEWS IMMUNOLOGY
(2020)
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Genetics & Heredity
Xihao Hu et al.
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Oncology
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SEMINARS IN ONCOLOGY NURSING
(2019)
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Rapolas Zilionis et al.
Article
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Mario L. Suva et al.
Review
Medicine, General & Internal
Michael F. Clarke
NEW ENGLAND JOURNAL OF MEDICINE
(2019)
Review
Immunology
Nyambayar Dashtsoodol et al.
FRONTIERS IN IMMUNOLOGY
(2019)
Article
Oncology
Eric Deutsch et al.
Review
Immunology
Lea Monteran et al.
FRONTIERS IN IMMUNOLOGY
(2019)
Article
Oncology
Xiaotao Jiang et al.
Article
Multidisciplinary Sciences
Chao Yang et al.
NATURE COMMUNICATIONS
(2019)
Article
Oncology
Sanja Stevanovic et al.
CLINICAL CANCER RESEARCH
(2019)
Review
Medicine, General & Internal
Paul A. Cohen et al.
Review
Virology
Ian H. Frazer et al.
PAPILLOMAVIRUS RESEARCH
(2019)
Article
Biochemistry & Molecular Biology
Diether Lambrechts et al.
Article
Medicine, Research & Experimental
Xing Qin et al.
Review
Oncology
Sjoerd H. van der Burg et al.
NATURE REVIEWS CANCER
(2016)
Article
Cell Biology
Carl H. June et al.
SCIENCE TRANSLATIONAL MEDICINE
(2015)