Article
Oncology
Ziqing Chen, Le Tong, Shi Yong Neo, Shuijie Li, Jiwei Gao, Susanne Schlisio, Andreas Lundqvist
Summary: Infusion of natural killer (NK) cells is a potential therapy for cancer patients. However, the activity of NK cells is suppressed by regulatory T (Treg) cells within solid tumors. This study investigates the expression of CD25 on NK cells and its association with persistence in Treg cell-containing solid tumor models. The results suggest that CD25(bright) NK cells isolated from IL-15 primed NK cells have increased proliferative and metabolic activity as well as enhanced ability to persist in Treg cell-containing tumor spheroids, supporting strategies to enhance CD25(bright) NK cells for adoptive NK cell therapy.
Article
Oncology
Malgorzata Bajor, Agnieszka Graczyk-Jarzynka, Katsiaryna Marhelava, Anna Burdzinska, Angelika Muchowicz, Agnieszka Goral, Andriy Zhylko, Karolina Soroczynska, Kuba Retecki, Marta Krawczyk, Marta Klopotowska, Zofia Pilch, Leszek Paczek, Karl-Johan Malmberg, Sebastien Walchli, Magdalena Winiarska, Radoslaw Zagozdzon
Summary: This study provides new information on the efficacy of PD-L1-targeted CAR against PD-L1(low) targets. The results show that PD-L1-CAR cells have strong reactivity and cytotoxicity against both PD-L1(high) and PD-L1(low) target cells. Additionally, PD-L1-CAR cells also exhibit potent cytotoxic effects against non-malignant cells.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Immunology
Eunju Shin, Seong Ho Bak, Taeho Park, Jin Woo Kim, Suk-Ran Yoon, Haiyoung Jung, Ji-Yoon Noh
Summary: Gene-engineered immune cell therapies, particularly using CAR-T cells, have significantly impacted cancer treatment. However, there are limitations in targeting a broader range of cancer types. NK cells, a type of innate immune cells, offer a unique biology and can be genetically engineered to serve as a source for immune cell therapies. NK cell-based therapies, including NK cells, CAR-NK cells, and antibodies stimulating NK cell cytotoxicity, have emerged as promising approaches for various cancers. This review provides an overview of NK cell characteristics and discusses diseases that could benefit from NK-based therapies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Xiao Wang, Xuejiao Yang, Yueping Wang, Yunshuo Chen, Ying Yang, Siqi Shang, Wenbo Wang, Yueying Wang
Summary: This study aims to address the challenges of HLA-I downregulation and limited quantity and quality of NK cells in the context of immune evasion. By combining NK cells with tumor-reactive T cells or NY-ESO-1-specific TCR-T cells, tumor lysis can be enhanced, particularly against tumors with downregulated HLA-I expression. This combination strategy has the potential to improve antitumor response and treatment outcomes.
Article
Microbiology
Yongwei Qin, Qinglan Wang, Jiahai Shi
Summary: The down-regulated expression of immune-activating receptors and enhanced expression of immune-inhibitory receptors play a role in chronic infectious diseases and cancer. However, the impact of Mycobacterium tuberculosis infection on the expression of immune checkpoint molecules on natural killer (NK) cells and their functions has been poorly studied. Understanding the function of NK cells during Mtb infection is crucial for a comprehensive understanding of the immune mechanism and evaluation of immunotherapies for treating tuberculosis.
MICROBIOLOGICAL RESEARCH
(2023)
Article
Oncology
Hena Khalique, Richard Baugh, Arthur Dyer, Eleanor M. Scott, Sally Frost, Sarah Larkin, Janet Lei-Rossmann, Leonard W. Seymour
Summary: PD-L1 BiTE is an effective immunotherapeutic approach to kill PD-L1-positive tumor cells and macrophages while leaving T cells unharmed. This approach activates endogenous T cells within malignant ascites, generates a proinflammatory response, and eliminates cells promoting tumor progression. Using an oncolytic virus for local expression of PD-L1 BiTE also prevents 'on-target off-tumor' systemic toxicities and harnesses immunosuppressive protumor conditions to augment immunotherapy in immunologically 'cold' clinical cancers.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Young Eun Lee, Ga-Yeon Go, Eun-Young Koh, Han-Na Yoon, Minkoo Seo, Seung-Mo Hong, Ji Hye Jeong, Jin-Chul Kim, Duck Cho, Tae Sung Kim, Song Cheol Kim, Eunsung Jun, Mihue Jang
Summary: Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) impair the functionality of natural killer (NK) cells, which are considered as a promising therapeutic modality. Targeted therapies against CAFs may enhance NK-mediated cancer killing.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Immunology
Siman Chen, Yukai Liu, Zhiqi Zhong, Chunyan Wei, Yuyin Liu, Xiaoyong Zhu
Summary: Endometriosis is a chronic inflammatory disease affecting 10% of reproductive-age women, characterized by the growth of endometrium-like tissues outside the uterus. Retrograde menstruation and immune factors are believed to contribute to its development. This review highlights the role of the peritoneal immune microenvironment, including immune cells, cytokines, and inflammatory mediators, in the pathogenesis of endometriosis. Dysfunction in the endocrine system further influences the immune microenvironment. Potential diagnostic biomarkers and nonhormonal therapies targeting the immune microenvironment are discussed as alternative treatment options.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Oncology
Farhoodeh Ghaedrahmati, Nafiseh Esmaeil, Maryam Abbaspour
Summary: Natural killer (NK) cells have potential for cancer immunotherapy, but the immunosuppressive tumor microenvironment (TME) hinders their efficacy. Immune checkpoints contribute to NK cell exhaustion and tumor immune escape. Blocking immune checkpoints can rescue exhausted NK cells and enhance their anti-tumor activity. This review focuses on immune checkpoint blockade strategies, particularly using chimeric antigen receptor (CAR)-NK cells, to redirect NK cells to solid tumors.
CANCER COMMUNICATIONS
(2023)
Article
Immunology
Mitch Ganley, Lauren E. Holz, Jordan J. Minnell, Maria N. de Menezes, Olivia K. Burn, Kean Chan Yew Poa, Sarah L. Draper, Kieran English, Susanna T. S. Chan, Regan J. Anderson, Benjamin J. Compton, Andrew J. Marshall, Anton Cozijnsen, Yu Cheng Chua, Zhengyu Ge, Kathryn J. Farrand, John C. Mamum, Calvin Xu, Ian A. Cockburn, Katsuyuki Yui, Patrick Bertolino, Stephanie Gras, Jerome Le Nours, Jamie Rossjohn, Daniel Fernandez-Ruiz, Geoffrey I. McFadden, David F. Ackerley, Gavin F. Painter, Ian F. Hermans, William R. Heath
Summary: Malaria, caused by Plasmodium species transmitted by mosquitoes, can be prevented by inducing liver-resident memory T cells through mRNA vaccines. Addition of an agonist that recruits T cell help improved the efficacy of the vaccine. This strategy shows potential in malaria-endemic regions.
Article
Oncology
Mireia Bachiller, Lorena Perez-Amill, Anthony Matthew Battram, Sebastian Ciro Carne, Amer Najjar, Els Verhoeyen, Manel Juan, Alvaro Urbano-Ispizua, Beatriz Martin-Antonio
Summary: This study demonstrates the important immunoregulatory role of CB-NK collaborating with CAR-T cells to enhance their antitumor activity. Combinatorial treatment based on CAR-T and CAR-NK cells or CB-NK and CAR-T cells showed that CB-NK required high doses for effectiveness, while a low number of CB-NK in the CAR-T product promoted early activation of CAR-T cells and enhanced anti-MM efficacy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Review
Immunology
Markus Bo Schoenberg, Xiaokang Li, Xinyu Li, Yongsheng Han, Nikolaus Borner, Dominik Koch, Markus Otto Guba, Jens Werner, Alexandr Bazhin
Summary: This review summarizes the interactions between major immune effector cells and HCC cells to provide new insights for HCC immunotherapy. The studies indicate that CD8(+) T lymphocytes and NK cells can inhibit HCC cells, but HCC cells can also lead to dysfunction of these effector cells through various mechanisms. Innovative approaches like organoids and direct contact cell co-culture are suggested for investigating the interactions and developing novel immunotherapy strategies.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Oncology
Anil Kumar, Adeleh Taghi Khani, Caroline Duault, Soraya Aramburo, Ashly Sanchez Ortiz, Sung June Lee, Anthony Chan, Tinisha McDonald, Min Huang, Norman J. J. Lacayo, Kathleen M. M. Sakamoto, Jianhua Yu, Christian Hurtz, Martin Carroll, Sarah K. K. Tasian, Lucy Ghoda, Guido Marcucci, Zhaohui Gu, Steven T. T. Rosen, Saro Armenian, Shai Izraeli, Chun-Wei Chen, Michael A. A. Caligiuri, Stephen J. J. Forman, Holden T. T. Maecker, Srividya Swaminathan
Summary: The high expression of IFN-I signaling genes predicts a favorable clinical outcome in B-ALL patients. However, B-ALL microenvironments exhibit intrinsic defects in IFN-I production and immune responses. By using NK cells as therapies, the suppressed IFN-I production in B-ALL can be counteracted.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Immunology
Hui Zhang, Ulrich Costabel, Huaping Dai
Summary: Sarcoidosis is a systemic inflammatory disorder characterized by tissue infiltration with macrophages and lymphocytes, primarily affecting the lungs. Recent research has highlighted the role of different immune cells, including Th17 cells, IFN-gamma-producing Th17 cells, and regulatory T cells, in the pathogenesis of sarcoidosis. Despite advancements in understanding, the specific actions of these cells and the contribution of neglected cells such as B cells, dendritic cells, natural killer cells, and natural killer T cells remain to be fully clarified. Further research is needed to reveal distinct immunological events and potentially develop new therapeutic approaches.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Oncology
Hui Lu, Xiaoyan Zhao, Ziying Li, Yu Hu, Huafang Wang
Summary: The approval of CD19 CAR-engineered T cell products in B-cell malignancies is a breakthrough in CAR-T cell immunotherapy. However, limitations such as GVHD and other adverse effects restrict their wider applications. CAR-NK cells, with their unique characteristics, are considered promising candidates for cellular immunotherapy, offering potential off-the-shelf products for immediate clinical use without HLA-matching restrictions. Researchers are shifting focus from CAR-T cells to CAR-NK cells, discussing their advantages and challenges in clinical applications.
FRONTIERS IN ONCOLOGY
(2021)
Review
Oncology
Marcus Bauer, Simon Jasinski-Bergner, Ofer Mandelboim, Claudia Wickenhauser, Barbara Seliger
Summary: Epstein-Barr virus (EBV), also known as human herpes virus 4, is a pathogenic virus linked to 1-2% of cancers worldwide. It interferes with the immune system and tumor microenvironment through various mechanisms. Understanding these mechanisms can help improve therapies for EBV-related diseases.
Article
Oncology
Simon Jasinski-Bergner, Juliane Bluemke, Marcus Bauer, Saskia Luise Skiebe, Ofer Mandelboim, Claudia Wickenhauser, Barbara Seliger
Summary: This study investigates the relationship between human Epstein-Barr virus (EBV) and various cancers, particularly the role of virus-encoded microRNAs (miRs) in the malignant transformation of infected cells and immune evasion. Through the analysis of experimental data and in vitro experiments, the authors identified genes associated with oncogenic properties, immune escape, and anti-tumoral immune responses, and predicted potential candidate EBV-miRs and their target genes. This integrated method helps to deepen our understanding of the functions of EBV-miRs and their eligibility as markers in different EBV-associated tissues.
Article
Oncology
Karthikeyan Subbarayan, Chiara Massa, Sandra Leisz, Andre Steven, Daniel Bethmann, Katharina Biehl, Claudia Wickenhauser, Barbara Seliger
Summary: The extracellular matrix component biglycan (BGN) is reduced in K-RAS-associated malignancies, leading to altered growth properties, reduced immunogenicity, and worse patients' outcome.
Article
Oncology
Chiara Massa, Barbara Seliger
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Oncology
Miriam Moller, Steffi Turzer, Georgi Ganchev, Andreas Wienke, Wolfgang Schutte, Barbara Seliger, Dagmar Riemann
Summary: The study aimed to identify blood cell parameters correlating with the survival of non-small cell lung cancer patients undergoing immune checkpoint inhibitor therapy combined with chemotherapy. The results suggest that specific blood cell parameters, such as neutrophil-to-lymphocyte ratio, special types of monocytes, and dendritic cell numbers, may serve as predictive biomarkers for cancer patients' survival.
Article
Oncology
Christoforos K. Vaxevanis, Michael Friedrich, Sandy Uta Tretbar, Diana Handke, Yuan Wang, Juliane Bluemke, Reinhard Dummer, Chiara Massa, Barbara Seliger
Summary: This study revealed a novel mechanism in which miRNAs targeting the coding sequence of immune checkpoint genes are functional and have prognostic relevance. It also has the potential for the development of novel miRNA-based therapies.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Barbara Seliger, Simon Jasinski-Bergner, Chiara Massa, Anja Mueller, Katharina Biehl, Bo Yang, Michael Bachmann, Danny Jonigk, Philip Eichhorn, Arndt Hartmann, Claudia Wickenhauser, Marcus Bauer
Summary: The expression of non-classical human leukocyte antigen (HLA)-G is elevated in lung tissues of SARS-CoV-2 infected patients, correlating with immune cell infiltration, altered CD8(+) cell numbers, and changes in lung epithelial cell function.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Medicine, Research & Experimental
Georgiana Toma, Eliza Karapetian, Chiara Massa, Dagmar Quandt, Barbara Seliger
Summary: HDACi treatment increases intracellular protein acetylation level in CD8(+) T cells, but the protein expression profiles are similar between different age groups. CD8(+) T cells from old donors exhibit higher cytokine secretion and activation marker expression compared to those from young donors, which may have clinical relevance.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Oncology
Christoforos K. K. Vaxevanis, Marcus Bauer, Karthikeyan Subbarayan, Michael Friedrich, Chiara Massa, Katharina Biehl, Haifa Kathrin Al-Ali, Claudia Wickenhauser, Barbara Seliger
Summary: The expression of BGN in MDS and sAML is associated with disease progression and inflammation. BGN is expressed in MDS cell lines and patient bone marrow biopsies, and is involved in regulating inflammasome activity. BGN expression is associated with patient survival in MDS and may serve as a biomarker and potential therapeutic target.
Article
Biochemistry & Molecular Biology
Dagmar Riemann, Steffi Turzer, Georgi Ganchev, Wolfgang Schuette, Barbara Seliger, Miriam Moeller
Summary: In this study, small cell lung cancer (SCLC) patients were treated with chemotherapy and immune checkpoint inhibitors, and their blood immune cells were analyzed. The study found that certain blood cell parameters, such as neutrophil/lymphocyte ratio, HLA-DRlow monocytes, and NK cell and dendritic cell numbers, were associated with disease progression and poor overall survival. When comparing SCLC with non-SCLC, SCLC had higher metastases frequency, higher neutrophil/lymphocyte ratio, lower dendritic cell frequencies, and lower NK cell numbers. The study suggests that blood immune cell signature could improve prediction of SCLC patient outcomes and provide insights into the characteristics of this tumor entity.
Article
Oncology
Antonino A. A. Pane, Theresa Kordass, Agnes Hotz-Wagenblatt, Elke Dickes, Annette Kopp-Schneider, Rainer Will, Barbara Seliger, Wolfram Osen, Stefan B. B. Eichmueller
Summary: This study identified several miRNA species that can affect the susceptibility of melanoma cells to T cell-mediated killing. These miRNAs may represent attractive candidates for novel therapy approaches against melanoma and other tumors.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Chiara Massa, Yuan Wang, Nico Marr, Barbara Seliger
Summary: Interferons (IFNs) are secreted proteins that provide important information for understanding the immune system and cytokine signaling pathways. They have diverse physiological and pathophysiological activities, including modulation of host responses, tumor surveillance, and immune responses. However, tumor cells often develop resistance to IFNs, and loss-of-function mutations in IFN signaling components are associated with susceptibility to infectious diseases. This review summarizes the function and clinical relevance of IFNs, particularly their role in tumor immune evasion and pathogen clearance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Helene Schaefer, Karthikeyan Subbarayan, Chiara Massa, Christoforos Vaxevanis, Anja Mueller, Barbara Seliger
Summary: Using bioinformatics analysis, we found that the expression of ECM protein PRELP is reduced in cutaneous melanoma and is associated with decreased patient survival. High PRELP expression is correlated with low expression of MHC class I antigen processing machinery (APM) and interferon (IFN)-γ pathway, as well as increased expression of TFGB1 and TGFBR1. Transfection of PRELP restores MHC class I surface expression and reduces cell proliferation, migration, and invasion in melanoma cells.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Oncology
Miriam Moeller, Wolfgang Schuette, Steffi Turzer, Barbara Seliger, Dagmar Riemann
Summary: This pilot study conducted immune monitoring in advanced non-small cell lung cancer (NSCLC) patients and found that low neutrophil/lymphocyte ratio (NLR), low percentage of suppressive HLA-DRlow monocytes, and clearly detectable numbers of slan+ non-classical monocytes and dendritic cells might be predictive markers for therapy responses and treatment outcomes.
Article
Biochemistry & Molecular Biology
Matthias Bache, Frauke Kadler, Olivia Struck, Daniel Medenwald, Christian Ostheimer, Antje Guettler, Jacqueline Kessler, Matthias Kappler, Anne Riemann, Oliver Thews, Barbara Seliger, Dirk Vordermark
Summary: The concentration of miR-16, miR-29a, and miR-144 in the plasma of NSCLC patients undergoing radiotherapy was evaluated, and their impact on patients' prognosis was assessed. The results showed that the plasma levels of miR-16, miR-29a, and miR-144 had prognostic value in NSCLC patients, while the level of miR-150 did not predict prognosis. Patients with low levels of these three miRs in their plasma at the end of radiotherapy had the worst prognosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)