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An insight on the impact of teleost whole genome duplication on the regulation of the molecular networks controlling skeletal muscle growth.

PLoS One 2021 22;16(7):e0255006. Epub 2021 Jul 22.

Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil.

Fish muscle growth is a complex process regulated by multiple pathways, resulting on the net accumulation of proteins and the activation of myogenic progenitor cells. Around 350-320 million years ago, teleost fish went through a specific whole genome duplication (WGD) that expanded the existent gene repertoire. Duplicated genes can be retained by different molecular mechanisms such as subfunctionalization, neofunctionalization or redundancy, each one with different functional implications. Read More

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Secondary Dysgammaglobulinemia in Children with Hematological Malignancies Treated with Targeted Therapies.

Paediatr Drugs 2021 Jul 22. Epub 2021 Jul 22.

Infectious Disease Research Program, Center for Bone Marrow Transplantation and Department of Pediatric Hematology/Oncology, University Children's Hospital Münster, Münster, Germany.

Targeted therapies have emerged as innovative treatments for patients whose disease does not respond to conventional chemotherapy, and their use has widely expanded in the field of pediatric hematologic malignancies in the last decade. While they carry the promise of improved disease control and survival and are currently investigated in first-line treatment protocols for patients with poor prognostic markers, they are associated with a considerable incidence of specific toxicities, including cytokine-release syndrome, neurotoxicity, hepatotoxicity, nephrotoxicity, cardiotoxicity, endocrine adverse events, and infectious complications. Iatrogenic or secondary dysgammaglobulinemia is a main consequence of targeted therapies using monoclonal antibodies and other antibody-derived treatments that target specific antigens on lymphoid cells (blinatumomab, inotuzumab ozogamicin, rituximab), chimeric antigen receptor T cells, tyrosine kinase inhibitors (imatinib, dasatinib, nilotinib) and, to a lesser extent, checkpoint inhibitors (pembrolizumab, nivolumab). Read More

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Direct Neuronal Reprogramming: Bridging the Gap Between Basic Science and Clinical Application.

Front Cell Dev Biol 2021 5;9:681087. Epub 2021 Jul 5.

Sunnybrook Research Institute, Biological Sciences Platform, Toronto, ON, Canada.

Direct neuronal reprogramming is an innovative new technology that involves the conversion of somatic cells to induced neurons (iNs) without passing through a pluripotent state. The capacity to make new neurons in the brain, which previously was not achievable, has created great excitement in the field as it has opened the door for the potential treatment of incurable neurodegenerative diseases and brain injuries such as stroke. These neurological disorders are associated with frank neuronal loss, and as new neurons are not made in most of the adult brain, treatment options are limited. Read More

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Expansion of CD10 neutrophils and HLA-DR monocytes driving inflammatory responses after myocardial infarction.

Elife 2021 Jul 22;10. Epub 2021 Jul 22.

Department of Cardiology and Angiology, Medical School Hannover, Hannover, Germany.

Immature neutrophils and HLA-DR monocytes expand in cancer, autoimmune diseases and viral infections, but their appearance and immunoregulatory effects on T-cells after acute myocardial infarction (AMI) remain underexplored.

We found an expansion of circulating immature CD16CD66bCD10 neutrophils and CD14HLA-DR monocytes in AMI patients, correlating with cardiac damage, function and levels of immune-inflammation markers. Immature CD10 neutrophils expressed high amounts of MMP-9 and S100A9, and displayed resistance to apoptosis. Read More

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Phosphorylated WNK kinase networks in recoded bacteria recapitulate physiological function.

Cell Rep 2021 Jul;36(3):109416

Department of Cellular & Molecular Physiology, Yale School of Medicine, New Haven, CT 06520, USA; Systems Biology Institute, Yale University, West Haven, CT 06516, USA. Electronic address:

Advances in genetic code expansion have enabled the production of proteins containing site-specific, authentic post-translational modifications. Here, we use a recoded bacterial strain with an expanded genetic code to encode phosphoserine into a human kinase protein. We directly encode phosphoserine into WNK1 (with-no-lysine [K] 1) or WNK4 kinases at multiple, distinct sites, which produced activated, phosphorylated WNK that phosphorylated and activated SPAK/OSR kinases, thereby synthetically activating this human kinase network in recoded bacteria. Read More

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Identification of Human SARS-CoV-2 Monoclonal Antibodies from Convalescent Patients Using EBV Immortalization.

Antibodies (Basel) 2021 Jul 5;10(3). Epub 2021 Jul 5.

Center of Cellular Therapy "G. Lanzani", Division of Hematology, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy.

We report the isolation of two human IgG1k monoclonal antibodies (mAbs) directed against the SARS-CoV-2 spike protein. These mAbs were isolated from two donors who had recovered from COVID-19 infection during the first pandemic peak in the Lombardy region of Italy, the first European and initially most affected region in March 2020. We used the method of EBV immortalization of purified memory B cells and supernatant screening with a spike S1/2 assay for mAb isolation. Read More

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3D Tumor Models for Breast Cancer: Whither We Are and What We Need.

ACS Biomater Sci Eng 2021 Jul 21. Epub 2021 Jul 21.

Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore-560012, India.

Three-dimensional (3D) models have led to a paradigm shift in disease modeling , particularly for cancer. The past decade has seen a phenomenal increase in the development of 3D models for various types of cancers with a focus on studying stemness, invasive behavior, angiogenesis, and chemoresistance of cancer cells, as well as contributions of its stroma, which has expanded our understanding of these processes. Cancer biology is moving into exploring the emerging hallmarks of cancer, such as inflammation, immune evasion, and reprogramming of energy metabolism. Read More

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Current strategies in tailoring methods for engineered exosomes and future avenues in biomedical applications.

J Mater Chem B 2021 Jul 21. Epub 2021 Jul 21.

Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur-208016, UP, India. and Centre for Environmental Science and Engineering, Indian Institute of Technology Kanpur, Kanpur-208016, UP, India and The Mehta Family Centre for Engineering in Medicine, Indian Institute of Technology Kanpur, Kanpur 208016, UP, India and Centre for Nanosciences, Indian Institute of Technology Kanpur, Kanpur-208016, UP, India.

Exosomes are naturally occurring nanovesicles of endosomal origin, responsible for cellular communication. Depending on the cell type, exosomes display disparity in the cargo and are involved in up/down regulation of different biological pathways. Naturally secreted exosomes, owing to their inherent delivery potential, non-immunogenic nature and limited structural resemblance to the cells have emerged as ideal candidates for various drug delivery and therapeutic applications. Read More

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Knockdown of miR-15b partially reverses the cisplatin resistance of NSCLC through the GSK-3β/MCL-1 pathway.

Adv Clin Exp Med 2021 Jul 20. Epub 2021 Jul 20.

Department of Anesthesia, Nanhua University, Hengyang, China.

Background: Induction of acquired drug resistance occurs frequently with cisplatin-based therapy for non-small cell lung cancer (NSCLC). As recent studies have demonstrated that deregulation of microRNAs (miRNAs) is associated with drug resistance in cancers, correcting the deregulation of miRNAs represents a promising strategy to reverse acquired resistance in NSCLC.

Objectives: This study investigated the functional role of miR-15b in cisplatin resistance in NSCLC. Read More

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Isolation of Microvascular Endothelial Cells.

Bio Protoc 2018 Jun 20;8(12):e2886. Epub 2018 Jun 20.

William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, United Kingdom.

The vascular endothelium is essential to normal vascular homeostasis. Its dysfunction participates in various cardiovascular disorders. Murine endothelial cell culture is an important tool for cardiovascular disease research. Read More

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Constrained TCRγδ-associated Syk activity engages PI3K to facilitate thymic development of IL-17A-secreting γδ T cells.

Sci Signal 2021 Jul 20;14(692). Epub 2021 Jul 20.

Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK.

Murine γδ cells, which are T cells that bear the γδ T cell receptor (TCRγδ) and secrete interleukin-17A (IL-17A), are generated in the thymus and are critical for various immune responses. Although strong TCRγδ signals are required for the development of interferon-γ (IFN-γ)-secreting γδ cells (γδ cells), the generation of γδ cells requires weaker TCRγδ signaling. Here, we demonstrated that constrained activation of the kinase Syk downstream of TCRγδ was required for the thymic development of γδ cells. Read More

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Characterization of neoantigen-specific T cells in cancer resistant to immune checkpoint therapies.

Proc Natl Acad Sci U S A 2021 Jul;118(30)

Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109;

Neoantigen-specific T cells are strongly implicated as being critical for effective immune checkpoint blockade treatment (ICB) (e.g., anti-PD-1 and anti-CTLA-4) and are being targeted for vaccination-based therapies. Read More

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Expansion of cytotoxic natural killer cells in multiple myeloma patients using K562 cells expressing OX40 ligand and membrane-bound IL-18 and IL-21.

Cancer Immunol Immunother 2021 Jul 20. Epub 2021 Jul 20.

Research Center for Cancer Immunotherapy, Gwangju, South Korea.

Background: Natural killer (NK) cell-based immunotherapy is a promising treatment approach for multiple myeloma (MM), but obtaining a sufficient number of activated NK cells remains challenging. Here, we report an improved method to generate ex vivo expanded NK (eNK) cells from MM patients based on genetic engineering of K562 cells to express OX40 ligand and membrane-bound (mb) IL-18 and IL-21.

Methods: K562-OX40L-mbIL-18/-21 cells were generated by transducing K562-OX40L cells with a lentiviral vector encoding mbIL-18 and mbIL-21, and these were used as feeder cells to expand NK cells from peripheral blood mononuclear cells of healthy donors (HDs) and MM patients in the presence of IL-2/IL-15. Read More

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Single-cell transcriptome and TCR profiling reveal activated and expanded T cell populations in Parkinson's disease.

Cell Discov 2021 Jul 20;7(1):52. Epub 2021 Jul 20.

School of Life Science and Technology, Harbin Institute of Technology, Harbin, Heilongjiang, China.

Given the chronic inflammatory nature of Parkinson's disease (PD), T cell immunity may be important for disease onset. Here, we performed single-cell transcriptome and TCR sequencing, and conducted integrative analyses to decode composition, function and lineage relationship of T cells in the blood and cerebrospinal fluid of PD. Combined expression and TCR-based lineage tracking, we discovered a large population of CD8 T cells showing continuous progression from central memory to terminal effector T cells in PD patients. Read More

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Exposure to Plasma From Non-alcoholic Fatty Liver Disease Patients Affects Hepatocyte Viability, Generates Mitochondrial Dysfunction, and Modulates Pathways Involved in Fat Accumulation and Inflammation.

Front Med (Lausanne) 2021 2;8:693997. Epub 2021 Jul 2.

AGING Project, Department of Translational Medicine, University East Piedmont, Novara, Italy.

Changes of lipidic storage, oxidative stress and mitochondrial dysfunction may be involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Although the knowledge of intracellular pathways has vastly expanded in recent years, the role and mechanisms of circulating triggering factor(s) are debated. Thus, we tested the hypothesis that factors circulating in the blood of NAFLD patients may influence processes underlying the disease. Read More

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Folate Deficiency Triggers the Abnormal Segregation of a Region With Large Cluster of CG-Rich Trinucleotide Repeats on Human Chromosome 2.

Front Genet 2021 1;12:695124. Epub 2021 Jul 1.

Center for Chromosome Stability and Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.

Folate deficiency is associated with a broad range of human disorders, including anemia, fetal neural tube defects, age-associated dementia and several types of cancer. It is well established that a subgroup of rare fragile sites (RFSs) containing expanded CGG trinucleotide repeat (TNR) sequences display instability when cells are deprived of folate. However, given that folate sensitive RFSs exist in a very small percentage of the population, they are unlikely to be the cause of the widespread health problems associated with folate deficiency. Read More

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Impactful factors and research design in CRISPR-edited stem cell research from top 10 highly cited articles.

Stem Cell Res Ther 2021 Jul 18;12(1):411. Epub 2021 Jul 18.

Trend Research Centre, Asia University, No. 500, Lioufeng Road, 41354, Wufeng, Taichung, Taiwan.

Our objective in this review was to determine (1) impactful research articles about CRISPR-edited stem cells, (2) factors that affected CRISPR method performance in stem cell, and (3) research design related to CRISPR-edited stem cells. Screening research papers of related topic was carried out by using the Science Citation Index Expanded (SCIE) database of the Clarivate Analytics Web of Science Core Collection updated. We screened impactful CRISPR/Cas9-edited stem cells based on total citation until 2020. Read More

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Rapid Prototyping of Multilayer Microphysiological Systems.

ACS Biomater Sci Eng 2021 Jul 3;7(7):2949-2963. Epub 2020 Jun 3.

Department of Chemical Engineering, Northeastern University, 360 Huntington Ave., 313 Snell Engineering, Boston, Massachusetts 02115, United States.

Microfluidic organs-on-chips aim to realize more biorelevant in vitro experiments compared to traditional two-dimensional (2D) static cell culture. Often such devices are fabricated via poly(dimethylsiloxane) (PDMS) soft lithography, which offers benefits (e.g. Read More

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Different neuroinflammatory gene expression profiles in highly active and benign multiple sclerosis.

J Neuroimmunol 2021 Jul 2;358:577650. Epub 2021 Jul 2.

Research Center of Neurology, Moscow, Russia.

In this study, we aimed to explore the expression of genes associated with neuroinflammation in patients with benign and highly active multiple sclerosis (MS) and healthy controls, to define gene signatures associated with MS as well as disease activity and progression. We identified differences in the expression of 89 genes in benign and highly active MS patients and in healthy controls (q < 0.05). Read More

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Francisella tularensis induces Th1 like MAIT cells conferring protection against systemic and local infection.

Nat Commun 2021 07 16;12(1):4355. Epub 2021 Jul 16.

Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.

Mucosal-associated Invariant T (MAIT) cells are recognized for their antibacterial functions. The protective capacity of MAIT cells has been demonstrated in murine models of local infection, including in the lungs. Here we show that during systemic infection of mice with Francisella tularensis live vaccine strain results in evident MAIT cell expansion in the liver, lungs, kidney and spleen and peripheral blood. Read More

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Innovative therapeutic strategy for B-cell malignancies that combines obinutuzumab and cytokine-induced killer cells.

J Immunother Cancer 2021 Jul;9(7)

Department of Surgery, Oncology and Gastroenterology, Immunology and Oncology Section, University of Padua, Padova, Italy

Background: Patients affected by aggressive B-cell malignancies who are resistant to primary or salvage chemoimmunotherapy have an extremely poor prognosis and limited therapeutic options. Promising therapeutic success has been achieved with the infusion of CD19 chimeric antigen receptor-T cells, but several limits still restrain the administration to a limited proportion of patients. This unmet clinical need might be fulfilled by an adoptive immunotherapy approach that combines cytokine-induced killer (CIK) cells and monoclonal antibodies (mAb) to the CD20 antigen. Read More

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Differentiation of natural killer cells from induced pluripotent stem cells under defined, serum- and feeder-free conditions.

Cytotherapy 2021 Jul 13. Epub 2021 Jul 13.

Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, Indiana, USA; Purdue Center for Cancer Research, West Lafayette, Indiana, USA. Electronic address:

Background Aims: Traditionally, natural killer (NK) cells are sourced from the peripheral blood of donors-a laborious and highly donor-specific process. Processes for generating NK cells from induced pluripotent stem cells (iPSCs) have demonstrated that it is possible to successfully generate renewable alloreactive NK cells that are not only functional in vivo but can also be genetically engineered for enhanced function. However, poor standardization and cumbersome differentiation procedures suggest that further improvements in the control of the differentiation process are necessary. Read More

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Optimized cytotoxicity assay for co-suspended effector and target cells.

J Immunol Methods 2021 Jul 13:113100. Epub 2021 Jul 13.

Shanghai Cell Therapy Group Co., LTD, Shanghai 201805, China. Electronic address:

In recent years, adoptive cell therapy of immune effector cells, such as chimeric antigen receptor-T (CAR-T) cells, natural killer (NK) cells, and epitope-specific cytotoxic T lymphocyte (CTL) cells have been employed in clinical trials. In addition, CD19 CAR-T cells have been approved by the FDA for treatment of non-Hodgkin lymphoma and diffuse large B-cell lymphoma. In this context, it is vital to detect cellular cytotoxicity and monitor the quality of ex vivo expanded immune cells before product release and patient infusion. Read More

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Non-terminally exhausted tumor-resident memory HBV-specific T cell responses correlate with relapse-free survival in hepatocellular carcinoma.

Immunity 2021 Jul 10. Epub 2021 Jul 10.

Singapore Immunology Network, A(∗)STAR, 8A Biomedical Grove, Singapore 138648, Singapore; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, Seattle, WA 98109, USA. Electronic address:

Hepatocellular carcinoma (HCC) often develops following chronic hepatitis B virus (HBV) infection and responds poorly to immune checkpoint blockade. Here, we examined the antigen specificities of HCC-infiltrating T cells and their relevance to tumor control. Using highly multiplexed peptide-MHC tetramer staining of unexpanded cells from blood, liver, and tumor tissues from 46 HCC patients, we detected 91 different antigen-specific CD8 T cell populations targeting HBV, neoantigen, tumor-associated, and disease-unrelated antigens. Read More

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Generation of glucocorticoid-resistant SARS-CoV-2 T cells for adoptive cell therapy.

Cell Rep 2021 07 7;36(3):109432. Epub 2021 Jul 7.

Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Adoptive cell therapy with virus-specific T cells has been used successfully to treat life-threatening viral infections, supporting application of this approach to coronavirus disease 2019 (COVID-19). We expand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) T cells from the peripheral blood of COVID-19-recovered donors and non-exposed controls using different culture conditions. We observe that the choice of cytokines modulates the expansion, phenotype, and hierarchy of antigenic recognition by SARS-CoV-2 T cells. Read More

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Case Report: Angiostrongylus cantonesis Myelitis in Thailand.

Am J Trop Med Hyg 2021 Jul 16. Epub 2021 Jul 16.

Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.

A 67-year-old man presented with headache, middle back pain that radiated to both legs, and paresthesia in the right leg for 1 day. He had eaten raw shrimp 1 week previously. Over the next week after admission, he developed urinary retention and weakness in both legs. Read More

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Adenovirus vector vaccination reprograms pulmonary fibroblastic niches to support protective inflating memory CD8 T cells.

Nat Immunol 2021 Jul 15. Epub 2021 Jul 15.

Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.

Pathogens and vaccines that produce persisting antigens can generate expanded pools of effector memory CD8 T cells, described as memory inflation. While properties of inflating memory CD8 T cells have been characterized, the specific cell types and tissue factors responsible for their maintenance remain elusive. Here, we show that clinically applied adenovirus vectors preferentially target fibroblastic stromal cells in cultured human tissues. Read More

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p53 convergently activates Dux/DUX4 in embryonic stem cells and in facioscapulohumeral muscular dystrophy cell models.

Nat Genet 2021 Jul 15. Epub 2021 Jul 15.

Howard Hughes Medical Institute, Department of Oncological Sciences and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.

In mammalian embryos, proper zygotic genome activation (ZGA) underlies totipotent development. Double homeobox (DUX)-family factors participate in ZGA, and mouse Dux is required for forming cultured two-cell (2C)-like cells. Remarkably, in mouse embryonic stem cells, Dux is activated by the tumor suppressor p53, and Dux expression promotes differentiation into expanded-fate cell types. Read More

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Advances in Immunotherapy for Diffuse Large B Cell Lymphoma.

BioDrugs 2021 Jul 15. Epub 2021 Jul 15.

Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, 1500 E. Duarte Road, Duarte, CA, 91010, USA.

Diffuse large B cell lymphoma (DLBCL) is a heterogeneous disease that is normally treated with combination chemotherapy combined with the anti-CD20 monoclonal antibody rituximab. Although about two-thirds of patients are cured with initial chemo-immunotherapy, a sizable minority of patients will have relapsed or refractory (r/r) DLBCL. Standard therapy for r/r DLBCL is salvage chemotherapy followed by autologous stem cell transplantation (ASCT); however, a minority of patients have long-term remission with this approach. Read More

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The Impact of NK Cell-Based Therapeutics for the Treatment of Lung Cancer for Biologics: Targets and Therapy.

Biologics 2021 7;15:265-277. Epub 2021 Jul 7.

Department of Vascular Surgery, Medical University of Vienna, Vienna, Austria.

Lung cancer has a dismal prognosis and novel targeted therapies leave still room for major improvements and better outcomes. Immunotherapy targeting immune checkpoint (IC) proteins, either as single agents or in combination with chemotherapy, is active but responders constitute only approximately 10-15% of non-small cell lung cancer (NSCLC) patients. Other effector immune cells such as CAR-T cells or NK cells may help to overcome the limitations of the IC inhibitor therapies for lung cancer. Read More

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