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Impact of concomitant medication on clinical outcomes in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors: A retrospective study.

Thorac Cancer 2021 May 14. Epub 2021 May 14.

Department of Pharmacometrics and Pharmacokinetics, Meiji Pharmaceutical University, Tokyo, Japan.

Background: It has recently been suggested that concomitant medication may affect the clinical outcome of patients treated with immune checkpoint inhibitors (ICIs). However, only a few studies on the impact of concomitant medication on immune-related adverse events (irAEs) have previously been reported. Here, we aimed to determine the impact of concomitant medication on the efficacy and safety of ICIs. Read More

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Avelumab and cetuximab as a therapeutic combination: An overview of scientific rationale and current clinical trials in cancer.

Cancer Treat Rev 2021 Mar 2;97:102172. Epub 2021 Mar 2.

Medical Oncology, Department of Precision Medicine, Università degli Studi della Campania Luigi Vanvitelli, Naples, Italy.

Treatment outcomes have improved with the advent of immune checkpoint inhibitors and small molecule inhibitors. However, many patients do not respond with single agents. Consequently, ongoing research is focused on the use of combination therapies to increase clinical efficacy by potential synergistic effects. Read More

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Meta-analysis of immune-related adverse events in phase 3 clinical trials assessing immune checkpoint inhibitors for lung cancer.

Crit Rev Oncol Hematol 2021 May 11:103351. Epub 2021 May 11.

Medical Oncology, Santa Chiara Hospital, Trento, Italy. Electronic address:

Introduction: The introduction in clinical practice of the immune checkpoint inhibitors (ICIs) radically changed the treatment algorithm of lung cancers. To characterize the toxicity of ICIs (atezolizumab, durvalumab, nivolumab, pembrolizumab) is important for personalizing treatment.

Patients And Methods: We performed a systematic review and meta-analysis of phase III randomized controlled trials assessing ICIs, from inception until April 23rd, 2020. Read More

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The interplay of obesity, gut microbiome and diet in the immune check point inhibitors therapy era.

Semin Cancer Biol 2021 May 11. Epub 2021 May 11.

Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, Goudi, 11527, Athens, Greece. Electronic address:

Immunotherapy has recently emerged as a promising treatment option for many patients, revolutionizing the established therapeutic approach against cancer. Immune checkpoints inhibitors (ICIs) have demonstrated clinical activity in a wide spectrum of malignancies; however, only a minority of patients exhibit durable responses. This response heterogeneity may be partly attributed to host related factors, such as body mass index (BMI), diet and gut microbiome, that have recently emerged as strong influences in ICI responsiveness. Read More

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The evolving role of immune checkpoint inhibitors in the treatment of triple-negative breast cancer.

Clin Adv Hematol Oncol 2021 May;19(5):305-315

Levine Cancer Institute, Atrium Health, Charlotte, North Carolina.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer for which chemotherapy had been the only active treatment option once metastatic disease developed. Immune checkpoint inhibitors (ICIs) are now available to treat patients with advanced TNBC who have programmed cell death ligand 1 (PD-L1)-positive tumors; these agents have been shown to improve clinical outcomes. Additionally, long-term disease control can be achieved in a subset of patients. Read More

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Chimeric antigen receptor T-cell therapy plus checkpoint blockade in thoracic cancers.

Clin Adv Hematol Oncol 2021 May;19(5):295-297

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.

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Automated Identification of Patients With Immune-Related Adverse Events From Clinical Notes Using Word Embedding and Machine Learning.

JCO Clin Cancer Inform 2021 May;5:541-549

Innovation Center for Biomedical Informatics (ICBI), Georgetown University, Washington, DC.

Purpose: Although immune checkpoint inhibitors (ICIs) have substantially improved survival in patients with advanced malignancies, they are associated with a unique spectrum of side effects termed immune-related adverse events (irAEs). To ensure treatment safety, research efforts are needed to comprehensively detect and understand irAEs. Retrospective analysis of data from electronic health records can provide knowledge to characterize these toxicities. Read More

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Human transitional and IgM low mature naïve B cells preserve permissive B cell receptors.

Immunol Cell Biol 2021 May 14. Epub 2021 May 14.

The Garvan Institute for Medical Research, Sydney, NSW, Australia.

The level of IgM displayed on the surface of peripheral blood B cells exhibits a broad dynamic range and has been associated with both development and selection. To determine whether IgM surface expression associates with distinct immunoglobulin heavy chain (IGH) repertoire properties, we performed deep IgM sequencing of peripheral blood transitional and mature naïve B cells in the upper and lower quartiles of surface IgM expression for 12 healthy donors. Mature naïve B cells within the lowest quartile for surface IgM expression displayed more diverse IGH features including increased CDR3 length, IGHJ6 segment usage and aromatic amino acids compared to mature naïve B cells with high surface IgM. Read More

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Tenascin-C immobilizes infiltrating T lymphocytes through CXCL12 promoting breast cancer progression.

EMBO Mol Med 2021 May 14:e13270. Epub 2021 May 14.

The Tumor Microenvironment Laboratory, INSERM UMR_S 1109, Faculté de Médecine, Hopital Civil, Institut d'Hématologie et d'Immunologie, Strasbourg, France.

Immune checkpoint therapy, where CD8 tumor infiltrating T lymphocytes (TIL) are reactivated, is a promising anti-cancer treatment approach, yet with low response rates. The extracellular matrix, in particular tenascin-C, may generate barriers for TIL. To investigate this possibility, we used a MMTV-NeuNT and syngeneic mammary gland grafting model derived thereof with engineered tenascin-C levels and observed accumulation of CD8 TIL in tenascin-C-rich stroma. Read More

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Poly(I:C) enhances the efficacy of phagocytosis checkpoint blockade immunotherapy by inducing IL-6 production.

J Leukoc Biol 2021 May 14. Epub 2021 May 14.

Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.

Macrophage phagocytosis plays essential roles in antitumor immunity. CD47/SIRPα phagocytosis checkpoint blockade has demonstrated therapeutic potential in several hematopoietic cancers, but recent clinical studies reported very limited efficacy against solid malignancies. Here, we show that polyinosinic-polycytidylic acid (Poly(I:C)), a synthetic analog of double-stranded RNA, enhances the antitumor activity of CD47 blockade in colorectal cancer in vitro and in vivo. Read More

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Immunosuppressive Nanoparticles for Management of Immune-Related Adverse Events in Liver.

ACS Nano 2021 May 14. Epub 2021 May 14.

Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, China.

Immune checkpoint blockade (ICB) therapy has been considered as an effective way to boost immune cells to recognize and attack tumors. However, side effects known as immune-related adverse events (irAEs) should be carefully managed. Here, we engineer immunosuppressive nanoparticles by coating PD-L1 overexpressed mesenchymal stem cells (MSCs) plasma membrane on poly lactic--glycolic acid nanoparticles (MSC-PD-L1 NPs) for managing and reducing irAEs induced by immune checkpoint inhibitors. Read More

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TNPO1-Mediated Nuclear Import of FUBP1 Contributes to Tumor Immune Evasion by Increasing NRP1 Expression in Cervical Cancer.

J Immunol Res 2021 24;2021:9994004. Epub 2021 Apr 24.

Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.

Far upstream element binding protein 1 (FUBP1), a DNA-binding protein, participates in diverse tumor-promoting behaviors by regulating the expression of oncogenes in the nucleus, but the underlying mechanisms remain to be elucidated. In the present study, we found that FUBP1 mRNA and protein expressions were markedly upregulated and closely linked with poor prognosis in cervical cancer. , functional experiments showed that knockdown of inhibited CC cell proliferation and migration. Read More

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Autoimmune hepatitis-is histology conclusive?

Ann Transl Med 2021 Apr;9(8):733

Department of Pathology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.

Liver biopsy is an essential and necessary element in the diagnosis and management of autoimmune hepatitis, and is of very special importance in the scoring system for diagnosis. Histopathology shows moderate to severe inflammatory infiltrates with abundant plasma cells in the enlarged portal tracts with interface hepatitis and moderate to severe necroinflammatory lesions in the lobules with lymphoplasmacytic reaction. Regeneration develops with rosette formation and regenerative nodules. Read More

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Mechanism of idiosyncratic drug induced liver injury (DILI): unresolved basic issues.

Ann Transl Med 2021 Apr;9(8):730

Department of Pharmaceutical Sciences, University of Toronto, ON, Canada.

Clinical features of idiosyncratic drug induced liver injury (DILI) are well described in cases that have been assessed for causality using the Roussel Uclaf Causality Assessment Method (RUCAM), but our understanding of the mechanistic steps leading to injury is fragmentary. The difficulties describing mechanistic events can be traced back to the lack of an animal model of experimental idiosyncratic DILI that can mimic the genetic requirements of human idiosyncratic DILI. However, immune tolerance plays a dominant role in the immune response of the liver, and impairment of immune tolerance with immune checkpoint inhibitors increases DILI in both humans and animals. Read More

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Immune checkpoint inhibitors for treatment of small-cell lung cancer: a systematic review and meta-analysis.

Ann Transl Med 2021 Apr;9(8):705

The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

Background: Small cell lung cancer (SCLC) is a very aggressive and proliferative disease, with little progress being having made for its treatment in decades. Our goal was to evaluate the effect of immune checkpoint inhibitors (ICIs) and identify optimal first-line interventions for the treatment of SCLC.

Methods: A systematic literature search of the Cochrane Library, PubMed and oncology conference proceedings were conducted. Read More

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A comprehensive pan-cancer analysis of gene amplification, tumor mutation burden, microsatellite instability, and PD-L1 expression in Chinese cancer patients.

Ann Transl Med 2021 Apr;9(8):677

Department of Oncology, Wuxi People's Hospital, Wuxi, China.

Background: Immune checkpoint inhibitors blocking programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) have emerged as effective treatment options for cancer. However, immunotherapy is only effective in a subset of patients. Identifying effective biomarkers to predict the treatment response to PD-1/PD-L1 inhibitors remains an unmet clinical need. Read More

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Metastasis-associated gene 1 (MTA1) enhances cisplatin resistance of malignant pleural mesothelioma by ATR-Chk1-mediated DNA repair.

Ann Transl Med 2021 Apr;9(8):670

Department of Oncology of the First Affiliated Hospital of Soochow University, Suzhou, China.

Background: Malignant pleural mesothelioma (MPM) chemoresistance remains a challenge to oncologists. In our previous study, we demonstrated that the aberrant expression of metastasis-associated gene 1 () is associated with carcinogenesis and metastasis in MPM. The aim of the present study was to investigate the mechanism of and chemo-resistance in MPM. Read More

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Immune checkpoint inhibitor plus tyrosine kinase inhibitor for unresectable hepatocellular carcinoma in the real world.

Ann Transl Med 2021 Apr;9(8):652

Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China.

Background: This study aimed to evaluate safety and efficacy of programmed death-1 (PD-1) inhibitor sintilimab plus tyrosine kinase inhibitors (TKI) in a real-word cohort of patients with unresectable hepatocellular carcinoma (uHCC).

Methods: A total of 60 patients treated with sintilimab plus TKI between February 2019 and December 2019 were enrolled. Radiological response was recorded by computed tomography (CT) or magnetic resonance imaging (MRI) at baseline and every 6-12 weeks after treatment initiation. Read More

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Comprehensive analysis of tumor microenvironment and identification of an immune signature to predict the prognosis and immunotherapeutic response in lung squamous cell carcinoma.

Ann Transl Med 2021 Apr;9(7):569

Department of Thoracic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Background: Tumor mutation burden (TMB) and immune microenvironment are important determinants of prognosis and immunotherapeutic efficacy for cancer patients. The aim of the present study was to develop an immune signature to effectively predict prognosis and immunotherapeutic response in patients with lung squamous cell carcinoma (LUSC).

Methods: TMB and immune microenvironment characteristics were comprehensively analyzed by multi-omics data in LUSC. Read More

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Reconstruction and Analysis of the Immune-Related LINC00987/A2M Axis in Lung Adenocarcinoma.

Front Mol Biosci 2021 27;8:644557. Epub 2021 Apr 27.

Department of Urology, The First Affiliated Hospital of China Medical University, Shenyang, China.

Enhancer RNAs (eRNAs) participate in tumor growth and immune regulation through complex signaling pathways. However, the immune-related function of the eRNA-mRNA axis in lung adenocarcinoma (LUAD) is unclear. Data on the expression of eRNAs and mRNAs were downloaded from The Cancer Genome Atlas, GEO, and UCSC Xena, including LUAD, and pan-cancer clinical data and mutational information. Read More

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Performance of Different Diagnostic PD-L1 Clones in Head and Neck Squamous Cell Carcinoma.

Front Med (Lausanne) 2021 27;8:640515. Epub 2021 Apr 27.

Institute of Pathology, University of Luebeck and University Hospital Schleswig-Holstein, Luebeck, Germany.

The approval of immune checkpoint inhibitors in combination with specific diagnostic biomarkers presents new challenges to pathologists as tumor tissue needs to be tested for expression of programmed death-ligand 1 (PD-L1) for a variety of indications. As there is currently no requirement to use companion diagnostic assays for PD-L1 testing in Germany different clones are used in daily routine. While the correlation of staining results has been tested in various entities, there is no data for head and neck squamous cell carcinomas (HNSCC) so far. Read More

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Malignant Pleural Effusions-A Window Into Local Anti-Tumor T Cell Immunity?

Front Oncol 2021 27;11:672747. Epub 2021 Apr 27.

National Centre for Asbestos Related Diseases, Institute for Respiratory Health, University of Western Australia, Nedlands, WA, Australia.

The success of immunotherapy that targets inhibitory T cell receptors for the treatment of multiple cancers has seen the anti-tumor immune response re-emerge as a promising biomarker of response to therapy. Longitudinal characterization of T cells in the tumor microenvironment (TME) helps us understand how to promote effective anti-tumor immunity. However, serial analyses at the tumor site are rarely feasible in clinical practice. Read More

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Ipilimumab and Nivolumab-Induced Colitis in a Patient With Recurrent Metastatic Melanoma.

Cureus 2021 Apr 11;13(4):e14414. Epub 2021 Apr 11.

Gastroenterology, Wayne State University, Detroit, USA.

Ipilimumab and nivolumab are immune checkpoint inhibitors that have recently been used in the treatment of metastatic melanoma and other cancers. Immune-mediated colitis is one of their adverse events that need to be differentiated from low-grade diarrhea as one of the most common side effects. A 51-year-old woman with relapsed metastatic melanoma presented with intractable diarrhea, nausea, vomiting, and generalized abdominal pain. Read More

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Triple-negative breast cancer: A run-through of features, classification and current therapies.

Oncol Lett 2021 Jul 5;22(1):512. Epub 2021 May 5.

Department of Biotechnology, Institute of Bioinformatics and Applied Biotechnology, Bengaluru, Karnataka 560100, India.

Breast cancer is the most prevalent cancer in women worldwide. Triple-negative breast cancer (TNBC) is characterized by the lack of expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. It is the most aggressive subtype of breast cancer and accounts for 12-20% of all breast cancer cases. Read More

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An Immune Checkpoint-Related Gene Signature for Predicting Survival of Pediatric Acute Myeloid Leukemia.

J Oncol 2021 19;2021:5550116. Epub 2021 Apr 19.

Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China.

Objective: The aim of this research was to create a new genetic signature of immune checkpoint-associated genes as a prognostic method for pediatric acute myeloid leukemia (AML).

Methods: Transcriptome profiles and clinical follow-up details were obtained in Therapeutically Applicable Research to Generate Effective Treatments (TARGET), a database of pediatric tumors. Secondary data was collected from the Gene Expression Omnibus (GEO) to test the observations. Read More

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Inhibition of checkpoint kinase 1 potentiates anticancer activity of gemcitabine in bladder cancer cells.

Sci Rep 2021 May 13;11(1):10181. Epub 2021 May 13.

Department of Urology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.

Checkpoint kinases (CHKs) are involved in the DNA damage response in many cancer cells. CHK inhibitors have been used in clinical trials in combination with chemotherapeutics; however, their effect against bladder cancer remains unclear. Here, we investigated the efficacy of combining gemcitabine with MK-8776, a novel CHK1 inhibitor, in four bladder cancer cell lines. Read More

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Antigen-driven EGR2 expression is required for exhausted CD8 T cell stability and maintenance.

Nat Commun 2021 May 13;12(1):2782. Epub 2021 May 13.

John Curtin School of Medical Research, Australian National University, ACT, Australia.

Chronic stimulation of CD8 T cells triggers exhaustion, a distinct differentiation state with diminished effector function. Exhausted cells exist in multiple differentiation states, from stem-like progenitors that are the key mediators of the response to checkpoint blockade, through to terminally exhausted cells. Due to its clinical relevance, there is substantial interest in defining the pathways that control differentiation and maintenance of these subsets. Read More

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A cytokine receptor-masked IL2 prodrug selectively activates tumor-infiltrating lymphocytes for potent antitumor therapy.

Nat Commun 2021 May 13;12(1):2768. Epub 2021 May 13.

Department of Immunology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.

As a potent lymphocyte activator, interleukin-2 (IL-2) is an FDA-approved treatment for multiple metastatic cancers. However, its clinical use is limited by short half-life, low potency, and severe in vivo toxicity. Current IL-2 engineering strategies exhibit evidence of peripheral cytotoxicity. Read More

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Pretreatment metastatic growth rate determines clinical outcome of advanced melanoma patients treated with anti-PD-1 antibodies: a multicenter cohort study.

J Immunother Cancer 2021 May;9(5)

Department of Dermatology, University Medical Center Mainz, Mainz, Germany.

Background: Checkpoint inhibitors revolutionized the treatment of metastatic melanoma patients. Although tumor burden and lactate dehydrogenase (LDH) are associated with overall survival (OS), the impact of tumor growth kinetics remains elusive and in part contradictory. The aims of this study were to develop a novel simple and rapid method that estimates pretreatment metastatic growth rate (MGR) and to investigate its prognostic impact in melanoma patients treated with antiprogrammed death receptor-1 (PD-1) antibodies. Read More

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Immune checkpoint inhibitor-induced hypophysitis.

Diagn Interv Imaging 2021 May 10. Epub 2021 May 10.

Université de Paris, Faculté de Médecine, 75006 Paris, France; Department of Radiology, Hôpital Cochin, AP-HP, 75014 Paris, France. Electronic address:

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