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Sukeshi Patel Arora, Devalingam Mahalingam
Over the past few years, the role of immunotherapy in colorectal cancer (CRC) has expanded, specifically in subsets of CRC with microsatellite instability (MSI) for which newer agents, such as programmed death-1 (PD-1) inhibitors, are efficacious. While other immunotherapeutic agents are more immature in development, they have the potential to enhance the efficacy of PD-1 inhibitors and play a role in the treatment algorithm for all subsets of CRC patients. In this review, we will discuss immunotherapeutic agents in development in patients with CRC...
February 2018: Journal of Gastrointestinal Oncology
Marjolein W J Wentink, Yvonne M Mueller, Virgil A S H Dalm, Gertjan J Driessen, P Martin van Hagen, Joris M van Montfrans, Mirjam van der Burg, Peter D Katsikis
Pathogenic gain-of-function mutations in the gene encoding phosphoinositide 3-kinase delta (PI3Kδ) cause activated PI3Kδ syndrome (APDS), a disease characterized by humoral immunodeficiency, lymphadenopathy, and an inability to control persistent viral infections including Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections. Understanding the mechanisms leading to impaired immune response is important to optimally treat APDS patients. Immunosenescence of CD8+ T cells was suggested to contribute to APDS pathogenesis...
2018: Frontiers in Immunology
Alessio Cortellini, Melissa Bersanelli, Sebastiano Buti, Elisabetta Gambale, Francesco Atzori, Federica Zoratto, Alessandro Parisi, Davide Brocco, Annagrazia Pireddu, Katia Cannita, Daniela Iacono, Maria R Migliorino, Teresa Gamucci, Michele De Tursi, Tina Sidoni, Maria Tiseo, Maria Michiara, Anselmo Papa, Gesuino Angius, Silverio Tomao, Maria C Fargnoli, Clara Natoli, Corrado Ficorella
AIM: Tumors related to hereditary susceptibility seem to have an immunosensitive phenotype. MATERIALS & METHODS: We conducted a multicenter retrospective study, to investigate if family history of cancer, multiple neoplasms and early onset of cancer could be related to clinical outcomes of anti-PD-1/PD-L1 therapy. Activity and efficacy data of 211 advanced cancer patients (kidney, non-small-cell lung cancer, melanoma, urothelium, colorectal and HeN), treated at seven Italian centers with anti-PD-1/PD-L1 agents, were analyzed...
March 22, 2018: Immunotherapy
M Shao, D H He, Z Cai
No abstract text is available yet for this article.
March 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Chong Sun, Riccardo Mezzadra, Ton N Schumacher
Expression of programmed death-ligand 1 (PD-L1) is frequently observed in human cancers. Binding of PD-L1 to its receptor PD-1 on activated T cells inhibits anti-tumor immunity by counteracting T cell-activating signals. Antibody-based PD-1-PD-L1 inhibitors can induce durable tumor remissions in patients with diverse advanced cancers, and thus expression of PD-L1 on tumor cells and other cells in the tumor microenviroment is of major clinical relevance. Here we review the roles of the PD-1-PD-L1 axis in cancer, focusing on recent findings on the mechanisms that regulate PD-L1 expression at the transcriptional, posttranscriptional, and protein level...
March 20, 2018: Immunity
Hiroshi Uchi
Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer with frequent metastasis and death. MCC has a mortality rate of 30%, making it more lethal than malignant melanoma, and incidence of MCC has increased almost fourfold over the past 20 years in the USA. MCC has long been considered to be an immunogenic cancer because it occurs more frequently in immunosuppressed patients from organ transplant and HIV infection than in those with immunocompetent. Chronic UV light exposure and clonal integration of Merkel cell polyomavirus (MCPyV) are two major causative factors of MCC...
2018: Frontiers in Oncology
Hridesh Banerjee, Lawrence P Kane
T-cell immunoglobulin and mucin domain 3 (Tim-3) is a transmembrane protein that in both mice and humans has been shown to possess various functions in a context-dependent manner. Thus, Tim-3 has been associated with both inhibitory and co-stimulatory function, depending in part on the specific cell type and immune response course. Though originally described on T cells, Tim-3 is now known to be expressed by both lymphoid and non-lymphoid cells within the immune system and even by non-immune cells. In addition, though widely thought of as a negative regulator of immunity, Tim-3 has been shown in more recent studies to have a positive function on both myeloid and lymphoid cells, including T cells...
2018: F1000Research
Sharon Wei Ling Lee, Giulia Adriani, Erica Ceccarello, Andrea Pavesi, Anthony Tanoto Tan, Antonio Bertoletti, Roger Dale Kamm, Siew Cheng Wong
In the hepatitis B virus (HBV)-related hepatocellular carcinoma tumor microenvironment (TME), monocytes reportedly impede natural T cell functions via PD-L1/PD-1 signaling. However, it remains unclear if T cell receptor-redirected T cells (TCR T cells) are similarly inhibited. Hence, we developed a 3D intrahepatic TME microfluidic model to investigate the immunosuppressive potential of monocytes toward HBV-specific TCR T cells and the role of PD-L1/PD-1 signaling. Interestingly, in our 3D static microfluidic model, we observed that monocytes suppressed only retrovirally transduced (Tdx) TCR T cell cytotoxicity toward cancer cells via PD-L1/PD-1, while mRNA electroporated (EP) TCR T cell cytotoxicity was not affected by the presence of monocytes...
2018: Frontiers in Immunology
Anne Mills, Sara Zadeh, Emily Sloan, Zachary Chinn, Susan C Modesitt, Kari L Ring
Mismatch repair-deficient endometrial carcinomas are optimal candidates for immunotherapy given their high neoantigen loads, robust lymphoid infiltrates, and frequent PD-L1 expression. However, co-opting the PD-1/PD-L1 pathway is just one mechanism that tumors can utilize to evade host immunity. Another immune modulatory molecule that has been demonstrated in endometrial carcinoma is indoleamine 2,3-dioxygenase (IDO). We herein evaluate IDO expression in 60 endometrial carcinomas and assess results in relation to PD-L1 and mismatch repair status...
March 20, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
(no author information available yet)
No abstract text is available yet for this article.
March 20, 2018: Cancer Immunology Research
Shinji Yamada, Shunsuke Itai, Mika K Kaneko, Yukinari Kato
Programmed cell death-ligand 1 (PD-L1), which is a ligand of programmed cell death-1 (PD-1), is a type I transmembrane glycoprotein that is expressed on antigen-presenting cells and several tumor cells, including melanoma and lung cancer cells. There is a strong correlation between human PD-L1 (hPD-L1) expression on tumor cells and negative prognosis in cancer patients. In this study, we produced a novel anti-hPD-L1 monoclonal antibody (mAb), L1 Mab-4 (IgG2b , kappa), using cell-based immunization and screening (CBIS) method and investigated hPD-L1 expression in oral cancers...
March 2018: Biochemistry and Biophysics Reports
Qingxia Yao, Karl P Fischer, D Lorne Tyrrell, Klaus S Gutfreund
Programmed death-1 (PD-1), upon engagement by its ligands, programmed death ligand-1 (PD-L1) and programmed death ligand-2 (PD-L2), provides signals that attenuate adaptive immune responses. Here we describe the identification of the Pekin duck PD-L2 (duPD-L2) and its gene structure. The duPD-L2 cDNA encodes a 321 amino acid protein that has an amino acid identity of 76% and 35% with chicken and human PD-L2, respectively. Mapping of the duPD-L2 cDNA with duck genomic sequences revealed an exonic structure similar to that of the human P dcd1lg2 gene...
March 2018: Biochemistry and Biophysics Reports
Yiming Wang, Rena Ma, Fang Liu, Seul A Lee, Li Zhang
Blockade of programmed death 1 (PD-1) protein and its ligand programmed death ligand 1 (PD-L1) has been used as cancer immunotherapy in recent years, with the blockade of PD-1 being more widely used than blockade of PD-L1. PD-1 and PD-L1 blockade therapy showed benefits in patients with various types of cancer; however, such beneficial effects were seen only in a subgroup of patients. Improving the efficacy of PD-1 and PD-L1 blockade therapy is clearly needed. In this review, we summarize the recent studies on the effects of gut microbiota on PD-1 and PD-L1 blockade and discuss the new perspectives on improving efficacy of PD-1 and PD-L1 blockade therapy in cancer treatment through modulating gut microbiota...
2018: Frontiers in Immunology
Benjamin Benzon, Stephanie A Glavaris, Brian W Simons, Robert M Hughes, Kamyar Ghabili, Patrick Mullane, Rebecca Miller, Katriana Nugent, Brian Shinder, Jeffrey Tosoian, Ephraim J Fuchs, Phuoc T Tran, Paula J Hurley, Milena Vuica-Ross, Edward M Schaeffer, Charles G Drake, Ashley E Ross
BACKGROUND: Prostate cancer remains the second leading cause of cancer related death in men. Immune check point blocking antibodies have revolutionized treatment of multiple solid tumors, but results in prostate cancer remain marginal. Previous reports have suggested that local therapies, in particular cryoablation might increase tumor immunogenicity. In this work, we examine potential synergism between tumor cryoabalation and check point blocking antibodies. METHODS: FVB/NJ mice were injected subcutaneously into each flank with either 1 × 106 or 0...
March 20, 2018: Prostate Cancer and Prostatic Diseases
Annemieke Abel, Christiane Steeg, Francis Aminkiah, Otchere Addai-Mensah, Marylyn Addo, Nicola Gagliani, Christian Casar, Denis Dekugmen Yar, Ellis Owusu-Dabo, Thomas Jacobs, Maria Sophia Mackroth
The immune response of malaria patients is a main factor influencing the clinical severity of malaria. A tight regulation of the CD4+ T cell response or the induction of tolerance have been proposed to contribute to protection from severe or clinical disease. We therefore compared the CD4+ T cell phenotypes of Ghanaian children with complicated malaria, uncomplicated malaria, asymptomatic Plasmodium falciparum (Pf) infection or no infection. Using flow cytometric analysis and automated multivariate clustering, we characterized the expression of the co-inhibitory molecules CTLA-4, PD-1, Tim-3, and LAG-3 and other molecules implicated in regulatory function on CD4+ T cells...
March 19, 2018: Scientific Reports
Linlin Dong, Xiaoyu Zheng, Kun Wang, Guonian Wang, Huichao Zou
BACKGROUND: The T-helper 17 (Th17)/regulatory T (Treg) balance is essential for immune homeostasis. But the effects of gastric surgery on this balance remain unclear. The aim of present study is to identify the influence of gastric surgery on Th17/Treg balance and the role of programmed death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway in this process. METHODS: Mice were divided into Control, Sham and Surgery group randomly. Animals in Surgery group accepted partial gastrectomy...
March 16, 2018: Journal of Trauma and Acute Care Surgery
William Tabayoyong, Jianjun Gao
PURPOSE OF REVIEW: Recent Food and Drug Administration (FDA) approval of five new immune checkpoint inhibitors for the treatment of metastatic urothelial cancer represents the first major treatment breakthrough for this disease since the introduction of combination chemotherapy over 30 years ago. This review examines the recent clinical trials leading to FDA approval of these agents, the current challenges facing immunotherapy and areas that require further research. RECENT FINDINGS: The programmed death 1 receptor (PD-1) and its ligand programmed death ligand-1 (PD-L1) are important negative regulators of immune activity, preventing destruction of normal tissues and autoimmunity...
March 15, 2018: Current Opinion in Oncology
Clémence Granier, Emeline Vinatier, Elia Colin, Marion Mandavit, Charles Dariane, Virginie Verkarre, Lucie Biard, Rami El Zein, Corinne Lesaffre, Isabelle Galy-Fauroux, Hélène Roussel, Eléonore De Guillebon, Charlotte Blanc, Antonin Saldmann, Cécile Badoual, Alain Gey, Éric Tartour
Immune cells are important components of the tumor microenvironment and influence tumor growth and evolution at all stages of carcinogenesis. Notably, it is now well established that the immune infiltrate in human tumors can correlate with prognosis and response to therapy. The analysis of the immune infiltrate in the tumor microenvironment has become a major challenge for the classification of patients and the response to treatment. The co-expression of inhibitory receptors such as Program Cell Death Protein 1 (PD1; also known as CD279), Cytotoxic T Lymphocyte Associated Protein 4 (CTLA-4), T-Cell Immunoglobulin and Mucin Containing Protein-3 (Tim-3; also known as CD366), and Lymphocyte Activation Gene 3 (Lag-3; also known as CD223), is a hallmark of T cell exhaustion...
February 8, 2018: Journal of Visualized Experiments: JoVE
Periklis G Foukas, Sotirios Tsiodras, Panagiota Economopoulou, Aris Spathis, Maria Mademli, Konstantinos Leventakos, Amanda Psyrri, Petros Karakitsos, Ioannis G Panayiotides
The development of immune system modulating agents, such as immune checkpoint inhibitors (ICIs), has revolutionized cancer treatment. Nivolumab, a human monoclonal antibody against PD-1, has emerged as an efficient treatment for various malignancies, including non-small cell lung cancer (NSCLC); however, it is associated with important immune related side-effects, attributed to organ-specific inflammation, such as immune-mediated pneumonitis, a relatively uncommon, albeit potentially fatal adverse event. We herein present the unique case of severe interstitial pneumonitis with concomitant detection of Human Herpes Virus 6 (HHV-6) in a nivolumab treated patient with NSCLC...
2018: IDCases
Junqi Liu, Chuanfeng Zhang, Jiegang Hu, Qing Tian, Xin Wang, Hao Gu, Song Zhang, Di Zhao, Ruitai Fan
Background: Urothelial carcinoma ranks the ninth among malignant cancers. We conducted this study to identify which patients could benefit more from the treatment of programmed death-1 (PD-1)/programmed death-ligand1 (PD-L1) inhibitors. Materials and Methods: We performed literature searches, combined data from qualified literature and performed comparative analyses on the effectiveness of anti-PD-1/PD-L1 antibodies in patients with different PD-L1 expression levels...
February 23, 2018: Oncotarget
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