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https://www.readbyqxmd.com/read/29352490/oral-lichenoid-reaction-showing-multiple-ulcers-associated-with-anti-programmed-death-cell-receptor-1-treatment-a-report-of-two-cases-and-published-work-review
#1
Koya Obara, Mamiko Masuzawa, Yasuyuki Amoh
Anti-programmed cell death receptor-1 (PD-1) antibodies represent an effective treatment opinion for advanced melanoma and non-small-cell lung cancer, as well as other cancerous entities. Immune checkpoint inhibitors such as anti-PD-1 antibody result in a unique side-effect profile, commonly described as immune-related adverse events (irAE). These irAE affect the skin, gastrointestinal tract, liver, endocrine system and other organ systems. We report two cases of oral lichenoid reaction showing multiple ulcers associated with nivolumab treatment...
January 20, 2018: Journal of Dermatology
https://www.readbyqxmd.com/read/29348598/increased-diversity-with-reduced-diversity-evenness-of-tumor-infiltrating-t-cells-for-the-successful-cancer-immunotherapy
#2
Akihiro Hosoi, Kazuyoshi Takeda, Koji Nagaoka, Tamaki Iino, Hirokazu Matsushita, Satoshi Ueha, Shin Aoki, Kouji Matsushima, Masato Kubo, Teppei Morikawa, Kazutaka Kitaura, Ryuji Suzuki, Kazuhiro Kakimi
To facilitate the optimization of cancer immunotherapy lacking immune-related adverse events, we performed TCR repertoire analysis of tumor-infiltrating CD8+ T-cells in B16 melanoma-bearing mice receiving anti-PD-1, anti-CTLA-4, anti-4-1BB, anti-CD4 or a combination of anti-PD-1 and 4-1BB antibodies. Although CD8+ T-cells in the tumor were activated and expanded to a greater or lesser extent by these therapies, tumor growth suppression was achieved only by anti-PD-1, anti-PD-1/4-1BB combined, or by anti-CD4 treatment, but not by anti-CTLA-4 or anti-4-1BB monotherapy...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343435/paracrine-wnt5a-%C3%AE-catenin-signaling-triggers-a-metabolic-program-that-drives-dendritic-cell-tolerization
#3
Fei Zhao, Christine Xiao, Kathy S Evans, Tbalamayooran Theivanthiran, Nicholas DeVito, Alisha Holtzhausen, Juan Liu, Xiaojing Liu, David Boczkowski, Smita Nair, Jason W Locasale, Brent A Hanks
Despite recent advances, many cancers remain refractory to available immunotherapeutic strategies. Emerging evidence indicates that the tolerization of local dendritic cells (DCs) within the tumor microenvironment promotes immune evasion. Here, we have described a mechanism by which melanomas establish a site of immune privilege via a paracrine Wnt5a-β-catenin-peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling pathway that drives fatty acid oxidation (FAO) in DCs by upregulating the expression of the carnitine palmitoyltransferase-1A (CPT1A) fatty acid transporter...
January 16, 2018: Immunity
https://www.readbyqxmd.com/read/29337305/host-expression-of-pd-l1-determines-efficacy-of-pd-l1-pathway-blockade-mediated-tumor-regression
#4
Heng Lin, Shuang Wei, Elaine M Hurt, Michael D Green, Lili Zhao, Linda Vatan, Wojciech Szeliga, Ronald Herbst, Paul W Harms, Leslie A Fecher, Pankaj Vats, Arul M Chinnaiyan, Christopher D Lao, Theodore S Lawrence, Max Wicha, Junzo Hamanishi, Masaki Mandai, Ilona Kryczek, Weiping Zou
Programmed death-1 receptor (PD-L1, B7-H1) and programmed cell death protein 1 (PD-1) pathway blockade is a promising therapy for treating cancer. However, the mechanistic contribution of host and tumor PD-L1 and PD-1 signaling to the therapeutic efficacy of PD-L1 and PD-1 blockade remains elusive. Here, we evaluated 3 tumor-bearing mouse models that differ in their sensitivity to PD-L1 blockade and demonstrated a loss of therapeutic efficacy of PD-L1 blockade in immunodeficient mice and in PD-L1- and PD-1-deficient mice...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29333023/nivolumab-pearls-of-evidence
#5
REVIEW
Pratishtha B Chaudhari
Purpose: Nivolumab is one of the most extensively studied immune checkpoint inhibitors across various tumor types. In this narrative review, the current clinical efficacy and safety data of anti-programmed death-1 (PD-1) nivolumab for nonsmall cell lung cancer (NSCLC) and renal cell cancer (RCC) are elucidated. Methods: Systematic search was done on Pubmed, Medline, Embase, Web of Knowledge, and Cochrane Central through September 2016 for controlled prospective interventional studies of nivolumab across two indications - NSCLC and RCC...
October 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/29331748/safety-and-efficacy-of-anti-programmed-death-1-antibodies-in-patients-with-cancer-and-pre-existing-autoimmune-or-inflammatory-disease
#6
François-Xavier Danlos, Anne-Laure Voisin, Valérie Dyevre, Jean-Marie Michot, Emilie Routier, Laurent Taillade, Stéphane Champiat, Sandrine Aspeslagh, Julien Haroche, Laurence Albiges, Christophe Massard, Nicolas Girard, Stéphane Dalle, Benjamin Besse, Salim Laghouati, Jean-Charles Soria, Christine Mateus, Caroline Robert, Emilie Lanoy, Aurélien Marabelle, Olivier Lambotte
OBJECTIVE: Patients with autoimmune or inflammatory disease (AID) are susceptible to immune-related adverse events (irAEs) when treated with immune check-point inhibitors (ICIs). We decided to analyse the safety and effectiveness of anti-PD-1 antibodies in AID patients and look for an association between the presence of pre-existing AID and the clinical outcome. METHODS: In a prospective study of the REISAMIC registry of grade ≥2 irAEs occurring in ICI-treated patients, we studied the associations between pre-existing AID on one hand and irAE-free survival, overall survival and best objective response rate on the other...
January 10, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29326088/age-effects-of-distinct-immune-checkpoint-blockade-treatments-in-a-mouse-melanoma-model
#7
Álvaro Padrón, Vincent Hurez, Harshita B Gupta, Curtis A Clark, Sri Lakshmi Pandeswara, Bin Yuan, Robert S Svatek, Mary Jo Turk, Justin M Drerup, Rong Li, Tyler J Curiel
Cancer immunotherapy has shown remarkable recent progress. Immune checkpoint blocking antibodies have become the most successful anti-cancer agent class ever developed, with six distinct agents approved since 2011 for a wide variety of cancers. Although age is the biggest risk factor for cancer (aside from selected early-onset pediatric cancers), these agents were tested pre-clinically in young hosts, and there is remarkably little published on the effects of host age on treatment outcomes in pre-clinical studies or human clinical trials...
January 8, 2018: Experimental Gerontology
https://www.readbyqxmd.com/read/29317734/combined-sep-and-anti-pd-l1-antibody-produces-a-synergistic-antitumor-effect-in-b16-f10-melanoma-bearing-mice
#8
Zhengping Hu, Liang Ye, Yingying Xing, Jinhang Hu, Tao Xi
The increased PD-L1 induces poorer prognosis in melanoma. The treatment with PD-1/PD-L1 antibodies have a low response rate. The combination immunotherapies are the encouraging drug development strategy to receive maximal therapeutic benefit. In this study, we investigated the enhanced antitumor and immunomodulatory activity of combined SEP and αPD-L1 in B16-F10 melanoma-bearing mice. The results shown that combined SEP and αPD-L1 presented significant synergistic antitumor effects, increased the frequency of CD8+ and CD4+ T cells in spleen and tumor, cytotoxic activity of CTL in spleen, and IL-2 and IFN-γ levels in splenocytes and tumor...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29302014/the-commensal-microbiome-is-associated-with-anti-pd-1-efficacy-in-metastatic-melanoma-patients
#9
Vyara Matson, Jessica Fessler, Riyue Bao, Tara Chongsuwat, Yuanyuan Zha, Maria-Luisa Alegre, Jason J Luke, Thomas F Gajewski
Anti-PD-1-based immunotherapy has had a major impact on cancer treatment but has only benefited a subset of patients. Among the variables that could contribute to interpatient heterogeneity is differential composition of the patients' microbiome, which has been shown to affect antitumor immunity and immunotherapy efficacy in preclinical mouse models. We analyzed baseline stool samples from metastatic melanoma patients before immunotherapy treatment, through an integration of 16S ribosomal RNA gene sequencing, metagenomic shotgun sequencing, and quantitative polymerase chain reaction for selected bacteria...
January 5, 2018: Science
https://www.readbyqxmd.com/read/29301578/notch1-signaling-in-melanoma-cells-promoted-tumor-induced-immunosuppression-via-upregulation-of-tgf-%C3%AE-1
#10
Zike Yang, Yanxia Qi, Nan Lai, Jiahe Zhang, Zehong Chen, Mingyu Liu, Wan Zhang, Rongcheng Luo, Shijun Kang
BACKGROUND: The receptors of Notch family play an important role in controlling the development, differentiation, and function of multiple cell types. The aim of this study is to investigate the role of Notch1 signaling upon immune suppression induced by melanoma cells. METHODS: Melanoma cell line B16 cells were transfected by lentivirus containing mouse Notch1 gene or Notch1 shRNA to generate B16 cell line that highly or lowly expressed Notch1. Notch1 in anti-tumor immune response was comprehensively appraised in murine B16 melanoma tumor model in immunocompetent and immunodeficient mice...
January 4, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29297903/-pembrolizumab-for-the-treatment-of-melanoma-updates-and-perspectives
#11
Vanna Chiarion Sileni, Mario Mandalà, Paola Queirolo
Checkpoint inhibitors immunotherapy was a breakthrough in anti-tumor treatments. Anti-PD-1 monoclonal antibodies are now a standard of treatment for advanced melanoma patients, with a 3-year overall survival of over 50% and a low rate (<20%) of severe toxicities in the phase 3 studies. The aim of this review was to report the most important updates on anti-PD-1 drug pembrolizumab from ASCO (American Society of Clinical Oncology) and ESMO (European Society for Medical Oncology) 2017 Annual Meetings.
December 2017: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/29297899/-combination-strategies-in-melanoma-therapy
#12
Francesco Spagnolo
Immune checkpoint inhibitors led to major advances in melanoma therapy, and pembrolizumab (anti-PD-1 monoclonal antibody) is now a new standard of treatment for advanced melanoma. The aim of this work was to discuss, on the basis of planned or ongoing clinical trials, future perspectives to improve the efficacy of pembrolizumab, such as combination regimens with other immunotherapies or targeted therapies.
December 2017: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/29289977/anti-pd-1-induced-high-grade-hepatitis-associated-with-corticosteroid-resistant-t-cells-a-case-report
#13
Helen M McGuire, Elena Shklovskaya, Jarem Edwards, Paul R Trevillian, Geoffrey W McCaughan, Patrick Bertolino, Catriona McKenzie, Ralph Gourlay, Stuart J Gallagher, Barbara Fazekas de St Groth, Peter Hersey
Effective treatment or prevention of immune side effects associated with checkpoint inhibitor therapy of cancer is an important goal in this new era of immunotherapy. Hepatitis due to immunotherapy with antibodies against PD-1 is uncommon and generally of low severity. We present an unusually severe case arising in a melanoma patient after more than 6 months uncomplicated treatment with anti-PD-1 in an adjuvant setting. The hepatitis rapidly developed resistance to high-dose steroids, requiring anti-thymocyte globulin (ATG) to achieve control...
December 30, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29277453/sarcoidosis-post-anti-pd-1-therapy-mimicking-relapse-of-metastatic-melanoma-in-a-patient-undergoing-complete-remission
#14
N Yatim, C Mateus, P Charles
Novel treatments of metastatic melanoma include the usage of checkpoint inhibitors such as anti-cytotoxic-T-lymphocyte-associated antigen (CTLA-4) or anti-programmed death-1 (PD-1) antibodies, which are immunomodulatory antibodies that enhance the immune response against tumors. While they have substantially improved the prognosis for patients, these therapies are associated with a large spectrum of immune-related adverse effects (irAEs). We report a patient developing pulmonary and cutaneous sarcoidosis after pembrolizumab therapy while complete regression of stage IV melanoma was perceived...
December 22, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/29275462/cancer-immunotherapy-targets-based-on-understanding-the-t-cell-inflamed-versus-non-t-cell-inflamed-tumor-microenvironment
#15
Thomas F Gajewski, Leticia Corrales, Jason Williams, Brendan Horton, Ayelet Sivan, Stefani Spranger
Most cancers express tumor antigens that can be recognized by T cells of the host. The fact that cancers become clinically evident nonetheless implies that immune escape must occur. Two major subsets of human melanoma metastases have been identified based on gene expression profiling. One subgroup has a T cell-inflamed phenotype that includes expression of chemokines, T cell markers, and a type I IFN signature. In contrast, the other major subset lacks this phenotype and has been designated as non-T cell-inflamed...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29274233/efficacy-of-anti-pd-1-on-skin-carcinomas-and-melanoma-metastases-in-an-xeroderma-pigmentosum-patient
#16
G Salomon, A Maza, S Boulinguez, C Paul, L Lamant, E Tournier, J Mazereeuw-Hautier, N Meyer
Xeroderma pigmentosum is an orphan disease of poor prognosis. We report one case of parallel efficacy with anti-PD-1 antibody on both melanoma and skin carcinoma in a xeroderma pigmentosum patient. A 17-year old patient presented with metastatic melanoma and multiple non melanoma skin cancers. He was treated with pembrolizumab, a monoclonal anti-PD-1 antibody, at the dose of 2mg/Kg 3 weeks apart. Parallel therapeutic efficacy of anti-PD1 was observed in metastatic melanoma and skin carcinomas, and maintained at week 24...
December 23, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/29273790/tnf%C3%AE-blockade-overcomes-resistance-to-anti-pd-1-in-experimental-melanoma
#17
Florie Bertrand, Anne Montfort, Elie Marcheteau, Caroline Imbert, Julia Gilhodes, Thomas Filleron, Philippe Rochaix, Nathalie Andrieu-Abadie, Thierry Levade, Nicolas Meyer, Céline Colacios, Bruno Ségui
Antibodies against programmed cell death-1 (PD-1) have considerably changed the treatment for melanoma. However, many patients do not display therapeutic response or eventually relapse. Moreover, patients treated with anti-PD-1 develop immune-related adverse events that can be cured with anti-tumor necrosis factor α (TNF) antibodies. Whether anti-TNF antibodies affect the anti-cancer immune response remains unknown. Our recent work has highlighted that TNFR1-dependent TNF signalling impairs the accumulation of CD8+ tumor-infiltrating T lymphocytes (CD8+ TILs) in mouse melanoma...
December 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/29250533/pd-l1-promotes-self-renewal-and-tumorigenicity-of-malignant-melanoma-initiating-cells
#18
Fang Zheng, Jianzhong Dang, Hui Zha, Bingyu Zhang, Ming Lin, Fanjun Cheng
Recent studies have indicated that therapeutic antibodies targeting PD-L1 show remarkable efficacy in clinical trials in multiple tumors and that a melanoma cell-intrinsic PD-1: PD-L1 axis promotes tumor growth. However, few studies have shown tumor-intrinsic PD-L1 effects in malignant melanoma initiating cells (MMICs). Here, we aim to determine the possible regulatory effects of PD-L1 on MMICs. The ALDEFLUOR kit was used to identify ALDH+ MMICs. Flow cytometry was used to examine the expression of PD-L1 on ALDH+ MMICs...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29250451/hypokalemic-paralysis-secondary-to-immune-checkpoint-inhibitor-therapy
#19
Pragathi Balakrishna, Augusto Villegas
Introduction of immune checkpoint inhibitors (ICIs) has led to significant improvements in the treatment of multiple malignancies. Anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) are two essential ICIs that have been FDA approved since 2011. As the use of immunotherapy in melanoma and other malignancies increases, the potential of adverse events also increases. Overall, anti-PD-1 agents are well tolerated. In rare instances, colitis, endocrinopathies, skin, and renal toxicities have been observed...
2017: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/29239193/-checkpoint-inhibitors-in-the-treatment-of-upper-gastrointestinal-tract-tumors
#20
R Obermannova
Chemotherapy prolongs overall survival (OS) in esophageal (EC) and gastric cancer (GC). Unsatisfactory results of systemic therapy initiated a search for new treatment options. In metastatic disease, a number of targeted drugs were tested; however, several phase III studies assessing receptor tyrosin kinase-related signaling pathways, such as EGFR, MET/HGF or mTOR, failed. Trastuzumab remains the only targeted drug with a known molecular predictor, which extended the OS in metastatic gastric adenocarcinoma and adenocarcinoma of esophago-gastric junction...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
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