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Melanoma pd-1

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https://www.readbyqxmd.com/read/29455872/-pd-l1-expression-and-pd-1-pd-l1-inhibitors-in-breast-cancer
#1
REVIEW
Audrey Monneur, Anthony Gonçalves, François Bertucci
The development of immune checkpoints inhibitors represents one of the major recent advances in oncology. Monoclonal antibodies directed against the programmed cell death protein 1 (PD-1) or its ligand (PD-L1) provides durable disease control, particularly in melanoma, lung, kidney, bladder and head and neck cancers. The purpose of this review is to synthesize current data on the expression of PD-L1 in breast cancer and on the preliminary clinical results of PD-1/PD-L1 inhibitors in breast cancer patients. In breast cancer, PD-L1 expression is heterogeneous and is generally associated with the presence of tumor-infiltrating lymphocytes as well as the presence of poor-prognosis factors, such as young age, high grade, ER-negativity, PR-negativity, and HER-2 overexpression, high proliferative index, and aggressive molecular subtypes (triple negative, basal-like, HER-2-overexpressing)...
February 15, 2018: Bulletin du Cancer
https://www.readbyqxmd.com/read/29453278/molecular-signatures-of-circulating-melanoma-cells-for-monitoring-early-response-to-immune-checkpoint-therapy
#2
Xin Hong, Ryan J Sullivan, Mark Kalinich, Tanya Todorova Kwan, Anita Giobbie-Hurder, Shiwei Pan, Joseph A LiCausi, John D Milner, Linda T Nieman, Ben S Wittner, Uyen Ho, Tianqi Chen, Ravi Kapur, Donald P Lawrence, Keith T Flaherty, Lecia V Sequist, Sridhar Ramaswamy, David T Miyamoto, Michael Lawrence, Mehmet Toner, Kurt J Isselbacher, Shyamala Maheswaran, Daniel A Haber
A subset of patients with metastatic melanoma have sustained remissions following treatment with immune checkpoint inhibitors. However, analyses of pretreatment tumor biopsies for markers predictive of response, including PD-1 ligand (PD-L1) expression and mutational burden, are insufficiently precise to guide treatment selection, and clinical radiographic evidence of response on therapy may be delayed, leading to some patients receiving potentially ineffective but toxic therapy. Here, we developed a molecular signature of melanoma circulating tumor cells (CTCs) to quantify early tumor response using blood-based monitoring...
February 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29450544/hla-class-i-antigen-expression-in-conjunctival-melanoma-is-not-associated-with-pd-l1-pd-1-status
#3
Jinfeng Cao, Niels J Brouwer, Ekaterina S Jordanova, Marina Marinkovic, Sjoerd G van Duinen, Nadine E de Waard, Bruce R Ksander, Arend Mulder, Frans H J Claas, Mirjam H M Heemskerk, Martine J Jager
Purpose: Antitumor T cells need expression of HLA class I molecules but can be inhibited by ligands such as programmed death ligand 1 (PD-L1). We determined expression and regulation of these molecules in human conjunctival melanoma (CM) samples, cell lines, and murine xenografts. Methods: Immunofluorescence staining was performed to examine the expression of HLA-A, HLA-B/C, and β-2-microglobulin (B2M) in 23 primary CM samples. HLA class I expression was compared with clinicopathologic characteristics, the presence of tumor-infiltrating leukocytes, and PD-L1/PD-1 status...
February 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29433557/metastatic-uveal-melanoma-showing-durable-response-to-anti-ctla-4-and-anti-pd-1-combination-therapy-after-experiencing-progression-on-anti-pd-1-therapy-alone
#4
Muhammad Zubair Afzal, Rodwell Mabaera, Keisuke Shirai
BACKGROUND: Uveal melanoma accounts for 85% of the ocular melanomas and has an increased risk of hematogenous spread, most commonly to the liver. After curative intent therapy like surgery and radiation, fifty percent of patients present with distant metastasis. Metastatic uveal melanoma (MUM) does not harbor typically targetable mutations, e.g., BRAF as in cutaneous melanoma. As a result, there is no proven therapy for MUM. Various chemotherapy and immunotherapy regimens have been tried and only partial response (PR) is the best that has been achieved in most of the cases...
February 12, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29432222/immunotherapy-for-recurrent-metastatic-head-and-neck-cancer
#5
Salvatore Alfieri, Stefano Cavalieri, Lisa Licitra
PURPOSE OF REVIEW: In the last decade, after cetuximab (anti-epidermal growth factor receptor), none of the novel investigated compounds has demonstrated benefit in head and neck squamous cell cancers (HNSCC), both in advanced and curative settings. Therefore, prognosis of recurrent/metastatic (R/M) HNSCC patients remains dismal, especially in platinum-refractory cohort. In the last few years, a new important class of drugs has affirmed its role. HNSCC, even if less 'immunogenic' than other malignancies (e...
February 8, 2018: Current Opinion in Otolaryngology & Head and Neck Surgery
https://www.readbyqxmd.com/read/29431745/dkk2-imparts-tumor-immunity-evasion-through-%C3%AE-catenin-independent-suppression-of-cytotoxic-immune-cell-activation
#6
Qian Xiao, Jibo Wu, Wei-Jia Wang, Shiyang Chen, Yingxia Zheng, Xiaoqing Yu, Katrina Meeth, Mahnaz Sahraei, Alfred L M Bothwell, Lieping Chen, Marcus Bosenberg, Jianfeng Chen, Veronika Sexl, Le Sun, Lin Li, Wenwen Tang, Dianqing Wu
Immunotherapy offers new options for cancer treatment, but efficacy varies across cancer types. Colorectal cancers (CRCs) are largely refractory to immune-checkpoint blockade, which suggests the presence of yet uncharacterized immune-suppressive mechanisms. Here we report that the loss of adenomatosis polyposis coli (APC) in intestinal tumor cells or of the tumor suppressor PTEN in melanoma cells upregulates the expression of Dickkopf-related protein 2 (DKK2), which, together with its receptor LRP5, provides an unconventional mechanism for tumor immune evasion...
February 12, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29425258/expression-of-programmed-death-ligand-1-pd-l1-in-posttreatment-primary-inflammatory-breast-cancers-and-clinical-implications
#7
Jing He, Lei Huo, Junsheng Ma, Jun Zhao, Roland L Bassett, Xiaoping Sun, Naoto T Ueno, Bora Lim, Yun Gong
Objectives: Inflammatory breast carcinoma (IBC) is rare but is the most lethal type of breast cancer. Programmed death ligand 1 (PD-L1) expression in IBCs has been understudied. Methods: In this study, tissue microarrays of 68 IBCs were immunostained with a PD-L1 antibody using an antibody clone (28-8) and detection system approved by the US Food and Drug Administration for selecting patients with non-small cell lung cancer and melanoma for anti-PD-L1 therapy. Results: Positive PD-L1 expression was found in 25 (36...
February 7, 2018: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29424425/correlation-between-sex-and-efficacy-of-immune-checkpoint-inhibitors-pd-1-and-ctla-4-inhibitors
#8
Yingcheng Wu, Qianqian Ju, Keren Jia, Jingyan Yu, Hui Shi, Huiqun Wu, Maorong Jiang
Immune checkpoint inhibitors (ICIs) exert the antitumor efficacy depending on immune response, which is affected by sex difference, where both biological and sociological factors are involved. The role of sex in ICI trials has been overlooked. How sex correlates with ICI efficacy is incompletely understood. Clinical trials evaluating ICI versus other therapies in male and female patients were included. The hazard ratio (HR) and 95% confidence interval (CI) of overall survival (OS) and progression-free survival (PFS) were used...
February 9, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29423503/association-between-circulating-tumor-dna-and-pseudoprogression-in-patients-with-metastatic-melanoma-treated-with-anti-programmed-cell-death-1-antibodies
#9
Jenny H Lee, Georgina V Long, Alexander M Menzies, Serigne Lo, Alexander Guminski, Kataraina Whitbourne, Michelle Peranec, Richard Scolyer, Richard F Kefford, Helen Rizos, Matteo S Carlino
Importance: Longitudinal circulating tumor DNA (ctDNA) has been shown to predict response and survival in patients with metastatic melanoma treated with anti-programmed cell death 1 (PD-1) antibodies. Pseudoprogression, defined as radiologic finding of disease progression prior to response, has been a challenge to clinicians. Objective: To establish whether ctDNA at baseline and up to week 12 of treatment can differentiate between the radiologic findings of pseudoprogression and true progression in patients with metastatic melanoma...
February 8, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29423067/inhibition-of-tumor-growth-by-cancer-vaccine-combined-with-metronomic-chemotherapy-and-anti-pd-1-in-a-pre-clinical-setting
#10
Annacarmen Petrizzo, Angela Mauriello, Antonio Luciano, Domenica Rea, Antonio Barbieri, Claudio Arra, Piera Maiolino, Marialina Tornesello, Vincenzo Gigantino, Gerardo Botti, Gennaro Ciliberto, Franco M Buonaguro, Maria Tagliamonte, Luigi Buonaguro
Tumor microenvironment (TME) is characterized by multiple immune suppressive mechanisms able to suppress anti-tumor effector cell immunity. Combinatorial strategies, including vaccine and immunomodulatory drugs, need to be developed for improved immunotherapy efficacy. A novel combinatorial approach was assessed in C57BL/6 mice injected with mouse melanoma B16F10 cells. A multi-peptide vaccine (PEPT) was combined with a low dose metronomic chemotherapy (MCT) and an anti-PD-1 checkpoint inhibitor (CI). Statistical analysis were performed with the unpaired two-sided Student's t-test and ANOVA...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29406396/safety-and-efficacy-of-anti-pd-1-therapy-for-metastatic-melanoma-and-non-small-cell-lung-cancer-in-patients-with-viral-hepatitis-a-case-series
#11
Anita Kothapalli, Muhammad A Khattak
Anti-PD-1 monoclonal antibodies have shown durable long-term survival benefit in patients with metastatic melanoma. Limited evidence exists on the safety and efficacy of PD-1 inhibitors in patients with hepatitis B virus (HBV) and hepatitis C virus (HCV) infections as these patients have traditionally been excluded from clinical trials because of a theoretical risk of immune reconstitution inflammatory syndrome. We aim to determine the safety and efficacy of treatment with PD-1 inhibitors in seven patients with HBV/HCV infection and concurrent metastatic melanoma or non-small-cell lung cancer (NSCLC)...
February 5, 2018: Melanoma Research
https://www.readbyqxmd.com/read/29403496/recent-advances-in-targeting-cd8-t-cell-immunity-for-more-effective-cancer-immunotherapy
#12
REVIEW
Aurélie Durgeau, Yasemin Virk, Stéphanie Corgnac, Fathia Mami-Chouaib
Recent advances in cancer treatment have emerged from new immunotherapies targeting T-cell inhibitory receptors, including cytotoxic T-lymphocyte associated antigen (CTLA)-4 and programmed cell death (PD)-1. In this context, anti-CTLA-4 and anti-PD-1 monoclonal antibodies have demonstrated survival benefits in numerous cancers, including melanoma and non-small-cell lung carcinoma. PD-1-expressing CD8+ T lymphocytes appear to play a major role in the response to these immune checkpoint inhibitors (ICI). Cytotoxic T lymphocytes (CTL) eliminate malignant cells through recognition by the T-cell receptor (TCR) of specific antigenic peptides presented on the surface of cancer cells by major histocompatibility complex class I/beta-2-microglobulin complexes, and through killing of target cells, mainly by releasing the content of secretory lysosomes containing perforin and granzyme B...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29401166/the-risk-of-diarrhea-and-colitis-in-patients-with-advanced-melanoma-undergoing-immune-checkpoint-inhibitor-therapy-a-systematic-review-and-meta-analysis
#13
Parul Tandon, Samuel Bourassa-Blanchette, Kirles Bishay, Simon Parlow, Scott A Laurie, Jeffrey D McCurdy
Checkpoint inhibitors are a first-line therapy for advanced melanoma, though their use is limited by diarrhea and colitis. The aim of our study was to determine the risk of these toxicities associated with immunotherapy in advanced melanoma. Electronic databases were searched through June 2017 for prospective studies reporting the risk of diarrhea and colitis in advanced melanoma treated with anti-programmed death-1 (PD-1) or anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors. Standardized definitions assessed the grade of diarrhea and colitis...
February 2, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29399407/beta-blocker-use-correlates-with-better-overall-survival-in-metastatic-melanoma-patients-and-improves-the-efficacy-of-immunotherapies-in-mice
#14
Kathleen M Kokolus, Ying Zhang, Jeffrey M Sivik, Carla Schmeck, Junjia Zhu, Elizabeth A Repasky, Joseph J Drabick, Todd D Schell
Immunotherapy has expanded treatment options for cancers with historically poor outcomes, yet a significant proportion of patients still fail to achieve durable clinical benefit. We defined the contribution of β-adrenergic receptor (βAR) signaling, a component of the stress response, on success of immunotherapy for melanoma since the use of antagonists (β-blockers) is associated with improved clinical outcomes in some cancers. We show that metastatic melanoma patients who received immunotherapy had improved overall survival if they also received pan β-blockers...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399391/dendritic-cell-vaccine-induces-antigen-specific-cd8-t-cells-that-are-metabolically-distinct-from-those-of-peptide-vaccine-and-is-well-combined-with-pd-1-checkpoint-blockade
#15
Koji Nagaoka, Akihiro Hosoi, Tamaki Iino, Yasuyuki Morishita, Hirokazu Matsushita, Kazuhiro Kakimi
The success of immune checkpoint blockade has unequivocally demonstrated that anti-tumor immunity plays a pivotal role in cancer therapy. Because endogenous tumor-specific T-cell responsiveness is essential for the success of checkpoint blockade, combination therapy with cancer vaccination may facilitate tumor rejection. To select the best vaccine strategy to combine with checkpoint blockade, we compared dendritic cell-based vaccines (DC-V) with peptide vaccines for induction of anti-tumor immunity that could overcome tumor-induced immunosuppression...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29396710/n-acetyl-cysteine-protects-anti-melanoma-cytotoxic-t-cells-from-exhaustion-induced-by-rapid-expansion-via-the-downmodulation-of-foxo1-in-an-akt-dependent-manner
#16
Matthew J Scheffel, Gina Scurti, Megan M Wyatt, Elizabeth Garrett-Mayer, Chrystal M Paulos, Michael I Nishimura, Christina Voelkel-Johnson
Therapeutic outcomes for adoptive cell transfer (ACT) therapy are constrained by the quality of the infused T cells. The rapid expansion necessary to obtain large numbers of cells results in a more terminally differentiated phenotype with decreased durability and functionality. N-acetyl cysteine (NAC) protects against activation-induced cell death (AICD) and improves anti-tumor efficacy of Pmel-1 T cells in vivo. Here, we show that these benefits of NAC can be extended to engineered T cells and significantly increases T-cell survival within the tumor microenvironment...
February 2, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29392770/the-good-the-not-so-bad-and-the-ugly-of-immune-homeostasis-in-melanoma
#17
REVIEW
Jessica da Gama Duarte, Katherine Woods, Miles C Andrews, Andreas Behren
Within the immune system multiple mechanisms balance the need for efficient pathogen recognition and destruction with the prevention of tissue damage by excessive, inappropriate or even self-targeting (auto)immune reactions. This immune homeostasis is a tightly regulated system which fails during tumor development, often due to the hijacking of its essential self-regulatory mechanisms by cancer cells. It is facilitated not only by tumor intrinsic properties, but also by the microbiome, host genetics and other factors...
February 2, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29390572/acute-liver-failure-caused-by-pembrolizumab-in-a-patient-with-pulmonary-metastatic-liver-cancer-a-case-report
#18
Zhenping Wu, Lingling Lai, Ming Li, Lunli Zhang, Wenfeng Zhang
RATIONALE: Keytruda (pembrolizumab) is an inhibitor of programmed cell death receptor-1 (PD-1), which was approved to treat advanced melanoma and nonsmall cell lung cancer patients who do not respond to other treatment. However, its efficacy and security in the treatment of advanced liver cancer is still under investigation. PATIENT CONCERNS: A 60-year-old man was diagnosed with pulmonary metastatic liver cancer who accepted pembrolizumab treatment after the failure of sorafenib...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29388007/the-role-of-tumor-infiltrating-lymphocytes-tils-as-a-predictive-biomarker-of-response-to-anti-pd1-therapy-in-patients-with-metastatic-non-small-cell-lung-cancer-or-metastatic-melanoma
#19
Anton Uryvaev, Maria Passhak, Dov Hershkovits, Edmond Sabo, Gil Bar-Sela
Immunotherapy plays an important role in cancer treatment. Biomarkers that can predict response, including tumor-infiltrating lymphocytes (TILs), are in the spotlight of many studies. This cohort study was designed to evaluate the role of CD4+ and CD8+ TILs as predictive factors for response to anti PD-1 treatment in patients with metastatic non-small cell lung cancer (NSCLC) or metastatic melanoma. We evaluated the expression of CD4+ and CD8+ TILs in tissue samples of 56 patients with metastatic NSCLC or melanoma treated with anti-PD1 immunotherapy...
January 31, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29386395/anti-pd-1-anti-ctla-4-efficacy-in-melanoma-brain-metastases-depends-on-extracranial-disease-and-augmentation-of-cd8-t-cell-trafficking
#20
David Taggart, Tereza Andreou, Karen J Scott, Jennifer Williams, Nora Rippaus, Rebecca J Brownlie, Elizabeth J Ilett, Robert J Salmond, Alan Melcher, Mihaela Lorger
Inhibition of immune checkpoints programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) on T cells results in durable antitumor activity in melanoma patients. Despite high frequency of melanoma brain metastases (BrM) and associated poor prognosis, the activity and mechanisms of immune checkpoint inhibitors (ICI) in metastatic tumors that develop within the "immune specialized" brain microenvironment, remain elusive. We established a melanoma tumor transplantation model with intracranial plus extracranial (subcutaneous) tumor, mimicking the clinically observed coexistence of metastases inside and outside the brain...
January 31, 2018: Proceedings of the National Academy of Sciences of the United States of America
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