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Immune checkpoint therapy

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https://www.readbyqxmd.com/read/27922697/regulation-of-pd-l1-expression-in-a-high-grade-invasive-human-oral-squamous-cell-carcinoma-microenvironment
#1
Mariko Hirai, Hiroko Kitahara, Yutaka Kobayashi, Koroku Kato, George Bou-Gharios, Hiroyuki Nakamura, Shuichi Kawashiri
Blockade of the programmed-death 1 receptor (PD-1)/programmed-death ligand (PD-L1) pathway efficiently reduces tumour growth and improves survival. Durable tumour regression with blockade of the PD-1/PD-L1 checkpoint has been demonstrated in recent clinical studies. Oral squamous cell carcinoma (OSCC) is highly immunosuppressive, and PD-L1 expression has been proposed as a potential mechanism responsible for this phenotype. Despite the fact that anti-PD-1 treatment can produce durable responses, such therapy appears to benefit only a subset of patients...
December 2, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27921007/long-term-response-to-nivolumab-and-acute-renal-failure-in-a-patient-with-metastatic-papillary-renal-cell-carcinoma-and-a-pd-l1-tumor-expression-increased-with-sunitinib-therapy-a-case-report
#2
Juan Ruiz-Bañobre, Urbano Anido, Ihab Abdulkader, José Antúnez-López, Rafael López-López, Jorge García-González
INTRODUCTION: Papillary renal cell carcinoma (PRCC), which represents around 20% of renal cell carcinomas, is a heterogeneous disease that includes different tumor types with several clinical and molecular phenotypes. Nivolumab, a fully human IgG4 programed cell death protein 1 immune checkpoint inhibitor antibody, has shown not only an overall survival advantage when compared to everolimus but also a relatively good side-effect profile among patients with previously treated advanced or metastatic renal cell carcinoma...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27920706/ipilimumab-induced-enteritis-without-colitis-a-new-challenge
#3
Marcus Messmer, Sunita Upreti, Yaman Tarabishy, Nikhilesh Mazumder, Reezwana Chowdhury, Mark Yarchoan, Matthias Holdhoff
INTRODUCTION: Ipilimumab is an immune checkpoint inhibitor targeting cytotoxic T-lymphocyte associated antigen 4 (CTLA4), approved to treat metastatic melanoma. It was the first therapy shown to prolong survival in a large, randomized clinical trial. However, immune-related adverse events are common and can be severe. Enterocolitis is a common adverse event with ipilimumab, but enteritis without colitis has not been previously described. CASE REPORT: An 83-year-old man presented to our hospital with grade 3 diarrhea for 5 days...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/27920704/autoimmune-hemolytic-anemia-as-a-complication-of-nivolumab-therapy
#4
Amruth R Palla, Devin Kennedy, Hossain Mosharraf, Donald Doll
Recently, immunotherapeutic drugs, including PD-1 inhibitors (nivolumab, pembrolizumab), PD-L1 inhibitors (atezolizumab, avelumab), and CTLA4 inhibitors (ipiliumumab), have emerged as important additions to the armamentarium against certain malignancies and have been incorporated into therapeutic protocols for first-, second-, or third-line agents for these metastatic cancers. Immune checkpoint inhibitor nivolumab is currently FDA approved for the treatment of patients with metastatic malignant melanoma [Redman et al...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/27920468/immune-checkpoint-therapy-for-pancreatic-cancer
#5
REVIEW
Henrik Johansson, Roland Andersson, Monika Bauden, Sarah Hammes, Stefan Holdenrieder, Daniel Ansari
Novel treatment modalities are necessary for pancreatic cancer. Immunotherapy with immune checkpoint inhibition has shown effect in other solid tumors, and could have a place in pancreatic cancer treatment. Most available clinical studies on immune checkpoint inhibitors for pancreatic cancer are not yet completed and are still recruiting patients. Among the completed trials, there have been findings of a preliminary nature such as delayed disease progression and enhanced overall survival after treatment with immune checkpoint inhibitors in mono- or combination therapy...
November 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27917363/future-therapy-for-hepatitis-b-virus-role-of-immunomodulators
#6
REVIEW
Edward A Pham, Ryan B Perumpail, Benjamin J Fram, Jeffrey S Glenn, Aijaz Ahmed, Robert G Gish
Although currently available therapies for chronic hepatitis B virus infection can suppress viremia and provide long-term benefits for patients, they do not lead to a functional cure for most patients. Advances in our understanding of the virus-host interaction and the recent remarkable success of immunotherapy in cancer offer new and promising strategies for developing immune modulators that may become important components of a total therapeutic approach to hepatitis B, some of which are now in clinical development...
2016: Current Hepatology Reports
https://www.readbyqxmd.com/read/27916137/cancer-mutational-load-the-more-the-merrier-for-immune-checkpoint-blockade-therapies
#7
EDITORIAL
(no author information available yet)
No abstract text is available yet for this article.
November 2016: EBioMedicine
https://www.readbyqxmd.com/read/27913998/immunotherapy-for-breast-cancer-past-present-and-future
#8
Alison Spellman, Shou-Ching Tang
Immunotherapy has shown promise in many solid tumors including melanoma and non-small cell lung cancer with an evolving role in breast cancer. Immunotherapy encompasses a wide range of therapies including immune checkpoint inhibition, monoclonal antibodies, bispecific antibodies, vaccinations, antibody-drug conjugates, and identifying other emerging interventions targeting the tumor microenvironment. Increasing efficacy of these treatments in breast cancer patients requires identification of better biomarkers to guide patient selection; recognizing when to initiate these therapies in multi-modality treatment plans; establishing novel assays to monitor immune-mediated responses; and creating combined systemic therapy options incorporating conventional treatments such as chemotherapy and endocrine therapy...
December 2, 2016: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/27913861/cxcl12-expression-and-pd-l1-expression-serve-as-prognostic-biomarkers-in-hcc-and-are-induced-by-hypoxia
#9
Alexander Semaan, Dimo Dietrich, Dominik Bergheim, Jörn Dietrich, Jörg C Kalff, Vittorio Branchi, Hanno Matthaei, Glen Kristiansen, Hans-Peter Fischer, Diane Goltz
Anti-PD-1 treatment increases anti-tumour immune responses in animal models of hepatocellular carcinoma (HCC). Sorafenib, the mainstay of treatment of HCC patients, however, leads to tumour hypoxia and thereby abrogates the efficacy of anti-PD-1 treatment. This served as a rationale to implement CXCR4 inhibition as adjunct to sorafenib and anti-PD-1 treatment in murine HCC models. We studied the relationship between tumour hypoxia, PD-L1 and CXCL12 expression in human HCC, aiming to test the rationale for triple therapy combining sorafenib, PD-1 immune checkpoint inhibitors and CXCR4 inhibitors...
December 2, 2016: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/27913525/checkpoint-inhibition-in-myeloma
#10
Don M Benson
Historically, attempts at cancer immunotherapy have emphasized strategies designed to stimulate or augment the immune system into action. In the past decade, a complementary approach has developed, that of releasing immune cells from inhibitory restraint. Discoveries in the fundamental biology of how immunity is regulated, how the immune system interfaces with malignancy, and how cancer cells may exploit these processes to evade detection have all been translated into the rapidly growing field of therapeutic immune checkpoint inhibition for cancer...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27912830/advances-in-small-cell-lung-cancer
#11
REVIEW
Gregory P Kalemkerian, Bryan J Schneider
Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor characterized by early metastatic spread and responsiveness to initial therapy. The incidence of SCLC has been declining in the United States in parallel with the decreasing prevalence of cigarette smoking. Limited stage disease is potentially curable with chemoradiotherapy followed by cranial irradiation. Extensive stage disease is incurable, but systemic chemotherapy can improve quality of life and prolong survival. Nearly all patients relapse with chemoresistant disease...
February 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/27912825/next-generation-sequencing-of-lung-cancers-lessons-learned-and-future-directions
#12
REVIEW
Siddhartha Devarakonda, Ashiq Masood, Ramaswamy Govindan
Targeted therapies and immune checkpoint inhibitors have significantly improved outcomes in a sizable fraction of patients with metastatic non-small cell lung cancer. Nevertheless, a majority of patients with lung cancer continue to have poor outcomes. The ability to comprehensively characterize the genomic alterations in various subtypes of lung cancer has the potential to transform cancer care by facilitating the identification of novel treatment strategies. The objective of this review is to summarize key findings from recent studies that have sequenced a large number of lung cancer samples and discuss the diagnostic, prognostic, and therapeutic relevance of these findings...
February 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/27912061/tumor-interferon-signaling-regulates-a-multigenic-resistance-program-to-immune-checkpoint-blockade
#13
Joseph L Benci, Bihui Xu, Yu Qiu, Tony J Wu, Hannah Dada, Christina Twyman-Saint Victor, Lisa Cucolo, David S M Lee, Kristen E Pauken, Alexander C Huang, Tara C Gangadhar, Ravi K Amaravadi, Lynn M Schuchter, Michael D Feldman, Hemant Ishwaran, Robert H Vonderheide, Amit Maity, E John Wherry, Andy J Minn
Therapeutic blocking of the PD1 pathway results in significant tumor responses, but resistance is common. We demonstrate that prolonged interferon signaling orchestrates PDL1-dependent and PDL1-independent resistance to immune checkpoint blockade (ICB) and to combinations such as radiation plus anti-CTLA4. Persistent type II interferon signaling allows tumors to acquire STAT1-related epigenomic changes and augments expression of interferon-stimulated genes and ligands for multiple T cell inhibitory receptors...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27910859/t-cell-programming-in-pancreatic-adenocarcinoma-a-review
#14
REVIEW
Y D Seo, V G Pillarisetty
Despite recent advancements in multimodal therapy, pancreatic ductal adenocarcinoma (PDA) continues to have a dismal prognosis. In the era of burgeoning immune therapies against previously difficult-to-treat malignancies, there has been growing interest in activating the immune system against PDA; however, unlike in other cancers such as melanoma and lymphoma, immunotherapy has not yielded many clinically significant results. To harness these mechanisms for therapeutic use, an in-depth understanding of T-cell programming in the immune microenvironment of PDA must be achieved...
December 2, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27910858/immunosuppression-in-liver-tumors-opening-the-portal-to-effective-immunotherapy
#15
REVIEW
P Guha, J Reha, S C Katz
We have recently witnessed substantial progress with immunotherapy for selected diseases. Checkpoint inhibitors and chimeric antigen receptor T (CAR-T) cells are among the most promising agents. Whereas much of the early success with CAR-T cells has been demonstrated with hematological malignancies, important barriers remain for the application of CAR-T cell therapies for the management of metastatic solid tumors. The challenges are particularly apparent when considering primary and metastatic tumors in the liver...
December 2, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27909880/il-9-producing-cells-in-the-development-of-ige-mediated-food-allergy
#16
REVIEW
Dana Shik, Sunil Tomar, Jee-Boong Lee, Chun-Yu Chen, Andrew Smith, Yui-Hsi Wang
Food allergy is a harmful immune reaction driven by uncontrolled type 2 immune responses. Considerable evidence demonstrates the key roles of mast cells, IgE, and TH2 cytokines in mediating food allergy. However, this evidence provides limited insight into why only some, rather than all, food allergic individuals are prone to develop life-threatening anaphylaxis. Clinical observations suggest that patients sensitized to food through the skin early in life may later develop severe food allergies. Aberrant epidermal thymic stromal lymphopoietin and interleukin (IL) 33 production and genetic predisposition can initiate an allergic immune response mediated by dendritic cells and CD4(+)TH2 cells in inflamed skin...
December 1, 2016: Seminars in Immunopathology
https://www.readbyqxmd.com/read/27908931/filling-the-tank-keeping-antitumor-t-cells-metabolically-fit-for-the-long-haul
#17
REVIEW
Greg M Delgoffe
Discoveries in tumor immunology and subsequent clinical advances in cancer immunotherapy have revealed that the immune system is not oblivious to tumor progression but heavily interacts with developing neoplasia and malignancy. A major factor preventing immune destruction is the establishment of a highly immunosuppressive tumor microenvironment (TME), which provides architecture to the tumor, supports indirect means of immunosuppression such as the recruitment of tolerogenic cells like regulatory T cells and myeloid-derived suppressor cells (MDSC), and represents a zone of metabolically dearth conditions...
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27908252/the-combination-of-new-immunotherapy-and-radiotherapy-a-new-potential-treatment-for-locally-advanced-non-small-cell-lung-cancer
#18
Paola Claudia Sacco, Paolo Maione, Cesare Guida, Cesare Gridelli
Lung cancer is the main reason of cancer death worldwide. About 30% of non-small-cell lung cancer (NSCLC) cases are diagnosed with locally advanced disease (stage III). This is a mixed population including patients who have far more extensive and bulky disease than others. Management of these patients continue to be a challenge; frequently, patients have both local recurrence and distant metastases in this stage and the prognosis is very poor with a 5-year overall survival estimated between 3% and 7% for inoperable disease...
December 1, 2016: Current Clinical Pharmacology
https://www.readbyqxmd.com/read/27903674/atezolizumab-a-pd-l1-blocking-antibody-for-bladder-cancer
#19
Brant A Inman, Thomas A Longo, Sundhar Ramalingam, Michael R Harrison
Atezolizumab (Tecentriq™, MPDL3280A) is an FcγR-binding deficient, fully humanized, IgG1 monoclonal antibody designed to interfere with the binding of PD-L1 ligand to its two receptors, PD-1 and B7.1. By blocking the PD-L1/PD-1 immune checkpoint, atezolizumab reduces immunosuppressive signals found within the tumor microenvironement and consequently increases T cell mediated immunity against the tumor. Atezolizumab has been FDA-approved as second-line therapy for advanced bladder cancer. This accelerated approval was based on phase 2 trial data in patients with metastatic bladder cancer that showed unexpected and durable tumor responses...
November 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27900363/integration-of-genomics-and-histology-revises-diagnosis-and-enables-effective-therapy-of-refractory-cancer-of-unknown-primary-with-pdl1-amplification
#20
Stefan Gröschel, Martin Bommer, Barbara Hutter, Jan Budczies, David Bonekamp, Christoph Heining, Peter Horak, Martina Fröhlich, Sebastian Uhrig, Daniel Hübschmann, Christina Geörg, Daniela Richter, Nicole Pfarr, Katrin Pfütze, Stephan Wolf, Peter Schirmacher, Dirk Jäger, Christof von Kalle, Benedikt Brors, Hanno Glimm, Wilko Weichert, Albrecht Stenzinger, Stefan Fröhling
Identification of the tissue of origin in cancer of unknown primary (CUP) poses a diagnostic challenge and is critical for directing site-specific therapy. Currently, clinical decision-making in patients with CUP primarily relies on histopathology and clinical features. Comprehensive molecular profiling has the potential to contribute to diagnostic categorization and, most importantly, guide CUP therapy through identification of actionable lesions. We here report the case of an advanced-stage malignancy initially mimicking poorly differentiated soft-tissue sarcoma that did not respond to multiagent chemotherapy...
November 2016: Cold Spring Harbor Molecular Case Studies
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