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Immune checkpoint inhibitor

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https://www.readbyqxmd.com/read/28934595/copd-alters-immune-cell-composition-and-immune-checkpoint-inhibitor-efficacy-in-nsclc
#1
Nicholas M Mark, Julia Kargl, Stephanie E Busch, Grace H Y Yang, Heather E Metz, Huajia Zhang, Jesse J Hubbard, Sudhakar N J Pipavath, David K Madtes, A McGarry Houghton
RATIONALE: Chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC) are interrelated diseases with substantial mortality; the pathogenesis of both involves aberrant immune functioning. OBJECTIVE: To profile the immune cell composition and function in patients with NSCLC and describe the effect of COPD on lung and tumor microenvironments. METHODS: We profiled resected lung and tumor tissue using flow cytometry and T-cell receptor sequencing in patients with and without COPD from a prospective cohort of patients undergoing resection of NSCLC...
September 21, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28932641/response-to-first-line-chemotherapy-regimen-is-associated-with-efficacy-of-nivolumab-in-non-small-cell-lung-cancer
#2
Courèche-Guillaume Kaderbhai, Corentin Richard, Jean David Fumet, Anne Aarnink, Sandra Ortiz-Cuaran, Maurice Pérol, Pascal Foucher, Bruno Coudert, Laure Favier, Aurélie Lagrange, Emeric Limagne, Romain Boidot, Sylvain Ladoire, Michel Poudenx, Marius Ilie, Paul Hofman, Pierre Saintigny, François Ghiringhelli
Nivolumab, an anti PD-1 checkpoint inhibitor has demonstrated efficacy in metastatic non-small-cell lung cancer (NSCLC) patients after failure to standard chemotherapy. Standard chemotherapy agents could promote antitumor immune response. We thus examined whether the response to first line chemotherapy could impact on nivolumab benefit. One hundred and 15 patients with NSCLC were included in this retrospective study from 4 different French centers. Forty-three squamous cell carcinomas (SCC), and 72 non-SCC received nivolumab between 2015 and 2016 (3 mg/kg IV Q2W)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28932633/cd163-positive-tumor-associated-macrophages-and-cd8-positive-cytotoxic-lymphocytes-are-powerful-diagnostic-markers-for-the-therapeutic-stratification-of-osteosarcoma-patients-an-immunohistochemical-analysis-of-the-biopsies-fromthe-french-os2006-phase-3-trial
#3
Anne Gomez-Brouchet, Claire Illac, Julia Gilhodes, Corinne Bouvier, Sébastien Aubert, Jean-Marc Guinebretiere, Béatrice Marie, Frédérique Larousserie, Natacha Entz-Werlé, Gonzague de Pinieux, Thomas Filleron, Véronique Minard, Vincent Minville, Eric Mascard, François Gouin, Marta Jimenez, Marie-Cécile Ledeley, Sophie Piperno-Neumann, Laurence Brugieres, Françoise Rédini
The French phase 3 trial (OS 2006) testing zoledronic acid, an osteoclast inhibitor, with chemotherapy and surgery did not improve the outcome of patients with osteosarcoma (OS). To understand this unexpected result, the presence of infiltrating immune cells was investigated in 124 pre-therapeutic biopsies of patients enrolled in the trial. The percentage of CD68/CD163 tumor-infiltrating macrophages (TAMs), CD8(+) lymphocytes, osteoclasts, and the PD1/PDL-1 checkpoint were assessed by immunohistochemistry. M1/M2 macrophage polarization was characterized by pSTAT1/CMAF staining...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28931759/combination-immunotherapy-with-tlr-agonists-and-checkpoint-inhibitors-suppresses-head-and-neck-cancer
#4
Fumi Sato-Kaneko, Shiyin Yao, Alast Ahmadi, Shannon S Zhang, Tadashi Hosoya, Megan M Kaneda, Judith A Varner, Minya Pu, Karen S Messer, Cristiana Guiducci, Robert L Coffman, Kazutaka Kitaura, Takaji Matsutani, Ryuji Suzuki, Dennis A Carson, Tomoko Hayashi, Ezra Ew Cohen
Checkpoint inhibitors have demonstrated efficacy in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). However, the majority of patients do not benefit from these agents. To improve the efficacy of checkpoint inhibitors, intratumoral (i.t.) injection with innate immune activators, TLR7 and TLR9 agonists, were tested along with programmed death-1 receptor (PD-1) blockade. The combination therapy suppressed tumor growth at the primary injected and distant sites in human papillomavirus-negative (HPV-negative) SCC7 and MOC1, and HPV-positive MEER syngeneic mouse models...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28931755/combination-central-tolerance-and-peripheral-checkpoint-blockade-unleashes-antimelanoma-immunity
#5
Pearl Bakhru, Meng-Lei Zhu, Hsing-Hui Wang, Lee K Hong, Imran Khan, Maria Mouchess, Ajay S Gulati, Joshua Starmer, Yafei Hou, David Sailer, Sandra Lee, Fengmin Zhao, John M Kirkwood, Stergios Moschos, Lawrence Fong, Mark S Anderson, Maureen A Su
Blockade of immune checkpoint proteins (e.g., CTLA-4, PD-1) improves overall survival in advanced melanoma; however, therapeutic benefit is limited to only a subset of patients. Because checkpoint blockade acts by "removing the brakes" on effector T cells, the efficacy of checkpoint blockade may be constrained by the limited pool of melanoma-reactive T cells in the periphery. In the thymus, autoimmune regulator (Aire) promotes deletion of T cells reactive against self-antigens that are also expressed by tumors...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28931635/a-computational-multiscale-agent-based-model-for-simulating-spatio-temporal-tumour-immune-response-to-pd1-and-pdl1-inhibition
#6
Chang Gong, Oleg Milberg, Bing Wang, Paolo Vicini, Rajesh Narwal, Lorin Roskos, Aleksander S Popel
When the immune system responds to tumour development, patterns of immune infiltrates emerge, highlighted by the expression of immune checkpoint-related molecules such as PDL1 on the surface of cancer cells. Such spatial heterogeneity carries information on intrinsic characteristics of the tumour lesion for individual patients, and thus is a potential source for biomarkers for anti-tumour therapeutics. We developed a systems biology multiscale agent-based model to capture the interactions between immune cells and cancer cells, and analysed the emergent global behaviour during tumour development and immunotherapy...
September 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28929190/mining-the-complex-family-of-protein-tyrosine-phosphatases-for-checkpoint-regulators-in-immunity
#7
Claudia Penafuerte, Luis Alberto Perez-Quintero, Valerie Vinette, Teri Hatzihristidis, Michel L Tremblay
The family of protein tyrosine phosphatases (PTPs) includes 107 genes in humans that are diverse in their structures and expression profiles. The majority are present in immune cells and play various roles in either inhibiting or promoting the duration and amplitude of signaling cascades. Several PTPs, including TC-PTP (PTPN2) and SHP-1 (PTPN6), have been recognized as being crucial for maintaining proper immune response and self-tolerance, and have gained recognition as true immune system checkpoint modulators...
September 20, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28928158/characterization-of-the-immune-microenvironment-in-hepatocellular-carcinoma-hcc
#8
Mark Yarchoan, Dongmei Xing, Lan Luan, Haiying Xu, Rajni Sharma, Aleksandra Popovic, Timothy M Pawlik, Amy K Kim, Qingfeng Zhu, Elizabeth M Jaffee, Janis Taube, Robert A Anders
PURPOSE: Hepatocellular carcinoma (HCC) often arises in the setting of chronic liver inflammation and may be responsive to novel immunotherapies. EXPERIMENTAL DESIGN: To characterize the immune microenvironment in HCC, immunohistochemical (IHC) staining was performed for CD8 positive T lymphocytes, PD-1 positive and LAG-3 positive lymphocytes, CD163 positive macrophages, and PD-L1 expression in tumor and liver background from 29 cases of resected HCC. RESULTS: Expression of CD8 was reduced in tumor and expression of CD163 was reduced at the tumor interface...
September 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28927760/interprofessional-collaboration-with-immune-checkpoint-inhibitor-therapy-the-roles-of-gastroenterology-endocrinology-and-neurology
#9
REVIEW
Virginia Seery
OBJECTIVES: To discuss immune checkpoint inhibitor therapy and identify opportunities for interprofessional collaboration in the management of toxicities in the areas of gastroenterology, endocrinology, and neurology. DATA SOURCES: Published research and education articles in oncology, nursing, and various specialties. CONCLUSION: The use of immune checkpoint inhibitors is expanding; timely management of toxicity is critical for positive patient outcomes...
September 15, 2017: Seminars in Oncology Nursing
https://www.readbyqxmd.com/read/28927079/new-use-of-microsatellite-instability-analysis-in-endometrial-cancer
#10
Haruko Kunitomi, Kouji Banno, Megumi Yanokura, Takashi Takeda, Moito Iijima, Kanako Nakamura, Miho Iida, Masataka Adachi, Keiko Watanabe, Yusuke Matoba, Yusuke Kobayashi, Eiichiro Tominaga, Daisuke Aoki
The increasing incidence of obesity and diabetes due to changes in diet, earlier menarche, delayed menopause, late marriage, and declining birth rate have resulted in an increase in the number of endometrial cancer cases over the last few decades. Although surgical therapy is sufficient for early endometrial cancer, there is no effective therapy for patients with advanced and recurrent endometrial cancer. The oncogenic mechanism of endometrial cancer involves microsatellite instability (MSI) caused by dysfunction of DNA mismatch repair genes in 30% of patients...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926891/-advances-in-immune-checkpoint-inhibitors-in-gastrointestinal-cancer
#11
X R Zhu, L Z Zheng
Currently, immunotherapy is considered as the fourth major modality of cancer treatment except surgery, chemotherapy and radiotherapy. The new therapeutic approach based on immune checkpoint inhibitors is a landmark innovation. Strategies considering checkpoint inhibitors have shown good anti-tumor effect by targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1). Moreover, DNA mismatch repair-deficient tumors appear to be potential candidates for these therapies...
September 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28926356/development-of-bell-s-palsy-after-treatment-with-ipilimumab-and-nivolumab-for-metastatic-melanoma-a-case-report
#12
Julia M Zecchini, Sara Kim, Kendra Yum, Philip Friedlander
Ipilimumab is a human monoclonal antibody that targets cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), and it is FDA approved for the treatment of unresectable or metastatic melanoma. Immune-related adverse events (irAEs) of gastrointestinal, dermatologic, and endocrine origin are commonly seen, ranging between 18% and 44%, with immune checkpoint inhibitors (anti-CTLA-4 and anti-PD-1/PD-L1). Rare irAEs include neurological, renal, and hematologic toxicities. Bell's palsy is a form of neurological toxicity that presents as an idiopathic paralysis of the muscles on one side of the face...
September 18, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28923537/metagenomic-shotgun-sequencing-and-unbiased-metabolomic-profiling-identify-specific-human-gut-microbiota-and-metabolites-associated-with-immune-checkpoint-therapy-efficacy-in-melanoma-patients
#13
Arthur E Frankel, Laura A Coughlin, Jiwoong Kim, Thomas W Froehlich, Yang Xie, Eugene P Frenkel, Andrew Y Koh
This is the first prospective study of the effects of human gut microbiota and metabolites on immune checkpoint inhibitor (ICT) response in metastatic melanoma patients. Whereas many melanoma patients exhibit profound response to ICT, there are fewer options for patients failing ICT-particularly with BRAF-wild-type disease. In preclinical studies, specific gut microbiota promotes regression of melanoma in mice. We therefore conducted a study of the effects of pretreatment gut microbiota and metabolites on ICT Response Evaluation Criteria in Solid Tumors response in 39 metastatic melanoma patients treated with ipilimumab, nivolumab, ipilimumab plus nivolumab (IN), or pembrolizumab (P)...
September 14, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28923358/targets-for-immunotherapy-of-liver-cancer
#14
REVIEW
Tim F Greten, Bruno Sangro
Drug development in HCC has been characterized in the past by many failures. Despite good rationales and promising phase II data, many phase III trials failed. Immunotherapy represents an alternate treatment approach and has been successful in many different types of cancer. Being an inflammation induced cancer HCC represents a very interesting target for immune based approaches and indeed early results from clinical trials testing immune checkpoint inhibitors are not only promising but have already led to evaluation of such in a phase III setting...
September 15, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28923104/phase-1-study-of-intravenous-administration-of-the-chimeric-adenovirus-enadenotucirev-in-patients-undergoing-primary-tumor-resection
#15
Rocio Garcia-Carbonero, Ramon Salazar, Ignacio Duran, Ignacio Osman-Garcia, Luis Paz-Ares, Juan M Bozada, Valentina Boni, Christine Blanc, Len Seymour, John Beadle, Simon Alvis, Brian Champion, Emiliano Calvo, Kerry Fisher
BACKGROUND: Enadenotucirev (formerly ColoAd1) is a tumor-selective chimeric adenovirus with demonstrated preclinical activity. This phase 1 Mechanism of Action study assessed intravenous (IV) delivery of enadenotucirev in patients with resectable colorectal cancer (CRC), non-small-cell lung cancer (NSCLC), urothelial cell cancer (UCC), and renal cell cancer (RCC) with a comparator intratumoral (IT) dosed CRC patient cohort. METHODS: Seventeen patients scheduled for primary tumor resection were enrolled...
September 19, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28922848/aggressive-behavior-in-silent-subtype-iii-pituitary-adenomas-may-depend-on-suppression-of-local-immune-response-a-whole-transcriptome-analysis
#16
Timothy E Richardson, Zhong-Jian Shen, Mohammed Kanchwala, Chao Xing, Alexander Filatenkov, Ping Shang, Samuel Barnett, Zahidur Abedin, James S Malter, Jack M Raisanen, Dennis K Burns, Charles L White, Kimmo J Hatanpaa
Silent subtype III pituitary adenomas (SS-3) are clinically nonfunctional adenomas that are more aggressive in terms of invasion and risk of recurrence than their conventional null cell counterparts. We previously showed that these tumors can be distinguished by immunohistochemistry based on the identification of a markedly enlarged and fragmented Golgi apparatus. To understand the molecular correlates of differential aggressiveness, we performed whole transcriptome sequencing (RNAseq) on 4 SS-3 and 4 conventional null cell adenomas...
October 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28921644/clinical-pharmacology-considerations-for-the-development-of-immune-checkpoint-inhibitors
#17
Jennifer Sheng, Shivani Srivastava, Kinjal Sanghavi, Zheng Lu, Brian J Schmidt, Akintunde Bello, Manish Gupta
Immuno-oncology works through activation of the patient's immune system against cancer, with several advantages over other treatment approaches, including cytotoxic agents and molecular-targeted therapies. The most notable feature of immuno-oncology treatments is the nature of the patient responses achieved, which can be more durable and sustained than with other modalities. Increased understanding of immune system complexity has provided a number of opportunities to advance several strategies for the development of immuno-oncology therapies...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28919987/programmed-death-ligand-1-pd-l1-expression-influences-the-immune-tolerogenic-microenvironment-in-antiretroviral-therapy-refractory-kaposi-s-sarcoma-a-pilot-study
#18
Salvinia Mletzko, David J Pinato, Rebecca C Robey, Alessia Dalla Pria, Peter Benson, Nesrina Imami, Mark Bower
Upregulation of programmed death ligand 1 (PD-L1) is a mechanism of immune escape utilized by a variety of tumors. PD-L1 expression in tumor cells or in the surrounding infiltrate correlates with clinical responsiveness to novel therapies targeting the PD-1/PD-L1 immune checkpoint. In the context of HIV-1 infection, Kaposi's sarcoma (KS) is largely responsive to restoration of immunity following combination antiretroviral therapy (cART), but there is a subset that is not. We hypothesized that this subset of cART-refractory KS may utilize the PD-L1 pathway of immune escape...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919706/profile-of-pembrolizumab-in-the-treatment-of-head-and-neck-squamous-cell-carcinoma-design-development-and-place-in-therapy
#19
REVIEW
Sulsal Haque, Mahender Yellu, Jaskirat Randhawa, Nooshin Hashemi-Sadraei
Head and neck squamous cell cancer (HNSCC) is the sixth most common malignancy worldwide, and despite advances in cytotoxic, surgical and radiation techniques, outcomes are still poor in those with both locally advanced and metastatic diseases. The need for development of better therapeutics along with a greater understanding of the relationship between the immune system and malignancies has led to a new therapeutic modality, immune modulators, particularly checkpoint inhibitors in HNSCC. It is now well recognized that HNSCC circumvents crucial pathways utilized by the immune system to escape surveillance...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28918995/cutaneous-adverse-events-of-targeted-therapies-for-hematolymphoid-malignancies
#20
REVIEW
Julia D Ransohoff, Bernice Y Kwong
The identification of oncogenic drivers of liquid tumors has led to the rapid development of targeted agents with distinct cutaneous adverse event (AE) profiles. The diagnosis and management of these skin toxicities has motivated a novel partnership between dermatologists and oncologists in developing supportive oncodermatology clinics. In this article we review the current state of knowledge of clinical presentation, mechanisms, and management of the most common and significant cutaneous AEs observed during treatment with targeted therapies for hematologic and lymphoid malignancies...
July 14, 2017: Clinical Lymphoma, Myeloma & Leukemia
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