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Journal for Immunotherapy of Cancer

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https://www.readbyqxmd.com/read/27895920/pd1-pd-l1-inhibition-as-a-potential-radiosensitizer-in-head-and-neck-squamous-cell-carcinoma-a-case-report
#1
Misako Nagasaka, Mark Zaki, Harold Kim, S Naweed Raza, George Yoo, Ho-Sheng Lin, Ammar Sukari
BACKGROUND: Immunotherapy targeting the checkpoint PD1 (programmed cell death protein 1) or PDL1 (programmed death ligand 1) has led to advances in the treatment of melanoma and non-small cell lung cancer (NSCLC). The use of such therapies has also been introduced into the treatment of other malignancies, including head and neck cancer. The combined effects of checkpoint inhibitors and anti-PD1(L1) antibodies and radiation therapy have not yet been sufficiently investigated. CASE PRESENTATION: We report a case of locally relapsed non-resectable oral cavity squamous cell carcinoma, with excellent local control after pembrolizumab (MK3475) followed by radiotherapy...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27895919/recurrent-pleural-effusions-and-cardiac-tamponade-as-possible-manifestations-of-pseudoprogression-associated-with-nivolumab-therapy-a-report-of-two-cases
#2
Bhaskar C Kolla, Manish R Patel
BACKGROUND: Checkpoint inhibitors are a class of agents that employ host's adaptive immune defenses in fighting cancer. With many new indications and several ongoing clinical trials in a variety of malignancies, the usage of these agents is set to increase significantly. One of the key challenges patients and physicians face while using these drugs is with the appropriate assessment of response to therapy. CASE PRESENTATION: We are reporting two patients with lung cancer who were treated with nivolumab and experienced rapidly accumulating recurrent pleural effusions requiring multiple thoracenteses (6 and 4 times each for patient 1 and 2 respectively) with in the first few weeks of initiation of therapy and also developed pericardial effusion with cardiac tamponade requiring pericardiocentesis...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27895918/classical-and-non-classical-hla-class-i-aberrations-in-primary-cervical-squamous-and-adenocarcinomas-and-paired-lymph-node-metastases
#3
Debbie M Ferns, A Marijne Heeren, Sanne Samuels, Maaike C G Bleeker, Tanja D de Gruijl, Gemma G Kenter, Ekaterina S Jordanova
BACKGROUND: Tumors avoid destruction by cytotoxic T cells (CTL) and natural killer (NK) cells by downregulation of classical human leukocyte antigens (HLA) and overexpression of non-classical HLA. This is the first study to investigate HLA expression in relation to histology (squamous cell carcinoma (SCC) vs. adenocarcinoma (AC)), clinicopathological parameters and survival in a large cervical cancer patient cohort. METHODS: Classical (HLA-A and HLA-B/C)- and non-classical HLA molecules (HLA-E and HLA-G) were studied on primary tumors and paired lymph node (LN) metastases from cervical cancer patients (n = 136) by immunohistochemistry...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27895917/validation-of-biomarkers-to-predict-response-to-immunotherapy-in-cancer-volume-i-pre-analytical-and-analytical-validation
#4
REVIEW
Giuseppe V Masucci, Alessandra Cesano, Rachael Hawtin, Sylvia Janetzki, Jenny Zhang, Ilan Kirsch, Kevin K Dobbin, John Alvarez, Paul B Robbins, Senthamil R Selvan, Howard Z Streicher, Lisa H Butterfield, Magdalena Thurin
Immunotherapies have emerged as one of the most promising approaches to treat patients with cancer. Recently, there have been many clinical successes using checkpoint receptor blockade, including T cell inhibitory receptors such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death-1 (PD-1). Despite demonstrated successes in a variety of malignancies, responses only typically occur in a minority of patients in any given histology. Additionally, treatment is associated with inflammatory toxicity and high cost...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27891227/society-for-immunotherapy-of-cancer-consensus-statement-on-immunotherapy-for-the-treatment-of-renal-cell-carcinoma
#5
Brian I Rini, David F McDermott, Hans Hammers, William Bro, Ronald M Bukowski, Bernard Faba, Jo Faba, Robert A Figlin, Thomas Hutson, Eric Jonasch, Richard W Joseph, Bradley C Leibovich, Thomas Olencki, Allan J Pantuck, David I Quinn, Virginia Seery, Martin H Voss, Christopher G Wood, Laura S Wood, Michael B Atkins
Immunotherapy has produced durable clinical benefit in patients with metastatic renal cell cancer (RCC). In the past, patients treated with interferon-alpha (IFN) and interleukin-2 (IL-2) have achieved complete responses, many of which have lasted for multiple decades. More recently, a large number of new agents have been approved for RCC, several of which attack tumor angiogenesis by inhibiting vascular endothelial growth factors (VEGF) and VEGF receptors (VEGFR), as well as tumor metabolism, inhibiting the mammalian target of rapamycin (mTOR)...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27891226/validation-of-biomarkers-to-predict-response-to-immunotherapy-in-cancer-volume-ii-clinical-validation-and-regulatory-considerations
#6
REVIEW
Kevin K Dobbin, Alessandra Cesano, John Alvarez, Rachael Hawtin, Sylvia Janetzki, Ilan Kirsch, Giuseppe V Masucci, Paul B Robbins, Senthamil R Selvan, Howard Z Streicher, Jenny Zhang, Lisa H Butterfield, Magdalena Thurin
There is growing recognition that immunotherapy is likely to significantly improve health outcomes for cancer patients in the coming years. Currently, while a subset of patients experience substantial clinical benefit in response to different immunotherapeutic approaches, the majority of patients do not but are still exposed to the significant drug toxicities. Therefore, a growing need for the development and clinical use of predictive biomarkers exists in the field of cancer immunotherapy. Predictive cancer biomarkers can be used to identify the patients who are or who are not likely to derive benefit from specific therapeutic approaches...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27891225/unraveling-the-role-of-preexisting-immunity-in-prostate-cancer-patients-vaccinated-with-a-her-2-neu-hybrid-peptide
#7
Ioannis F Voutsas, Eleftheria A Anastasopoulou, Panagiotis Tzonis, Michael Papamichail, Sonia A Perez, Constantin N Baxevanis
BACKGROUND: Cancer vaccines aim at eliciting not only an immune response against specific tumor antigens, but also at enhancing a preexisting immunity against the tumor. In this context, we recently reported on the levels of preexisting immunity in prostate cancer patients vaccinated with the HER-2 hybrid peptide (AE37), during a phase I clinical trial. The purpose of the current study was to correlate between preexisting immunity to the native HER-2 peptide, AE36, and expression of HLA-A2 and -A24 molecules with the clinical outcome...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27879975/metastatic-merkel-cell-carcinoma-response-to-nivolumab
#8
Frances M Walocko, Benjamin Y Scheier, Paul W Harms, Leslie A Fecher, Christopher D Lao
BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine malignancy with limited treatment options. Several lines of evidence support the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) axis as a likely contributor to immune evasion in MCC. CASE PRESENTATION: We report a case of a patient with metastatic MCC with a significant and durable response to nivolumab, a humanized IgG4 monoclonal anti-PD-1 antibody. CONCLUSION: Immunotherapy with PD-1/PD-L1 inhibitors has become a rational and promising treatment option for MCC in the advanced or metastatic disease...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27879974/nivolumab-dose-selection-challenges-opportunities-and-lessons-learned-for-cancer-immunotherapy
#9
Shruti Agrawal, Yan Feng, Amit Roy, Georgia Kollia, Brian Lestini
BACKGROUND: Immuno-oncology (I-O) therapies target the host immune system, providing the potential to choose a uniform dose and schedule across tumor types. However, dose selection for I-O agents usually occurs early in clinical development and is typically based on tumor response, which may not fully represent the potential for improved overall survival. Here, we describe an integrated approach which incorporates clinical safety and efficacy data with data obtained from analyses of dose-/exposure-response (D-R/E-R) relationships, used to select a monotherapy dose for nivolumab, a programmed death-1 inhibitor, in clinical studies of different tumor types...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27879973/application-of-the-immunoscore-as-prognostic-tool-for-hepatocellular-carcinoma
#10
EDITORIAL
Annacarmen Petrizzo, Luigi Buonaguro
To date, the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC) tumor, nodes, metastasis (TNM) classification represents the standard system for evaluation of prognosis in solid tumors. However, the clinical outcome can be significantly different in patients with the same TNM stage. Therefore, many efforts have been made aiming to define new prognostic parameters. Indeed, analyses conducted in large cohorts of colorectal cancer patients emphasized the prognostic value of tumor-infiltrating lymphocytes, leading to the development of a prognostic score referred to as "Immunoscore"...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27879972/responses-of-metastatic-basal-cell-and-cutaneous-squamous-cell-carcinomas-to-anti-pd1-monoclonal-antibody-regn2810
#11
Gerald S Falchook, Rom Leidner, Elizabeth Stankevich, Brian Piening, Carlo Bifulco, Israel Lowy, Matthew G Fury
BACKGROUND: Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (CSCC) share exposure to UV light as the dominant risk factor, and these tumors therefore harbor high mutation burdens. In other malignancies, high mutation burden has been associated with clinical benefit from therapy with antibodies directed against the Programmed Death 1 (PD-1) immune checkpoint receptor. Highly mutated tumors are more likely to express immunogenic tumor neoantigens that attract effector T cells, which can be unleashed by blockade of the PD-1 immune checkpoint...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27879971/tcr-diversity-a-universal-cancer-immunotherapy-biomarker
#12
EDITORIAL
Douglas G McNeel
Sipuleucel-T was approved as a treatment for men with advanced metastatic, castration-resistant prostate cancer on the basis of improved survival in randomized clinical trials. A major challenge for this therapy, as well as other newer cancer immunotherapy agents, has been to identify markers that can identify patients who benefit from these therapies. In a recent manuscript by Sheikh and colleagues, the investigators evaluated changes in T cell clonality in the peripheral blood and tumors of patients treated with sipuleucel-T using next generation sequencing of T cell receptor Vß CDR3 sequences...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27822377/erratum-to-agonist-anti-gitr-monoclonal-antibody-and-stereotactic-radiation-induce-immune-mediated-survival-advantage-in-murine-intracranial-glioma
#13
Mira A Patel, Jennifer E Kim, Debebe Theodros, Ada Tam, Esteban Velarde, Christina M Kochel, Brian Francica, Thomas R Nirschl, Ali Ghasemzadeh, Dimitrios Mathios, Sarah Harris-Bookman, Christopher C Jackson, Christina Jackson, Xiaobu Ye, Phuoc T Tran, Betty Tyler, Vladimir Coric, Mark Selby, Henry Brem, Charles G Drake, Drew M Pardoll, Michael Lim
[This corrects the article DOI: 10.1186/s40425-016-0132-2.].
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27777777/anti-pd-1-increases-the-clonality-and-activity-of-tumor-infiltrating-antigen-specific-t-cells-induced-by-a-potent-immune-therapy-consisting-of-vaccine-and-metronomic-cyclophosphamide
#14
Genevieve M Weir, Olga Hrytsenko, Tara Quinton, Neil L Berinstein, Marianne M Stanford, Marc Mansour
BACKGROUND: Future cancer immunotherapies will combine multiple treatments to generate functional immune responses to cancer antigens through synergistic, multi-modal mechanisms. In this study we explored the combination of three distinct immunotherapies: a class I restricted peptide-based cancer vaccine, metronomic cyclophosphamide (mCPA) and anti-PD-1 treatment in a murine tumor model expressing HPV16 E7 (C3). METHODS: Mice were implanted with C3 tumors subcutaneously...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27777776/high-dose-interleukin2-a-10-year-single-site-experience-in-the-treatment-of-metastatic-renal-cell-carcinoma-careful-selection-of-patients-gives-an-excellent-outcome
#15
S Chow, V Galvis, M Pillai, R Leach, E Keene, A Spencer-Shaw, A Shablak, J Shanks, T Liptrot, F Thistlethwaite, R E Hawkins
BACKGROUND: VEGF-targeted therapy has become the mainstay of treatment for majority of mRCC patients. For most patients, benefit is short-lived and therefore treatment remains palliative in intent. HD IL2 is an effective immunotherapy treatment capable of durable remission in some patients but its unselected use has been difficult due to its modest response rate and considerable adverse effects. Using set pathology criteria as a selection tool in clinical practice, we have been able to show improved outcomes in our previous report...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27777775/acute-visual-loss-after-ipilimumab-treatment-for-metastatic-melanoma
#16
Melissa A Wilson, Kelly Guld, Steven Galetta, Ryan D Walsh, Julia Kharlip, Madhura Tamhankar, Suzanne McGettigan, Lynn M Schuchter, Leslie A Fecher
BACKGROUND: Ipilimumab, a humanized CLTA-4 antibody is a standard therapy in the treatment of advanced melanoma. While ipilimumab provides an overall survival benefit to patients, it can be associated with immune related adverse events (IrAEs). CASE PRESENTATION: Here we describe a patient treated with ipilimumab who experienced known IrAEs, including hypophysitis, as well as a profound vision loss due to optic neuritis. There are rare reports of optic neuritis occurring as an adverse event associated with ipilimumab treatment...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27777774/5-fluorouracil-upregulates-cell-surface-b7-h1-pd-l1-expression-in-gastrointestinal-cancers
#17
Lauren Van Der Kraak, Gaurav Goel, Krishnaveni Ramanan, Christof Kaltenmeier, Lin Zhang, Daniel P Normolle, Gordon J Freeman, Daolin Tang, Katie S Nason, Jon M Davison, James D Luketich, Rajeev Dhupar, Michael T Lotze
BACKGROUND: Resistance to chemotherapy is a major obstacle in the effective treatment of cancer patients. B7-homolog 1, also known as programmed death ligand-1 (PD-L1), is an immunoregulatory protein that is overexpressed in several human cancers. Interaction of B7-H1 with programmed death 1 (PD-1) prevents T-cell activation and proliferation, sequestering the T-cell receptor from the cell membrane, inducing T-cell apoptosis, thereby leading to cancer immunoresistance. B7-H1 upregulation contributes to chemoresistance in several types of cancer, but little is known with respect to changes associated with 5-fluorouracil (5-FU) or gastrointestinal cancers...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27777773/antitumor-activity-of-nivolumab-on-hemodialysis-after-renal-allograft-rejection
#18
Michael Ong, Andrea Marie Ibrahim, Samuel Bourassa-Blanchette, Christina Canil, Todd Fairhead, Greg Knoll
BACKGROUND: Nivolumab (Opdivo™) is a novel IgG4 subclass programmed death-1 (PD-1) inhibiting antibody that has demonstrated breakthrough-designation anti-tumor activity. To date, clinical trials of nivolumab and other checkpoint inhibitors have generally excluded patients with solid organ transplantation and patients with concurrent immunosuppression. However, organ transplant recipients are at high-risk of development of malignancy as a result of suppressed immune surveillance of cancer...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27777772/urothelial-carcinoma-of-donor-origin-in-a-kidney-transplant-patient
#19
Rosa M Michel Ortega, Daynna J Wolff, Cynthia A Schandl, Harry A Drabkin
BACKGROUND: Malignancy after transplantation is an uncommon multifactorial occurrence. Immunosuppression to prevent graft rejection is described as a major risk factor in malignancy development in the post-transplant state. Donor-derived malignancy is a rare reported complication. Herein, we review our patient history and discuss diagnostic strategies and the implications of immunosuppression for donor-derived malignancy. CASE PRESENTATION: This is a 69-year-old man with post-renal-transplant urothelial carcinoma determined to be of donor origin...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27777771/expansion-of-tumor-infiltrating-lymphocytes-til-from-human-pancreatic-tumors
#20
MacLean Hall, Hao Liu, Mokenge Malafa, Barbara Centeno, Pamela J Hodul, José Pimiento, Shari Pilon-Thomas, Amod A Sarnaik
BACKGROUND: We evaluated whether tumor infiltrating lymphocytes (TIL) could be expanded from surgically resected tumors from pancreatic cancer patients. METHODS: Tumors were resected from pancreatic cancer patients. Tumors were minced into fragments and cultured in media containing high dose interleukin-2 (IL-2) for up to 6 weeks. T cell phenotype, activation markers, and reactivity were measured. RESULTS: TIL expansion was measured in 19 patient samples...
2016: Journal for Immunotherapy of Cancer
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