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Journal for Immunotherapy of Cancer

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https://www.readbyqxmd.com/read/28105371/unfolding-anti-tumor-immunity-er-stress-responses-sculpt-tolerogenic-myeloid-cells-in-cancer
#1
REVIEW
Juan R Cubillos-Ruiz, Eslam Mohamed, Paulo C Rodriguez
Established tumors build a stressful and hostile microenvironment that blocks the development of protective innate and adaptive immune responses. Different subsets of immunoregulatory myeloid populations, including dendritic cells, myeloid-derived suppressor cells (MDSCs) and macrophages, accumulate in the stressed tumor milieu and represent a major impediment to the success of various forms of cancer immunotherapy. Specific conditions and factors within tumor masses, including hypoxia, nutrient starvation, low pH, and increased levels of free radicals, provoke a state of "endoplasmic reticulum (ER) stress" in both malignant cells and infiltrating myeloid cells...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28105370/interstitial-nephritis-in-melanoma-patients-secondary-to-pd-1-checkpoint-inhibitor
#2
Julia Escandon, Stephanie Peacock, Asaad Trabolsi, David B Thomas, Ayman Layka, Jose Lutzky
BACKGROUND: Immune checkpoint inhibitors have become the first line therapy in melanoma treatment and their use is extending to other malignancies. However, we are still learning about immune side effects produced by these drugs and their severity especially in patients with history of inflammatory diseases. CASE PRESENTATION: We present two cases of metastatic melanoma treated with nivolumab and pembrolizumab (anti PD-1). Both patients developed acute interstitial nephritis during immune checkpoint therapy...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28105369/potassium-channels-of-t-lymphocytes-take-center-stage-in-the-fight-against-cancer
#3
EDITORIAL
Laura Conforti
A recent study by Eil at al. published in Nature in September 2016 provides evidence that alterations of the K(+) homeostasis of tumor infiltrating lymphocytes (TILs) in necrotic areas of the tumor microenvironment (TME) suppress the function of effector T cells. Furthermore, they establish that overexpression of K(+) channels in T lymphocytes counterbalances this negative effect of the TME and restores the ability of TILs to function, ultimately leading to increased survival of tumor bearing mice. Thus, K(+) channels in T lymphocytes become interesting new targets for novel immunotherapies in cancer...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28105368/clinical-and-immunologic-correlates-of-response-to-pd-1-blockade-in-a-patient-with-metastatic-renal-medullary-carcinoma
#4
Kathryn E Beckermann, Pradeep C Jolly, Ju Y Kim, Jennifer Bordeaux, Igor Puzanov, W Kimryn Rathmell, Douglas B Johnson
BACKGROUND: Renal medullary carcinoma (RMC) is a rare kidney tumor that occurs in adolescent and young adults, typically in association with sickle cell trait. RMC exhibits rapid disease progression, frequent metastases at diagnosis, and dismal clinical outcomes. Currently available therapies, including cisplatin-based combination chemotherapy, multi-tyrosine kinase, and mTOR inhibitor strategies demonstrate either transient responses or minimal activity. Therefore, further molecular characterization and additional treatment strategies are urgently needed in this aggressive disease...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28031824/canine-cancer-immunotherapy-studies-linking-mouse-and-human
#5
REVIEW
Jiwon S Park, Sita S Withers, Jaime F Modiano, Michael S Kent, Mingyi Chen, Jesus I Luna, William T N Culp, Ellen E Sparger, Robert B Rebhun, Arta M Monjazeb, William J Murphy, Robert J Canter
Despite recent major clinical breakthroughs in human cancer immunotherapy including the use of checkpoint inhibitors and engineered T cells, important challenges remain, including determining the sub-populations of patients who will respond and who will experience at times significant toxicities. Although advances in cancer immunotherapy depend on preclinical testing, the majority of in-vivo testing currently relies on genetically identical inbred mouse models which, while offering critical insights regarding efficacy and mechanism of action, also vastly underrepresent the heterogeneity and complex interplay of human immune cells and cancers...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28031823/challenges-and-opportunities%C3%A2-for-checkpoint-blockade-in-t-cell-lymphoproliferative-disorders
#6
REVIEW
Tycel Phillips, Sumana Devata, Ryan A Wilcox
The T-cell lymphoproliferative disorders are a heterogeneous group of non-Hodgkin's lymphomas (NHL) for which current therapeutic strategies are inadequate, as most patients afflicted with these NHL will succumb to disease progression within 2 years of diagnosis. Appreciation of the genetic and immunologic landscape of these aggressive NHL, including PD-L1 (B7-H1, CD274) expression by malignant T cells and within the tumor microenvironment, provides a strong rationale for therapeutic targeting this immune checkpoint...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28031822/sarcoidosis-in-the-setting-of-combination-ipilimumab-and-nivolumab-immunotherapy-a-case-report-review-of-the-literature
#7
Joshua E Reuss, Paul R Kunk, Anne M Stowman, Alejandro A Gru, Craig L Slingluff, Elizabeth M Gaughan
BACKGROUND: We report a case of sarcoidosis in a patient with metastatic melanoma managed with combination ipilimumab/nivolumab. Sarcoid development has been linked with single agent immunotherapy but, to our knowledge, it has not been reported with combination ipilimumab/nivolumab treatment. This case raises unique management challenges for both the melanoma and the immunotherapy-related toxicity. CASE PRESENTATION: A 46 year old Caucasian female with M1c-metastatic melanoma was managed with ipilimumab/nivolumab combination...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28031821/advances-in-immunotherapeutic-strategies-for-colorectal-cancer-commentary-on-tumoral-immune-cell-exploitation-in-colorectal-cancer-metastases-can-be-targeted-effectively-by-anti-ccr5-therapy-in-cancer-patients-by-halama-et-al
#8
EDITORIAL
Dustin A Deming
Colorectal cancer is a leading cause of cancer-related death in the United States, despite recent advances in treatment strategies. The immune system has been implicated in the pathogenesis of colorectal cancer, with numerous studies identifying either antagonistic or pro-tumorigenic effects of infiltrating immune cells. Therapeutic strategies harnessing the immune system to target cancers have evolved expediently over the last 5 years, especially the use of checkpoint inhibitors. Recently, a subset of patients whose colorectal cancers harbor a deficiency in mismatch repair proteins have demonstrated dramatic and durable response to checkpoint blockade...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28031820/the-society-for-immunotherapy-of-cancer-consensus-statement-on-immunotherapy-for-the-treatment-of-prostate-carcinoma
#9
Douglas G McNeel, Neil H Bander, Tomasz M Beer, Charles G Drake, Lawrence Fong, Stacey Harrelson, Philip W Kantoff, Ravi A Madan, William K Oh, David J Peace, Daniel P Petrylak, Hank Porterfield, Oliver Sartor, Neal D Shore, Susan F Slovin, Mark N Stein, Johannes Vieweg, James L Gulley
Prostate cancer is the most commonly diagnosed malignancy and second leading cause of cancer death among men in the United States. In recent years, several new agents, including cancer immunotherapies, have been approved or are currently being investigated in late-stage clinical trials for the management of advanced prostate cancer. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel, including physicians, nurses, and patient advocates, to develop consensus recommendations for the clinical application of immunotherapy for prostate cancer patients...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28031819/genetic-risk-analysis-of-a-patient-with-fulminant-autoimmune-type-1-diabetes-mellitus-secondary-to-combination-ipilimumab-and-nivolumab-immunotherapy
#10
Jared R Lowe, Daniel J Perry, April K S Salama, Clayton E Mathews, Larry G Moss, Brent A Hanks
BACKGROUND: Checkpoint inhibitor immunotherapy is becoming an effective treatment modality for an increasing number of malignancies. As a result, autoinflammatory side-effects are also being observed more commonly in the clinic. We are currently unable to predict which patients will develop more severe toxicities associated with these treatment regimens. CASE PRESENTATION: We present a patient with stage IV melanoma that developed rapid onset autoimmune type 1 diabetes (T1D) in response to combination ipilimumab and nivolumab immunotherapy...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28031818/being-penny-wise-but-pound-foolish-in-cancer-immunotherapy-research-the-urgent-need-for-mouse-cancer-models-to-reflect-human-modifying-factors
#11
EDITORIAL
William J Murphy
Inbred mice are the mainstay for preclinical cancer assessment of potential therapeutics, especially immune-based approaches. However, the use of young, lean, inbred mice housed under specific-pathogen-free conditions does not mirror the human cancer scenario. This commentary discusses some of the issues in evaluating immunotherapeutics in mice given recent advances.
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28031817/a-new-vista-on-combination-therapy-for-negative-checkpoint-regulator-blockade
#12
REVIEW
Jie Deng, Isabelle Le Mercier, Anna Kuta, Randolph J Noelle
Negative checkpoint regulators function to restrain T cell responses to maintain tolerance and limit immunopathology. However, in the setting of malignancy, these pathways work in concert to promote immune-mediate escape leading to the development of a clinically overt cancer. In the recent years, clinical trials demonstrating the efficacy of blocking antibodies against these molecules have invigorated the field of immunotherapy. In this review, we discuss the current understanding on established NCR blockade and how strategic combination therapy with anti-VISTA antibody can be used to target multiple non-redundant NCR pathways...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28031816/a-phase-ib-study-of-ipilimumab-with-peginterferon-alfa-2b-in-patients-with-unresectable-melanoma
#13
Andrew S Brohl, Nikhil I Khushalani, Zeynep Eroglu, Joseph Markowitz, Ram Thapa, Y Ann Chen, Ragini Kudchadkar, Jeffrey S Weber
BACKGROUND: Ipilimumab and peginterferon alfa-2b are established systemic treatment options for melanoma that have distinct mechanisms of action. Given the need for improved therapies for advanced melanoma, we conducted an open-label, single institution, phase Ib study to assess the safety and tolerability of using these two agents in combination. METHODS: Study treatment consisted of ipilimumab given every 3 weeks, for a total of four infusions, concurrent with peginterferon alfa-2b administered subcutaneous weekly for a total of 12 weeks...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28018602/fusion-of-the-dendritic-cell-targeting-chemokine-mip3%C3%AE-to-melanoma-antigen-gp100-in-a-therapeutic-dna-vaccine-significantly-enhances-immunogenicity-and-survival-in-a-mouse-melanoma-model
#14
James T Gordy, Kun Luo, Hong Zhang, Arya Biragyn, Richard B Markham
BACKGROUND: Although therapeutic cancer vaccines have been mostly disappointing in the clinic, the advent of novel immunotherapies and the future promise of neoantigen-based therapies have created the need for new vaccine modalities that can easily adapt to current and future developments in cancer immunotherapy. One such novel platform is a DNA vaccine fusing the chemokine Macrophage Inflammatory Protein-3α (MIP-3α) to an antigen, here melanoma antigen gp100. Previous published work has indicated that MIP-3α targets nascent peptides to immature dendritic cells, leading to processing by class I and II MHC pathways...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28018601/the-society-for-immunotherapy-of-cancer-consensus-statement-on-immunotherapy-for-the-treatment-of-hematologic-malignancies-multiple-myeloma-lymphoma-and-acute-leukemia
#15
Michael Boyiadzis, Michael R Bishop, Rafat Abonour, Kenneth C Anderson, Stephen M Ansell, David Avigan, Lisa Barbarotta, Austin John Barrett, Koen Van Besien, P Leif Bergsagel, Ivan Borrello, Joshua Brody, Jill Brufsky, Mitchell Cairo, Ajai Chari, Adam Cohen, Jorge Cortes, Stephen J Forman, Jonathan W Friedberg, Ephraim J Fuchs, Steven D Gore, Sundar Jagannath, Brad S Kahl, Justin Kline, James N Kochenderfer, Larry W Kwak, Ronald Levy, Marcos de Lima, Mark R Litzow, Anuj Mahindra, Jeffrey Miller, Nikhil C Munshi, Robert Z Orlowski, John M Pagel, David L Porter, Stephen J Russell, Karl Schwartz, Margaret A Shipp, David Siegel, Richard M Stone, Martin S Tallman, John M Timmerman, Frits Van Rhee, Edmund K Waller, Ann Welsh, Michael Werner, Peter H Wiernik, Madhav V Dhodapkar
Increasing knowledge concerning the biology of hematologic malignancies as well as the role of the immune system in the control of these diseases has led to the development and approval of immunotherapies that are resulting in impressive clinical responses. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a hematologic malignancy Cancer Immunotherapy Guidelines panel consisting of physicians, nurses, patient advocates, and patients to develop consensus recommendations for the clinical application of immunotherapy for patients with multiple myeloma, lymphoma, and acute leukemia...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28018600/a-quantum-leap-in-cancer-vaccines
#16
EDITORIAL
Eli Gilboa
No abstract text is available yet for this article.
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28018599/immune-related-response-assessment-during-pd-1-inhibitor-therapy-in-advanced-non-small-cell-lung-cancer-patients
#17
Mizuki Nishino, Nikhil H Ramaiya, Emily S Chambers, Anika E Adeni, Hiroto Hatabu, Pasi A Jänne, F Stephen Hodi, Mark M Awad
BACKGROUND: Tumor response characteristics using immune-related RECIST1.1 (irRECIST1.1) in advanced non-small-cell lung cancer (NSCLC) patients treated with nivolumab monotherapy in the clinical setting have not been previously described with a direct comparison with the assessments according to the conventional RECIST1.1. METHODS: Fifty-six advanced NSCLC patients treated with nivolumab monotherapy after its Food and Drug Administration (FDA) approval were retrospectively studied...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27895920/pd1-pd-l1-inhibition-as-a-potential-radiosensitizer-in-head-and-neck-squamous-cell-carcinoma-a-case-report
#18
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
#19
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
#20
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
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