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Immune checkpoint therapy

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https://www.readbyqxmd.com/read/29792730/nivolumab-for-the-treatment-of-colorectal-cancer
#1
Kortnye Maureen Smith, Jayesh Desai
Despite a variety of therapies for advanced metastatic colorectal cancer being available, the outcomes in this malignancy remain sub-optimal. Immunotherapy has been slow to impact the management of this patient group. Checkpoint inhibitors, such as nivolumab, have had disappointing results when used broadly. However, for the subset of patients with microsatellite unstable colorectal cancer the use of checkpoint inhibitors such as nivolumab appears to be transformative, and will provide a new therapeutic option for patient with advanced disease...
May 24, 2018: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/29791768/vaccine-immunotherapy-with-arnax-induces-tumor-specific-memory-t-cells-and-durable-anti-tumor-immunity-in-mouse-models
#2
Yohei Takeda, Sumito Yoshida, Ken Takashima, Noriko Ishii-Mugikura, Hiroaki Shime, Tsukasa Seya, Misako Matsumoto
Immunological checkpoint blockade therapies benefit a limited population of cancer patients. We have previously shown that vaccine immunotherapy with TLR3-adjuvant and tumor antigen overcomes anti-programmed death ligand-1 (PD-L1) resistance in mouse tumor models. In this study, four different OVA-expressing tumor cell lines were implanted into syngeneic mice and subjected to antitumor immunotherapy using ARNAX and whole OVA protein. ARNAX is a Toll-like receptor 3-specific agonist that does not activate the MAVS pathway, and thus does not induce systemic inflammation...
May 23, 2018: Cancer Science
https://www.readbyqxmd.com/read/29791021/immtac-anti-pd-1-combination-to-enhance-killing-of-cancer-cells-by-reversing-treg-mediated-immunosuppression
#3
Huanling Zhang, Yanyan Li, Xiaoping Liu, Zhaoduan Liang, Mengyong Yan, Qiang Liu, Anan Chen, Yifeng Bao, Chengzhi Zhou, Shiyue Li, Cassian Yee, Yi Li
Recently, bi-functional molecules that can redirect immune effectors to tumor cells have emerged as potentially robust mediators of tumor regression in clinical trials. Two modalities, in particular, bi-specific antibodies for T cell redirection and activation (BiTe) and immune-mobilizing monoclonal T-cell receptors against cancer (ImmTAC) are being evaluated in efficacy studies as 'off-the-shelf' reagents. Optimal therapy will require an understanding and means to address regulatory mechanisms of limiting efficacy...
May 23, 2018: Immunology
https://www.readbyqxmd.com/read/29789418/juxtacrine-signaling-inhibits-antitumor-immunity-by-upregulating-pd-l1-expression
#4
Wen-Hao Yang, Jong-Ho Cha, Weiya Xia, Heng-Huan Lee, Li-Chuan Chan, Ying-Nai Wang, Jennifer L Hsu, Guoxin Ren, Mien-Chie Hung
Programmed death-ligand 1 (PD-L1) is a well-known immune checkpoint protein that helps cancer cells evade immune response. Anti-PD-L1 immune therapy has been approved for the treatment of several advanced human cancers. Therefore, further understanding of the regulatory mechanisms of PD-L1 is critical to improve PD-L1-targeting immunotherapy. Recent studies indicated that contact-dependent pathways may regulate anticancer immunity, highlighting the importance of cell contact-induced signaling in cancer immunity...
May 22, 2018: Cancer Research
https://www.readbyqxmd.com/read/29789416/macrophage-derived-granulin-drives-resistance-to-immune-checkpoint-inhibition-in-metastatic-pancreatic-cancer
#5
Michael C Schmid, Valeria Quaranta, Carolyn Rainer, Sebastian Rune Nielsen, Meirion Llŷr Raymant, Muhammad S Ahmed, Dannielle D Engle, Arthur Taylor, Trish Murray, Fiona Campbell, Daniel H Palmer, David A Tuveson, Ainhoa Mielgo
The ability of disseminated cancer cells to evade the immune response is a critical step for efficient metastatic progression. Protection against an immune attack is often provided by the tumor microenvironment that suppresses and excludes cytotoxic CD8+ T cells. Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive metastatic disease with unmet needs, yet the immunoprotective role of the metastatic tumor microenvironment in pancreatic cancer is not completely understood. In this study we find that macrophage-derived granulin contributes to cytotoxic CD8+ T cell exclusion in metastatic livers...
May 22, 2018: Cancer Research
https://www.readbyqxmd.com/read/29787423/autoimmune-granulomatous-inflammation-of-lacrimal-glands-and-axonal-neuritis-following-treatment-with-ipilimumab-and-radiation-therapy
#6
Ecaterina Ileana Dumbrava, Veronica Smith, Rasha Alfattal, Adel K El-Naggar, Marta Penas-Prado, Apostolia M Tsimberidou
Immune checkpoint inhibitors such as anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), anti PD-1 (programmed cell death protein 1) and PD-L1 (programmed cell death protein-ligand 1) monoclonal antibodies are emerging as standard oncology treatments in various tumor types. The indications will expand as immunotherapies are being investigated in various tumors with promising results. Currently, there is inadequate identification of predictive biomarkers of response or toxicity. Unique response patterns include pseudoprogression and delayed response...
May 21, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29786170/immunopeptidomic-profiling-of-hla-a2-positive-triple-negative-breast-cancer-identifies-potential-immunotherapy-target-antigens
#7
Nicola Ternette, Marloes J M Olde Nordkamp, Julius Muller, Amanda P Anderson, Annalisa Nicastri, Adrian V S Hill, Benedikt M Kessler, Demin Li
The recent development in immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cells in the treatment of cancer has not only demonstrated the potency of utilising T-cell reactivity for cancer therapy, but has also highlighted the need for developing new approaches to discover targets suitable for such novel therapeutics. Here we analysed the immunopeptidomes of 6 HLA-A2-positive triple negative breast cancer (TNBC) samples by nano-ultra performance liquid chromatography tandem mass spectrometry (nUPLC-MS2 )...
May 22, 2018: Proteomics
https://www.readbyqxmd.com/read/29786078/targeting-the-upstream-transcriptional-activator-of-pd-l1-as-an-alternative-strategy-in-melanoma-therapy
#8
Bo Zhu, Liming Tang, Shuyang Chen, Chengqian Yin, Shiguang Peng, Xin Li, Tongzheng Liu, Wei Liu, Changpeng Han, Lukasz Stawski, Zhi-Xiang Xu, Guangbiao Zhou, Xiang Chen, Xiumei Gao, Colin R Goding, Nan Xu, Rutao Cui, Peng Cao
Programmed cell death ligand 1 (PD-L1) interacts with programmed cell death protein-1 (PD-1) as an immune checkpoint. Reactivating the immune response by inhibiting PD-L1 using therapeutic antibodies provides substantial clinical benefits in many, though not all, melanoma patients. However, transcriptional suppression of PD-L1 expression as an alternative therapeutic anti-melanoma strategy has not been exploited. Here we provide biochemical evidence demonstrating that ultraviolet radiation (UVR) induction of PD-L1 in skin is directly controlled by nuclear factor E2-related transcription factor 2 (NRF2)...
May 22, 2018: Oncogene
https://www.readbyqxmd.com/read/29785403/immunotherapy-for-hepatocellular-carcinoma-current-advances-and-future-expectations
#9
REVIEW
Yingjun Xie, Yien Xiang, Jiyao Sheng, Dan Zhang, Xiaoxiao Yao, Yongsheng Yang, Xuewen Zhang
Primary liver cancer is a common kind of digestive cancers with high malignancy, causing 745,500 deaths each year. Hepatocellular carcinoma is the major pathological type of primary liver cancer. Traditional treatment methods for patients with hepatocellular carcinoma have shown poor efficacy in killing residual cancer cells for a long time. In recent years, tumor immunotherapy has emerged as a promising method owing to its safety and efficacy with respect to delaying the progression of advanced tumors and protecting postoperative patients against tumor relapse and metastasis...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29785006/the-era-of-immunogenomics-immunopharmacogenomics
#10
REVIEW
Makda Zewde, Kazuma Kiyotani, Jae-Hyun Park, Hua Fang, Kai Lee Yap, Poh Yin Yew, Houda Alachkar, Taigo Kato, Tu H Mai, Yuji Ikeda, Tatsuo Matsuda, Xiao Liu, Lili Ren, Boya Deng, Makiko Harada, Yusuke Nakamura
Although germline alterations and somatic mutations in disease cells have been extensively analyzed, molecular changes in immune cells associated with disease conditions have not been characterized in depth. It is clear that our immune system has a critical role in various biological and pathological conditions, such as infectious diseases, autoimmune diseases, drug-induced skin and liver toxicity, food allergy, and rejection of transplanted organs. The recent development of cancer immunotherapies, particularly drugs modulating the immune checkpoint molecules, has clearly demonstrated the importance of host immune cells in cancer treatments...
May 21, 2018: Journal of Human Genetics
https://www.readbyqxmd.com/read/29784675/radiation-followed-by-ox40-stimulation-drives-local-and-abscopal-antitumor-effects-in-an-anti-pd1-resistant-lung-tumor-model
#11
Sharareh Niknam, Hampartsoum B Barsoumian, Jonathan E Schoenhals, Heather Jackson, Niranjan Yanamandra, Mauricio S Caetano, Ailin Li, Ahmed I Younes, Alexandra P Cadena, Taylor R Cushman, Joe Y Chang, Quynh Nguyen, Daniel R Gomez, Adi Diab, John V Heymach, Patrick Hwu, Maria Angelica Cortez, James W Welsh
PURPOSE: Radiation is used extensively to treat localized cancer, but improved understanding of its effects on the immune system have increased interest in its potential systemic (abscopal) effects, particularly in combination with checkpoint inhibitors such as anti-PD1. The majority of patients either do not respond or develop resistance to monotherapy over time. Here, we investigated the efficacy of OX40 (CD134) stimulation as an alternative immunotherapeutic approach in combination with radiotherapy (XRT) in a murine model of anti-PD1-resistant lung tumors...
May 21, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29782924/emerging-biomarkers-for-immune-checkpoint-inhibition-in-lung-cancer
#12
REVIEW
George Cyriac, Leena Gandhi
Immune checkpoint inhibition with anti-PD-1 therapy has been notably successful in non-small cell lung cancer (NSCLC) and changed standard practice in multiple settings. However, despite some durable benefits seen, the majority of unselected patients with NSCLC fail to respond to checkpoint inhibitors. Patient selection is crucial and will become even more important in the development of combination therapies with immune checkpoint inhibitors. PD-L1 expression by immunohistochemistry (IHC) has emerged as the most commonly used clinical biomarker of response and overall tumor mutational burden (TMB) is being explored as a clinical biomarker...
May 18, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29782188/an-evaluation-of-nivolumab-for-the-treatment-of-metastatic-renal-cell-carcinoma
#13
Kevin Zarrabi, Shenhong Wu
The treatment paradigm for metastatic renal cell carcinoma (mRCC) has undergone a revolution with the rapid market approval of multiple agents over a three-year period. The immunogenicity of RCC provided the biological rationale to assess the clinical efficacy of nivolumab, an immune checkpoint inhibitor. Nivolumab is approved for second-line treatment after failure of angiogenesis targeted therapy and in combination therapy with ipilimumab for previously untreated intermediate or poor-risk advanced renal cell carcinoma...
May 21, 2018: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29782069/efficacy-and-safety-of-nivolumab-in-non-small-cell-lung-cancer-with-preexisting-interstitial-lung-disease
#14
Osamu Kanai, Young Hak Kim, Yoshiki Demura, Makiko Kanai, Tsuyoshi Ito, Kohei Fujita, Hironori Yoshida, Masaya Akai, Tadashi Mio, Toyohiro Hirai
BACKGROUND: The risk of developing lung cancer is high in patients with interstitial lung disease (ILD), as few treatment options are available. Immune checkpoint inhibitors (ICI) are used for the treatment of non-small cell lung cancer (NSCLC) in clinical practice; however, in patients with preexisting ILD, the risk of ICI-related pneumonitis is unknown. We evaluated the efficacy and lung toxicity of nivolumab in patients with NSCLC and ILD. METHODS: We retrospectively reviewed the medical records of 216 NSCLC patients who had received nivolumab therapy...
May 21, 2018: Thoracic Cancer
https://www.readbyqxmd.com/read/29781826/understanding-microbiome-effect-on-immune-checkpoint-inhibition-in-lung-cancer-placing-the-puzzle-pieces-together
#15
Umang Swami, Yousef Zakharia, Jun Zhang
Over the past couple of years, human microbiome has received increasing attention as a regulator and predictor of response to the therapies of various diseases. It is speculated that manipulating gut microbiome can modify response to cancer immunotherapies as well. Through this review, we have critically analyzed our current understanding of gut microbiome as a modulator of immunotherapies in lung cancer, explained conflicting data, evaluated current gaps and extrapolated our present knowledge to generate directions for future investigations...
May 17, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29780635/liquid-biopsy-for-lung-cancer-early-detection
#16
REVIEW
Mariacarmela Santarpia, Alessia Liguori, Alessandro D'Aveni, Niki Karachaliou, Maria Gonzalez-Cao, Maria Grazia Daffinà, Chiara Lazzari, Giuseppe Altavilla, Rafael Rosell
Molecularly targeted therapies and immune checkpoint inhibitors have markedly improved the therapeutic management of advanced lung cancer. However, it still remains the leading cause of cancer-related mortality worldwide, with disease stage at diagnosis representing the main prognostic factor. Detection of lung cancer at an earlier stage of disease, potentially susceptible of curative resection, can be critical to improve patients survival. Low-dose computed tomography (LDCT) screening of high-risk patients has been demonstrated to reduce mortality from lung cancer, but can be also associated with high false-positive rate, thus often resulting in unnecessary interventions for patients...
April 2018: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29780381/interferon-gamma-at-the-crossroads-of-tumor-immune-surveillance-or-evasion
#17
REVIEW
Flávia Castro, Ana Patrícia Cardoso, Raquel Madeira Gonçalves, Karine Serre, Maria José Oliveira
Interferon-gamma (IFN-γ) is a pleiotropic molecule with associated antiproliferative, pro-apoptotic and antitumor mechanisms. This effector cytokine, often considered as a major effector of immunity, has been used in the treatment of several diseases, despite its adverse effects. Although broad evidence implicating IFN-γ in tumor immune surveillance, IFN-γ-based therapies undergoing clinical trials have been of limited success. In fact, recent reports suggested that it may also play a protumorigenic role, namely, through IFN-γ signaling insensitivity, downregulation of major histocompatibility complexes, and upregulation of indoleamine 2,3-dioxygenase and of checkpoint inhibitors, as programmed cell-death ligand 1...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29779086/retrospective-study-of-nivolumab-for-patients-with-recurrent-high-grade-gliomas
#18
Megan Mantica, Ashley Pritchard, Frank Lieberman, Jan Drappatz
INTRODUCTION: Patients with recurrent high-grade gliomas (HGG) have limited treatment options. HGG utilize the PD-1 pathway to evade immune responses. Checkpoint inhibitors have demonstrated safety and clinical activity in patients with recurrent glioblastoma. We explored the efficacy of nivolumab in recurrent HGG with a primary objective of progression free survival (PFS) and overall survival (OS). METHODS: We retrospectively analyzed HGG patients treated with nivolumab in our institution...
May 19, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29776373/metabolic-therapy-with-peg-arginase-induces-a-sustained-complete-remission-in-immunotherapy-resistant-melanoma
#19
Carmela De Santo, Paul Cheng, Andrew Beggs, Sharon Egan, Alberto Bessudo, Francis Mussai
BACKGROUND: Metastatic melanoma is an aggressive skin cancer with a poor prognosis. Current treatment strategies for high-stage melanoma are based around the use of immunotherapy with immune checkpoint inhibitors such as anti-PDL1 or anti-CTLA4 antibodies to stimulate anti-cancer T cell responses, yet a number of patients will relapse and die of disease. Here, we report the first sustained complete remission in a patient with metastatic melanoma who failed two immunotherapy strategies, by targeting tumour arginine metabolism...
May 18, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29775689/biomarkers-for-checkpoint-inhibition-in-hematologic-malignancies
#20
REVIEW
Djordje Atanackovic, Tim Luetkens
In the past few years we have seen remarkable paradigm shifts in the treatment of many solid tumors due to the introduction of inhibitors targeting immune checkpoints such as PD-1/PD-L1 and CTLA-4. Recent results indicate that checkpoint inhibition also represents a very promising approach for certain types of hematologic malignancies. Unfortunately, treatment with checkpoint inhibitors is also associated with substantial toxicities and high costs and only a subset of patients appears to derive clinical benefit from these treatments...
May 15, 2018: Seminars in Cancer Biology
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