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immune-checkpoint blockade

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https://www.readbyqxmd.com/read/29441437/immune-checkpoint-blockade-the-new-frontier-in-cancer-treatment
#1
Jeffrey M Clarke, Daniel J George, Stacey Lisi, April K S Salama
Immune checkpoint blockers have revolutionized cancer treatment in recent years. These agents are now approved for the treatment of several malignancies, including melanoma, squamous and non-squamous non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, and head and neck squamous cell carcinoma. Studies have demonstrated the significant impact of immunotherapy versus standard of care on patient outcomes, including durable response and extended survival. The use of immunotherapy-based combination therapy has been shown to further extend duration of response and survival...
February 13, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29439955/dual-pd1-lag3-immune-checkpoint-blockade-limits-tumor-development-in-a-murine-model-of-chronic-lymphocytic-leukemia
#2
Marina Wierz, Sandrine Pierson, Léa Guyonnet, Elodie Viry, Audrey Lequeux, Anaïs Oudin, Simone P Niclou, Markus Ollert, Guy Berchem, Bassam Janji, Coralie Guérin, Jerome Paggetti, Etienne Moussay
No abstract text is available yet for this article.
February 13, 2018: Blood
https://www.readbyqxmd.com/read/29439670/phase-i-study-of-an-active-immunotherapy-for-asymptomatic-phase-lymphoplasmacytic-lymphoma-with-dna-vaccines-encoding-antigen-chemokine-fusion-study-protocol
#3
Sheeba K Thomas, Soung-Chul Cha, D Lynne Smith, Kun Hwa Kim, Sapna R Parshottam, Sheetal Rao, Michael Popescu, Vincent Y Lee, Sattva S Neelapu, Larry W Kwak
BACKGROUND: There is now a renewed interest in cancer vaccines. Patients responding to immune checkpoint blockade usually bear tumors that are heavily infiltrated by T cells and express a high load of neoantigens, indicating that the immune system is involved in the therapeutic effect of these agents; this finding strongly supports the use of cancer vaccine strategies. Lymphoplasmacytic lymphoma (LPL) is a low grade, incurable disease featuring an abnormal proliferation of Immunoglobulin (Ig)-producing malignant cells...
February 13, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29437767/t-cell-exhaustion-signatures-vary-with-tumor-type-and-are-severe-in-glioblastoma
#4
Karolina Woroniecka, Pakawat Chongsathidkiet, Kristen E Rhodin, Hanna R Kemeny, Cosette A Dechant, Samuel H Farber, Aladine A Elsamadicy, Xiuyu Cui, Shohei Koyama, Christina C Jackson, Landon J Hansen, Tanner M Johanns, Luis Sanchez-Perez, Vidyalakshmi Chandramohan, Yen-Rei A Yu, Darell D Bigner, Amber J Giles, Patrick Healy, Glenn Dranoff, Kent J Weinhold, Gavin P Dunn, Peter E Fecci
PURPOSE: T cell dysfunction is a hallmark of GBM. While anergy and tolerance have been well characterized, T cell exhaustion remains relatively unexplored. Exhaustion, characterized in part by the upregulation of multiple immune checkpoints, is a known contributor to failures amidst immune checkpoint blockade, a strategy that has lacked success thus far in GBM. This study is among the first to examine, and credential as bona fide, exhaustion among T cells infiltrating human and murine GBM...
February 7, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29436396/rapid-activation-of-tumor-associated-macrophages-boosts-preexisting-tumor-immunity
#5
Sabine Hoves, Chia-Huey Ooi, Carsten Wolter, Hadassah Sade, Stefan Bissinger, Martina Schmittnaegel, Oliver Ast, Anna M Giusti, Katharina Wartha, Valeria Runza, Wei Xu, Yvonne Kienast, Michael A Cannarile, Hyam Levitsky, Solange Romagnoli, Michele De Palma, Dominik Rüttinger, Carola H Ries
Depletion of immunosuppressive tumor-associated macrophages (TAMs) or reprogramming toward a proinflammatory activation state represent different strategies to therapeutically target this abundant myeloid population. In this study, we report that inhibition of colony-stimulating factor-1 receptor (CSF-1R) signaling sensitizes TAMs to profound and rapid reprogramming in the presence of a CD40 agonist before their depletion. Despite the short-lived nature of macrophage hyperactivation, combined CSF-1R+CD40 stimulation of macrophages is sufficient to create a proinflammatory tumor milieu that reinvigorates an effective T cell response in transplanted tumors that are either responsive or insensitive to immune checkpoint blockade...
February 7, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29435295/identification-of-candidate-responders-for-anti-pd-l1-pd-1-immunotherapy-rova-t-therapy-or-ezh2-inhibitory-therapy-in-small-cell-lung-cancer
#6
Motonobu Saito, Katsuharu Saito, Kouya Shiraishi, Daichi Maeda, Hiroyuki Suzuki, Yoshihiro Minamiya, Koji Kono, Takashi Kohno, Akiteru Goto
A useful candidate for small-cell lung cancer (SCLC) therapy is immune checkpoint blockade therapy targeting programmed death-1 (PD-1) and its ligand, PD-L1. Furthermore, rovalpituzumab tesirine (Rova-T), a delta-like protein 3 (DLL3)-targeted antibody-drug conjugate, and enhancer of zeste homologue 2 (EZH2) inhibitor are expected to be the first targeted therapy for SCLC. The aim of the present study was to evaluate PD-L1, DLL3 and EZH2 expression in SCLCs to find a candidate responder to those therapies. Immunohistochemical (IHC) staining for PD-L1, DLL3 and EZH2 was performed in 20 patients with SCLC and the clinicopathological characteristics and IHC staining intensity were compared...
February 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29431745/dkk2-imparts-tumor-immunity-evasion-through-%C3%AE-catenin-independent-suppression-of-cytotoxic-immune-cell-activation
#7
Qian Xiao, Jibo Wu, Wei-Jia Wang, Shiyang Chen, Yingxia Zheng, Xiaoqing Yu, Katrina Meeth, Mahnaz Sahraei, Alfred L M Bothwell, Lieping Chen, Marcus Bosenberg, Jianfeng Chen, Veronika Sexl, Le Sun, Lin Li, Wenwen Tang, Dianqing Wu
Immunotherapy offers new options for cancer treatment, but efficacy varies across cancer types. Colorectal cancers (CRCs) are largely refractory to immune-checkpoint blockade, which suggests the presence of yet uncharacterized immune-suppressive mechanisms. Here we report that the loss of adenomatosis polyposis coli (APC) in intestinal tumor cells or of the tumor suppressor PTEN in melanoma cells upregulates the expression of Dickkopf-related protein 2 (DKK2), which, together with its receptor LRP5, provides an unconventional mechanism for tumor immune evasion...
February 12, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29431673/a-critical-need-for-better-cancer-immunotherapy-models-are-organotypic-tumor-spheroid-cultures-the-answer
#8
Justin M Balko, Jeffrey A Sosman
Immunotherapy has transformed the therapeutic landscape of cancer, but the preclinical evaluation of combination approaches that will deepen and broaden its clinical benefit has lagged far behind due to the lack of expedient and easily accessible ex vivo human systems. In this issue, Jenkins and colleagues and Deng and colleagues report the use of organotypic cultures of tumors derived from mice and humans containing both tumor cells and cells from their local immune microenvironment to recapitulate the in vivo use of immune checkpoint inhibitors and extend the application of this system to therapeutic combinations of immune checkpoint blockade and molecularly targeted agents...
February 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29424936/checkpoint-inhibitors-in-triple-negative-breast-cancer-tnbc-where-to-go-from-here
#9
REVIEW
Maryann J Kwa, Sylvia Adams
Advances in cancer immunotherapy and a growing body of research have focused on the role of the antitumor response in breast cancer. Triple-negative breast cancer (TNBC) is the most immunogenic breast cancer subtype, and there is strong evidence that tumor-infiltrating lymphocytes in TNBC have prognostic value and are associated with clinical outcome and improved survival. Evading antitumor immunity is a hallmark for the development and progression of cancer. Immunotherapy studies have focused on the role of the programmed cell death-1 (PD-1) receptor/programmed death-ligand 1 (PD-L1) pathway in maintaining immunosuppression in the tumor microenvironment...
February 9, 2018: Cancer
https://www.readbyqxmd.com/read/29423649/pretreatment-neutrophil-to-lymphocyte-ratio-is-associated-with-outcome-of-advanced-stage-cancer-patients-treated-with-immunotherapy-a-meta-analysis
#10
Tao Jiang, Meng Qiao, Chao Zhao, Xuefei Li, Guanghui Gao, Chunxia Su, Shengxiang Ren, Caicun Zhou
BACKGROUND: To investigate the association between pretreatment blood neutrophil-to-lymphocyte ratio (NLR) and clinical outcomes for advanced-stage cancer patients treated with immunotherapy. METHODS: We conducted a comprehensive literature search to assess the relationship between pretreatment blood NLR and overall survival (OS) or progression-free survival (PFS) in advanced-stage cancer patients treated with immunotherapy. Published data including hazard ratios (HRs) and related 95% confidence interval (CI) were extracted...
February 8, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29409495/pd-1-axis-expression-in-musculoskeletal-tumors-and-antitumor-effect-of-nivolumab-in-osteosarcoma-model-of-humanized-mouse
#11
Bingxin Zheng, Tingting Ren, Yi Huang, Kunkun Sun, Shidong Wang, Xing Bao, Kuisheng Liu, Wei Guo
BACKGROUND: Immune checkpoint inhibitors have led to a breakthrough in solid tumor immunotherapy, but related studies on musculoskeletal tumors are few, especially for PD-L2. METHODS: We examined expression of three molecular effectors of the PD-1 axis in 234 patients with musculoskeletal tumors, including osteosarcoma, chondrosarcoma, synovial sarcoma, and giant cell tumor. Survival analyses and potential mechanisms were investigated in osteosarcoma per the Gene Expression Omnibus (GEO) and immunohistochemistry analyses...
February 6, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29404522/distinct-clinical-and-magnetic-resonance-features-of-metastatic-hepatocellular-carcinoma-treated-with-pembrolizumab-a-case-report-of-late-response-after-pseudoprogression
#12
Patrick Grierson, Danielle Crites, Marianna B Ruzinova, Motoyo Yano, Kian-Huat Lim
There are few effective therapies for unresectable or metastatic hepatocellular carcinoma. Recent data have demonstrated efficacy of immune checkpoint blockade in this difficult to treat disease; however, clinical experience is limited. We report a case of hepatocellular carcinoma displaying pseudoprogression followed by a late response with novel magnetic resonance imaging features following treatment with the anti-programmed cell death protein 1 agent pembrolizumab. (Hepatology Communications 2018;2:148-151)...
February 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29399410/poly-i-c-primes-primary-human-glioblastoma-cells-for-an-immune-response-invigorated-by-pd-l1-blockade
#13
Jorrit De Waele, Elly Marcq, Jonas Rm Van Audenaerde, Jinthe Van Loenhout, Christophe Deben, Karen Zwaenepoel, Erik Van de Kelft, David Van der Planken, Tomas Menovsky, Johan Mj Van den Bergh, Yannick Willemen, Patrick Pauwels, Zwi N Berneman, Filip Lardon, Marc Peeters, An Wouters, Evelien Lj Smits
Prognosis of glioblastoma remains dismal, underscoring the need for novel therapies. Immunotherapy is generating promising results, but requires combination strategies to unlock its full potential. We investigated the immunomodulatory capacities of poly(I:C) on primary human glioblastoma cells and its combinatorial potential with programmed death ligand (PD-L) blockade. In our experiments, poly(I:C) stimulated expression of both PD-L1 and PD-L2 on glioblastoma cells, and a pro-inflammatory secretome, including type I interferons (IFN) and chemokines CXCL9, CXCL10, CCL4 and CCL5...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399407/beta-blocker-use-correlates-with-better-overall-survival-in-metastatic-melanoma-patients-and-improves-the-efficacy-of-immunotherapies-in-mice
#14
Kathleen M Kokolus, Ying Zhang, Jeffrey M Sivik, Carla Schmeck, Junjia Zhu, Elizabeth A Repasky, Joseph J Drabick, Todd D Schell
Immunotherapy has expanded treatment options for cancers with historically poor outcomes, yet a significant proportion of patients still fail to achieve durable clinical benefit. We defined the contribution of β-adrenergic receptor (βAR) signaling, a component of the stress response, on success of immunotherapy for melanoma since the use of antagonists (β-blockers) is associated with improved clinical outcomes in some cancers. We show that metastatic melanoma patients who received immunotherapy had improved overall survival if they also received pan β-blockers...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399401/a-safe-and-highly-efficient-tumor-targeted-type-i-interferon-immunotherapy-depends-on-the-tumor-microenvironment
#15
Anje Cauwels, Sandra Van Lint, Geneviève Garcin, Jennyfer Bultinck, Franciane Paul, Sarah Gerlo, José Van der Heyden, Yann Bordat, Dominiek Catteeuw, Lode De Cauwer, Elke Rogge, Annick Verhee, Gilles Uzé, Jan Tavernier
Despite approval for the treatment of various malignancies, clinical application of cytokines such as type I interferon (IFN) is severely impeded by their systemic toxicity. AcTakines (Activity-on-Target cytokines) are optimized immunocytokines that, when injected in mice, only reveal their activity upon cell-specific impact. We here show that type I IFN-derived AcTaferon targeted to the tumor displays strong antitumor activity without any associated toxicity, in contrast with wild type IFN. Treatment with CD20-targeted AcTaferon of CD20+ lymphoma tumors or melanoma tumors engineered to be CD20+, drastically reduced tumor growth...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399393/pd-1-blockade-reverses-adaptive-immune-resistance-induced-by-high-dose-hypofractionated-but-not-low-dose-daily-fractionated-radiation
#16
Megan Morisada, Paul E Clavijo, Ellen Moore, Lillian Sun, Michael Chamberlin, Carter Van Waes, James W Hodge, James B Mitchell, Jay Friedman, Clint T Allen
Preclinical evidence suggests that high-dose hypofractionated ionizing radiation (IR) can enhance anti-tumor immunity and result in significant tumor control when combined with immune checkpoint blockade (ICB). However, low-dose daily fractioned IR used for many tumor types including head and neck squamous cell carcinoma results in lymphopenia and may be immunosuppressive. We compared immune correlates, primary tumor and abscopal tumor control rates following the addition of PD-1 mAb to either high-dose hypofractioned (8Gyx2) or low-dose daily fractionated (2Gyx10) IR in syngeneic models of cancer...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399391/dendritic-cell-vaccine-induces-antigen-specific-cd8-t-cells-that-are-metabolically-distinct-from-those-of-peptide-vaccine-and-is-well-combined-with-pd-1-checkpoint-blockade
#17
Koji Nagaoka, Akihiro Hosoi, Tamaki Iino, Yasuyuki Morishita, Hirokazu Matsushita, Kazuhiro Kakimi
The success of immune checkpoint blockade has unequivocally demonstrated that anti-tumor immunity plays a pivotal role in cancer therapy. Because endogenous tumor-specific T-cell responsiveness is essential for the success of checkpoint blockade, combination therapy with cancer vaccination may facilitate tumor rejection. To select the best vaccine strategy to combine with checkpoint blockade, we compared dendritic cell-based vaccines (DC-V) with peptide vaccines for induction of anti-tumor immunity that could overcome tumor-induced immunosuppression...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399387/analysis-of-pd1-pdl1-pdl2-expression-and-t-cells-infiltration-in-1014-gastric-cancer-patients
#18
Xiaofang Xing, Jianping Guo, Xianzi Wen, Guangyu Ding, Bo Li, Bin Dong, Qin Feng, Shen Li, Jian Zhang, Xiaojing Cheng, Ting Guo, Hong Du, Ying Hu, Xiaohong Wang, Lin Li, Qingda Li, Meng Xie, Liting Li, Xiangyu Gao, Fei Shan, Ziyu Li, Xiaomin Ying, Tao Zhou, Jiping Wang, Jiafu Ji
Although immune checkpoint blockade have demonstrated promising results, their effects on gastric cancer (GC) are under investigation. Understanding the clinical significance of PD1 and its ligands' expression, together with T cell infiltration might provide clues for biomarkers screening in GC immunotherapy. Immunohistochemistry were performed on a tissue microarray including 1,014 GC specimens using PD1, PDL1 and PDL2 antibodies. T cell markers CD3 and CD8 were also stained and quantified by automated image analysis...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29398572/enhanced-antitumor-efficacy-through-microwave-ablation-in-combination-with-immune-checkpoints-blockade-in-breast-cancer-a-pre-clinical-study-in-a-murine-model
#19
J Zhu, M Yu, L Chen, P Kong, L Li, G Ma, H Ge, Y Cui, Z Li, H Pan, H Xie, W Zhou, S Wang
PURPOSE: The purpose of this study was to investigate the therapeutic efficacy of the combination of microwave ablation (MWA) in combination with immune checkpoints blockade in the treatment of breast cancer using the 4T1 tumor-bearing mice model. MATERIALS AND METHODS: We treated tumor-bearing mice with MWA, programmed cell death protein1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blockade (P+C), MWA plus PD-1 and CTLA-4 blockade (combination therapy), or no-treatment...
February 1, 2018: Diagnostic and Interventional Imaging
https://www.readbyqxmd.com/read/29396703/immunologic-milieu-of-mature-t-cell-and-nk-cell-lymphomas-implications-for-therapy
#20
REVIEW
Eric Tse, Yok-Lam Kwong
PURPOSE OF THE REVIEW: T-cells and natural killer (NK) cells share the same ontogeny, and lymphomas derived from them are clinically diverse, occurring in nodal and extranodal sites. In addition to inherent properties of these lymphomas, their microenvironment also impacts on pathogenesis and response to therapy. An understanding of the milieu of T-cell and NK cell lymphomas has important implications on treatment. RECENT FINDINGS: Components of the microenvironment include tumour-associated macrophages (TAM), non-neoplastic T-cells and B-cells, eosinophils, dendritic cells, endothelial cells and blood vessels...
February 2, 2018: Current Hematologic Malignancy Reports
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