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Cancer Immunology, Immunotherapy: CII

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https://www.readbyqxmd.com/read/28444424/the-experience-of-immune-checkpoint-inhibitors-in-chinese-patients-with-metastatic-melanoma-a-retrospective-case-series
#1
Xizhi Wen, Ya Ding, Jingjing Li, Jingjing Zhao, Ruiqing Peng, Dandan Li, Baoyan Zhu, Yao Wang, Xing Zhang, Xiaoshi Zhang
Melanomas in Chinese patients show relatively higher rates of acral and mucosal types than in other populations. However, the efficacy of checkpoint inhibitor therapies against these melanoma subtypes is not well defined. We analyzed 52 patients treated with ipilimumab, pembrolizumab, or a combination of both to evaluate the efficacy and safety of checkpoint inhibitors in Chinese patients with advanced melanoma, particularly those with acral and mucosal types. The objective response rates (ORRs) were 0, 25, and 20% for ipilimumab, pembrolizumab, and pembrolizumab plus ipilimumab, respectively...
April 25, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28434031/fkbp51s-signature-in-peripheral-blood-mononuclear-cells-of-melanoma-patients-as-a-possible-predictive-factor-for-immunotherapy
#2
Simona Romano, Ester Simeone, Anna D'Angelillo, Paolo D'Arrigo, Michele Russo, Mario Capasso, Vito Alessandro Lasorsa, Nicola Zambrano, Paolo A Ascierto, Maria Fiammetta Romano
The inhibitory immune checkpoint PD-L1/PD1 promotes the alternative splicing of the FKBP5 gene, resulting in increased expression of its variant 4 in the peripheral blood mononuclear cells of melanoma patients. The variant 4 transcript is translated into the truncated FKBP51s protein. Given the importance of co-inhibitory signalling in tumour immune escape, here we tested the potential for using FKBP51s expression to predict immunotherapy outcomes. To do this, we immunophenotyped PBMCs from 118 melanoma patients and 77 age- and sex-matched healthy controls...
April 22, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28432397/downregulation-of-neuropilin-1-on-macrophages-modulates-antibody-mediated-tumoricidal-activity
#3
Kosuke Kawaguchi, Eiji Suzuki, Mariko Nishie, Isao Kii, Tatsuki R Kataoka, Masahiro Hirata, Masashi Inoue, Fengling Pu, Keiko Iwaisako, Moe Tsuda, Ayane Yamaguchi, Hironori Haga, Masatoshi Hagiwara, Masakazu Toi
Neuropilin-1 (NRP-1)-expressing macrophages are engaged in antitumor immune functions via various mechanisms. In this study, we investigated the role of NRP-1 on macrophages in antibody-mediated tumoricidal activity. Treatment of macrophages with NRP-1 knockdown or an anti-NRP-1-neutralizing antibody significantly suppressed antibody-dependent cellular cytotoxicity and modulated cytokine secretion from macrophages in vitro. Furthermore, in vivo studies using a humanized mouse model bearing human epidermal growth factor receptor-2 (HER2)-positive breast cancer xenografts showed that antibody-mediated antitumor activity and tumor infiltration of CD4(+) T lymphocytes were significantly downregulated when peripheral blood mononuclear cells in which NRP-1 was knocked down were co-administered with an anti-HER2 antibody...
April 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28429069/mupexi-prediction-of-neo-epitopes-from-tumor-sequencing-data
#4
Anne-Mette Bjerregaard, Morten Nielsen, Sine Reker Hadrup, Zoltan Szallasi, Aron Charles Eklund
Personalization of immunotherapies such as cancer vaccines and adoptive T cell therapy depends on identification of patient-specific neo-epitopes that can be specifically targeted. MuPeXI, the mutant peptide extractor and informer, is a program to identify tumor-specific peptides and assess their potential to be neo-epitopes. The program input is a file with somatic mutation calls, a list of HLA types, and optionally a gene expression profile. The output is a table with all tumor-specific peptides derived from nucleotide substitutions, insertions, and deletions, along with comprehensive annotation, including HLA binding and similarity to normal peptides...
April 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28409192/can-local-radiotherapy-and-il-12-synergise-to-overcome-the-immunosuppressive-tumor-microenvironment-and-allow-in-situ-tumor-vaccination
#5
Gaël Deplanque, Keyvan Shabafrouz, Michel Obeid
The abscopal effect, which is the spontaneous regression of tumors or metastases outside the radiation field, occurs rarely in cancer patients. Interestingly, radiotherapy (RT) triggers an immunogenic cell death (ICD) that is able to generate tumor-specific cytotoxic CD8(+) T cells that are efficient in killing cancer cells. The key question is: why is this "abscopal effect" so uncommon in cancer patients treated with RT? Most probably, the main reason may be related to the highly immunosuppressive tumor microenvironment of well-established tumors that constantly antagonizes the anti-tumor immune responses triggered by RT...
April 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28409191/the-summit-for-cancer-immunotherapy-summit4ci-june-26-29-2016-halifax-canada
#6
Maartje C A Wouters, Céline M Laumont, Branson Chen, Seong Jun Han, Kathy Matuszewska, Kyle Potts, Jeanette E Boudreau, Connie M Krawczyk
No abstract text is available yet for this article.
April 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28405765/coexpressed-modular-gene-expression-reveals-inverse-correlation-between-immune-responsive-transcription-and-aggressiveness-in-gastric-tumours
#7
Kalaivani Kalamohan, Dhanasekaran Rathinam, Ponmathi Panneerpandian, Kumaresan Ganesan
The existing large number of gene expression profiles of tumour samples offers a great advantage for the integrative functional genomic exploration of molecular dysregulation in cancers. The clusters of genes (modules) derived from a gastric cancer (GC) coexpression network were explored to understand their clinical and functional significance. Among the modules derived from the GC mRNA expression network, six modules were relatively highly expressed in diffuse type gastric tumours. Elevated expression of genes related to extracellular matrix (ECM), angiogenesis, collagen and intracellular cytoskeletal components and immune response were identified in these modules...
April 12, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28405764/prognostic-implication-of-cd274-pd-l1-protein-expression-in-tumor-infiltrating-immune-cells-for-microsatellite-unstable-and-stable-colorectal-cancer
#8
Kyu Sang Lee, Yoonjin Kwak, Soyeon Ahn, Eun Shin, Heung-Kwon Oh, Duck-Woo Kim, Sung-Bum Kang, Gheeyoung Choe, Woo Ho Kim, Hye Seung Lee
In this study, we investigated the clinical relevance of CD274 (PD-L1) protein expression by tumor cells and tumor-infiltrating immune cells in colorectal cancer (CRC). To this end, 186 microsatellite instability-high (MSI-H) and 153 microsatellite stable (MSS) CRCs were subjected to immunohistochemistry (IHC) analysis for the expression of CD274 and mismatch repair proteins. CD274 expression was evaluated in tumor cells at the center (TC) and periphery (TP), and immune cells at the center (IC) and periphery (IP) of CRC...
April 12, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28401258/tumor-associated-myeloid-cells-as-guiding-forces-of-cancer-cell-stemness
#9
REVIEW
Antonio Sica, Chiara Porta, Alberto Amadori, Anna Pastò
Due to their ability to differentiate into various cell types and to support tissue regeneration, stem cells simultaneously became the holy grail of regenerative medicine and the evil obstacle in cancer therapy. Several studies have investigated niche-related conditions that favor stemness properties and increasingly emphasized their association with an inflammatory environment. Tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) are major orchestrators of cancer-related inflammation, able to dynamically express different polarized inflammatory programs that promote tumor outgrowth, including tumor angiogenesis, immunosuppression, tissue remodeling and metastasis formation...
April 11, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28401257/ido-and-galectin-3-hamper-the-ex-vivo-generation-of-clinical-grade-tumor-specific-t-cells-for-adoptive-cell-therapy-in-metastatic-melanoma
#10
Sara M Melief, Marten Visser, Sjoerd H van der Burg, Els M E Verdegaal
Adoptive T cell transfer (ACT) with ex vivo-expanded tumor-reactive T cells proved to be successful for the treatment of metastatic melanoma patients. Mixed lymphocyte tumor cell cultures (MLTC) can be used to generate tumor-specific T cells for ACT; however, in a number of cases tumor-reactive T cell, expansion is far from optimal. We hypothesized that this is due to tumor intrinsic and extrinsic factors and aimed to identify and manipulate these factors so to optimize our clinical, GMP-compliant MLTC protocol...
April 11, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28391358/genetic-evolution-of-uveal-melanoma-guides-the-development-of-an-inflammatory-microenvironment
#11
Gülçin Gezgin, Mehmet Dogrusöz, T Huibertus van Essen, Wilhelmina G M Kroes, Gregorius P M Luyten, Pieter A van der Velden, Vonn Walter, Robert M Verdijk, Thorbald van Hall, Sjoerd H van der Burg, Martine J Jager
Uveal melanoma (UM) is characterized by a number of genetic aberrations that follow a certain chronology and are tightly linked to tumor recurrence and survival. Loss of chromosome 3, bi-allelic loss of BAP1 expression, and gain in chromosome 8q have been associated with metastasis formation and death, while loss of chromosome 3 has been associated with the influx of macrophages and T cells. We used a set of genetically-classified UM to study immune infiltration in the context of their genetic evolution. We show in two independent cohorts that lack of BAP1 expression is associated with an increased density of CD3(+) T cells and CD8(+) T cells...
April 8, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28391357/phase-i-iia-clinical-trial-of-a-novel-htert-peptide-vaccine-in-men-with-metastatic-hormone-naive-prostate-cancer
#12
Wolfgang Lilleby, Gustav Gaudernack, Paal F Brunsvig, Ljiljana Vlatkovic, Melanie Schulz, Kate Mills, Knut Håkon Hole, Else Marit Inderberg
In newly diagnosed metastatic hormone-naive prostate cancer (mPC), telomerase-based immunotherapy with the novel hTERT peptide vaccine UV1 can induce immune responses with potential clinical benefit. This phase I dose escalation study of UV1 evaluated safety, immune response, effects on prostate-specific antigen (PSA) levels, and preliminary clinical outcome. Twenty-two patients with newly diagnosed metastatic hormone-naïve PC (mPC) were enrolled; all had started androgen deprivation therapy and had no visceral metastases...
April 8, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28382399/ccr5-in-recruitment-and-activation-of-myeloid-derived-suppressor-cells-in-melanoma
#13
REVIEW
Viktor Umansky, Carolin Blattner, Christoffer Gebhardt, Jochen Utikal
Malignant melanoma is characterized by the development of chronic inflammation in the tumor microenvironment, leading to the accumulation of myeloid-derived suppressor cells (MDSCs). Using ret transgenic mouse melanoma model, we found a significant migration of MDSCs expressing C-C chemokine receptor (CCR)5 into primary tumors and metastatic lymph nodes, which was correlated with tumor progression. An increased CCR5 expression on MDSCs was associated with elevated concentrations of CCR5 ligands in melanoma microenvironment...
April 5, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28378067/bone-marrow-myeloid-cells-in-regulation-of-multiple-myeloma-progression
#14
REVIEW
Sarah E Herlihy, Cindy Lin, Yulia Nefedova
Survival, growth, and response to chemotherapy of cancer cells depends strongly on the interaction of cancer cells with the tumor microenvironment. In multiple myeloma, a cancer of plasma cells that localizes preferentially in the bone marrow, the microenvironment is highly enriched with myeloid cells. The majority of myeloid cells are represented by mature and immature neutrophils. The contribution of the different myeloid cell populations to tumor progression and chemoresistance in multiple myeloma is discussed...
April 4, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28361232/cancer-immunotherapy-how-low-level-ionizing-radiation-can-play-a-key-role
#15
REVIEW
Marek K Janiak, Marta Wincenciak, Aneta Cheda, Ewa M Nowosielska, Edward J Calabrese
The cancer immunoediting hypothesis assumes that the immune system guards the host against the incipient cancer, but also "edits" the immunogenicity of surviving neoplastic cells and supports remodeling of tumor microenvironment towards an immunosuppressive and pro-neoplastic state. Local irradiation of tumors during standard radiotherapy, by killing neoplastic cells and generating inflammation, stimulates anti-cancer immunity and/or partially reverses cancer-promoting immunosuppression. These effects are induced by moderate (0...
March 30, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28349165/programmed-death-ligand-1-and-its-soluble-form-are-highly-expressed-in-nasal-natural-killer-t-cell-lymphoma-a-potential-rationale-for-immunotherapy
#16
Toshihiro Nagato, Takayuki Ohkuri, Kenzo Ohara, Yui Hirata, Kan Kishibe, Yuki Komabayashi, Seigo Ueda, Miki Takahara, Takumi Kumai, Kei Ishibashi, Akemi Kosaka, Naoko Aoki, Kensuke Oikawa, Yuji Uno, Naoko Akiyama, Masatoshi Sado, Hidehiro Takei, Esteban Celis, Yasuaki Harabuchi, Hiroya Kobayashi
Nasal natural killer/T-cell lymphoma (NNKTL) is an aggressive neoplasm with poor therapeutic responses and prognosis. The programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) pathway plays an important role in immune evasion of tumor cells through T-cell exhaustion. The aim of the present study was to examine the expression of PD-L1 and PD-1 molecules in NNKTL. We detected the expression of PD-L1 in biopsy samples from all of the NNKTL patients studied. PD-L1 was found on both malignant cells and tumor-infiltrating macrophages, while PD-1-positive mononuclear cells infiltrated the tumor tissues in 36% of patients...
March 27, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28341875/pd-l1-overexpression-is-partially-regulated-by-egfr-her2-signaling-and-associated-with-poor-prognosis-in-patients-with-non-small-cell-lung-cancer
#17
Riki Okita, Ai Maeda, Katsuhiko Shimizu, Yuji Nojima, Shinsuke Saisho, Masao Nakata
Immunocheckpoint inhibitors targeting the programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1) axis have shown promising results in patients with non-small-cell lung cancer (NSCLC). Recent research has shown that epidermal growth factor receptor (EGFR) signaling affects PD-L1 expression in NSCLC cells; however, the mechanism regulating PD-L1 expression in tumor cells remains unclear. Using immunohistochemistry, we evaluated the impact of expression of PD-L1 and EGF family receptors EGFR and human epidermal growth factor receptor 2 (HER2) in tumor cells from 91 patients with pathological Stage IA-IIIA NSCLC...
March 25, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28341874/the-multi-faceted-potential-of-cd38-antibody-targeting-in-multiple-myeloma
#18
Rory M Shallis, Christopher M Terry, Seah H Lim
CD38, an adenine dinucleotide phosphate (ADP) ribose cyclase and a cyclic ADP ribose hydrolase, is widely expressed on the surface of multiple myeloma (MM) cells. It is known to play a pivotal role in the downstream pathways that mediate MM cell growth, signal transduction, and adhesion. The clinical use of CD38 monoclonal antibodies (MoAbs), such as daratumumab, either as monotherapy or in combination with other anti-MM agents, has produced impressive results in patients who have failed standard MM therapy...
March 24, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28324125/exercise-and-cancer-from-healthy-to-therapeutic
#19
REVIEW
Manja Idorn, Per Thor Straten
Exercise improves functional capacity and patient-reported outcomes across a range of cancer diagnoses. The mechanisms behind this protection have been largely unknown, but exercise-mediated changes in body composition, sex hormone levels, systemic inflammation, and immune cell function have been suggested to play a role. We recently demonstrated that voluntary exercise leads to an influx of immune cells in tumors, and a more than 60% reduction in tumor incidence and growth across several mouse models. Given the common mechanisms of immune cell mobilization in mouse and man during exercise, we hypothesize that this link between exercise and the immune system can be exploited in cancer therapy in particular in combination with immunotherapy...
March 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28321480/a-new-peptide-vaccine-ocv-501-in-vitro-pharmacology-and-phase-1-study-in-patients-with-acute-myeloid-leukemia
#20
Yukio Kobayashi, Toru Sakura, Shuichi Miyawaki, Kazuyuki Toga, Shinji Sogo, Yuji Heike
Wilms' tumor 1 (WT1) is a promising target of new immunotherapies for acute myeloid leukemia (AML) as well as for other cancers. OCV-501 is a helper peptide derived from the WT1 protein. OCV-501 induced OCV-501-specific Type 1 T-helper (Th1) responses dose-dependently and stimulated helper activity of the specific Th1 cells in peripheral blood mononuclear cells from healthy donors. OCV-501 also enhanced the increase in WT1-killer peptide-specific cytotoxic T lymphocytes. OCV-501 stimulated the OCV-501-specific Th1 clones in an HLA class-II restricted manner and formed a complex with HLA class-II protein...
March 20, 2017: Cancer Immunology, Immunotherapy: CII
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