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Tumor immunotherapy

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https://www.readbyqxmd.com/read/29050282/effective-antitumor-peptide-vaccines-can-induce-severe-autoimmune-pathology
#1
Hussein Sultan, Jimena Trillo-Tinoco, Paulo Rodriguez, Esteban Celis
Immunotherapy has shown a tremendous success in treating cancer. Unfortunately, this success is frequently associated with severe autoimmune pathology. In this study, we used the transgenic RIP-gp mouse model to assess the antitumor therapeutic benefit of peptide vaccination while evaluating the possible associated autoimmune pathology. We report that palmitoylated gp33-41 peptide and poly-IC adjuvant vaccine (BiVax) generated ∼ 5-10 % of antigen specific T cell responses in wild type and supposedly immune tolerant RIP-gp mice...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050165/-ovarian-tumor-associated-with-anti-n-methyl-d-aspartate-receptor-encephalitis-a-report-of-15-cases
#2
X M Li, H Y Jiang, Y F Wang, W Qiu, Y Wang, H T Wu
Objective: To summarize the clinical features of patients with ovarian tumor and anti-N-methyl-D-aspartate receptor(NMDAR) encephalitis, and to explore the influence of operation patterns on the prognosis. Methods: The clinical information of patients with ovarian tumor and anti-NMDAR encephalitis in The 3rd Affiliated Hospital of Sun Yat-Sen University and The Zhujiang Hospital of Southern Medical University were collected and analyzed. Results: There were 15 patients were enrolled in this study, with the average age of 24...
October 10, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29048978/antitumor-effect-of-oral-cancer-vaccine-with-bifidobacterium-delivering-wt1-protein-to-gut-immune-system-is-superior-to-wt1-peptide-vaccine
#3
Toshiro Shirakawa, Koichi Kitagawa
Despite the revolutionary progress of immune checkpoint inhibitors (CPIs) for cancer immunotherapy, CPIs are effective only in a subset of patients. Combining CPIs and cancer vaccines to achieve better clinical outcomes is a reasonable approach since CPI enhances cancer vaccine-induced tumor-associated antigen (TAA) specific CTL. Among the various TAAs so far identified, WT1 protein is one of the most promising TAAs as a cancer vaccine target. Until now clinical trials of WT1 vaccine have demonstrated only modest clinical efficacy...
October 19, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29048671/adoptive-immunotherapy-combined-with-fp-treatment-for-head-and-neck-cancer-an-in%C3%A2-vitro-study
#4
Mayako Nishio-Nagai, Susumu Suzuki, Kazuhiro Yoshikawa, Ryuzo Ueda, Yoshiaki Kazaoka
FP treatment, which combines 5-fluorouracil (5-FU) and cisplatin (CDDP) chemotherapy, is widely used for treatment of advanced head and neck cancer (HNC). It has been suggested that these drugs cause immunomodulation in the cancer microenvironment, for example, downregulation of immunosuppressive cells such as regulatory T-cells (Tregs) and myeloid-derived suppressive cells (MDSCs), activating dendritic cells (DCs), and upregulation of tumor antigens and major histocompatibility complex (MHC) molecules in cancer cells leads to enhancement of cancer immunity, which is important in cancer treatment, as well as providing a direct killing effect...
October 2, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29046675/interpreting-t-cell-cross-reactivity-through-structure-implications-for-tcr-based-cancer-immunotherapy
#5
Dinler A Antunes, Maurício M Rigo, Martiela V Freitas, Marcus F A Mendes, Marialva Sinigaglia, Gregory Lizée, Lydia E Kavraki, Liisa K Selin, Markus Cornberg, Gustavo F Vieira
Immunotherapy has become one of the most promising avenues for cancer treatment, making use of the patient's own immune system to eliminate cancer cells. Clinical trials with T-cell-based immunotherapies have shown dramatic tumor regressions, being effective in multiple cancer types and for many different patients. Unfortunately, this progress was tempered by reports of serious (even fatal) side effects. Such therapies rely on the use of cytotoxic T-cell lymphocytes, an essential part of the adaptive immune system...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29046389/the-antibody-repertoire-of-colorectal-cancer
#6
Seong Won Cha, Stefano Bonissone, Seungjin Na, Pavel A Pevzner, Vineet Bafna
Immunotherapy is becoming increasingly important in the fight against cancers, utilizing and manipulating the body's immune response to treat tumors. Understanding the immune repertoire - the collection of immunological proteins - of treated and untreated cells is possible at the genomic, but technically difficult at the protein level. Standard protein databases do not include the highly divergent sequences of somatic rearranged immunoglobulin genes, and may lead to missed identifications in a mass spectrometry search...
October 18, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29045907/reactive-neutrophil-responses-dependent-on-the-receptor-tyrosine-kinase-c-met-limit-cancer-immunotherapy
#7
Nicole Glodde, Tobias Bald, Debby van den Boorn-Konijnenberg, Kyohei Nakamura, Jake S O'Donnell, Sabrina Szczepanski, Maria Brandes, Sarah Eickhoff, Indrajit Das, Naveen Shridhar, Daniel Hinze, Meri Rogava, Tetje C van der Sluis, Janne J Ruotsalainen, Evelyn Gaffal, Jennifer Landsberg, Kerstin U Ludwig, Christoph Wilhelm, Monika Riek-Burchardt, Andreas J Müller, Christoffer Gebhardt, Richard A Scolyer, Georgina V Long, Viktor Janzen, Michele W L Teng, Wolfgang Kastenmüller, Massimiliano Mazzone, Mark J Smyth, Thomas Tüting, Michael Hölzel
Inhibitors of the receptor tyrosine kinase c-MET are currently used in the clinic to target oncogenic signaling in tumor cells. We found that concomitant c-MET inhibition promoted adoptive T cell transfer and checkpoint immunotherapies in murine cancer models by increasing effector T cell infiltration in tumors. This therapeutic effect was independent of tumor cell-intrinsic c-MET dependence. Mechanistically, c-MET inhibition impaired the reactive mobilization and recruitment of neutrophils into tumors and draining lymph nodes in response to cytotoxic immunotherapies...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045894/from-oncogene-interference-to-neutrophil-immune-modulation
#8
Vincenzo Bronte
Oncogenes can aid tumor progression in a cancer cell-extrinsic way. In this issue of Immunity, Glodde et al. (2017) demonstrate that interference with c-MET tyrosine kinase receptor can relieve neutrophil-dependent immune suppression and unleash the effectiveness of immunotherapy even in the context of c-MET-independent tumors.
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045540/phase-ii-trial-of-pembrolizumab-in-patients-with-platinum-refractory-germ-cell-tumors-a-hoosier-cancer-research-network-study-gu14-206
#9
N Adra, L H Einhorn, S K Althouse, N R Ammakkanavar, D Musapatika, C Albany, D Vaughn, N H Hanna
Background: Despite remarkable results with salvage standard-dose or high-dose chemotherapy about 15% of patients with relapsed germ-cell tumors (GCT) are incurable. Immune checkpoint inhibitors have produced significant remission in multiple tumor types. We report the first study of immunotherapy in patients with GCT. Patients and Methods: Single arm phase 2 trial investigating pembrolizumab 200mg IV Q3weeks until disease progression in patients with relapsed GCT and no curable options...
October 17, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045528/tumor-regression-and-preservation-of-graft-function-after-combination-with-anti-pd-1-immunotherapy-without-immunosuppressant-titration
#10
C-K Wu, G-D Juang, H-C Lai
No abstract text is available yet for this article.
August 2, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045514/exploratory-analysis-of-the-association-of-depth-of-response-and-survival-in-patients-with-metastatic-non-small-cell-lung-cancer-treated-with-a-targeted-therapy-or-immunotherapy
#11
C E McCoach, G M Blumenthal, L Zhang, A Myers, S Tang, R Sridhara, P Keegan, R Pazdur, R C Doebele, D Kazandjian
Background: Response Evaluation Criteria in Solid Tumors (RECIST) permits rapid evaluation of new therapeutic strategies in cancer. However, RECIST does not capture the heterogeneity of response in highly active therapies. Depth of tumor response may provide a more granular view of response. We explored the association between, depth of response (DepOR), with overall survival (OS) and progression free survival (PFS) for patients with NSCLC being treated with an ALK inhibitor (ALKi) or an anti-PD-1 antibody (Ab)...
August 2, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045511/mechanisms-regulating-t-cell-infiltration-and-activity-in-solid-tumors
#12
E Lanitis, D Dangaj, M Irving, G Coukos
T-lymphocytes play a critical role in cancer immunity as evidenced by their presence in resected tumor samples derived from long-surviving patients, and impressive clinical responses to various immunotherapies that reinvigorate them. Indeed, tumors can upregulate a wide array of defense mechanisms, both direct and indirect, to suppress the ability of Tcells to reach the tumor bed and mount curative responses upon infiltration. In addition, patient and tumor genetics, previous antigenic experience, and the microbiome, are all important factors in shaping the T-cell repertoire and sensitivity to immunotherapy...
September 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29044503/clinical-significance-of-programmed-cell-death-ligand-1-expression-and-the-immune-microenvironment-at-the-invasive-front-of-colorectal-cancers-with-high-microsatellite-instability
#13
Shotaro Korehisa, Eiji Oki, Makoto Iimori, Yu Nakaji, Mototsugu Shimokawa, Hiroshi Saeki, Shinji Okano, Yoshinao Oda, Yoshihiko Maehara
Immunotherapy is reportedly effective in colorectal cancers (CRCs) with high microsatellite instability (MSI-H); however, the specific cell types that respond to immune checkpoint therapy are unclear. Herein, we aimed to examine the expression of programmed cell death-ligand 1 (PD-L1) and related proteins in MSI-H and microsatellite-stable (MSS) CRCs to investigate the immune microenvironment at the tumor's invasive front. The MSI status was retrospectively assessed in 499 patients undergoing surgical resection of primary CRC; of these, 48 were classified as MSI-H...
October 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29043413/cholecystokinin-receptor-antagonist-alters-pancreatic-cancer-microenvironment-and-increases-efficacy-of-immune-checkpoint-antibody-therapy-in-mice
#14
Jill P Smith, Shangzi Wang, Sandeep Nadella, Sandra A Jablonski, Louis M Weiner
Advanced pancreatic ductal adenocarcinoma (PDAC) has typically been resistant to chemotherapy and immunotherapy; therefore, novel strategies are needed to enhance therapeutic response. Cholecystokinin (CCK) has been shown to stimulate growth of pancreatic cancer. CCK receptors (CCKRs) are present on pancreatic cancer cells, fibroblasts, and lymphocytes. We hypothesized that CCKR blockade would improve response to immune checkpoint antibodies by promoting influx of tumor-infiltrating lymphocytes (TILs) and reducing fibrosis...
October 17, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29043377/-lung-cancer-what-has-been-confirmed-in-therapy
#15
REVIEW
D F Heigener, M Reck
Metastatic non-small cell lung cancer has now been subdivided into several subtypes. The five basic principles of treatment include chemotherapy, anti-angiogenic therapy, targeted therapy, immunotherapy and early palliative care. The latter should be implemented for all patients with metastatic lung cancer. The use of the other modalities depends on the histological subtype, as well as on the immunohistochemical and molecular features of the tumor.
October 17, 2017: Der Internist
https://www.readbyqxmd.com/read/29042640/validation-of-multiplex-immunofluorescence-panels-using-multispectral-microscopy-for-immune-profiling-of-formalin-fixed-and-paraffin-embedded-human-tumor-tissues
#16
Edwin R Parra, Naohiro Uraoka, Mei Jiang, Pamela Cook, Don Gibbons, Marie-Andrée Forget, Chantale Bernatchez, Cara Haymaker, Ignacio I Wistuba, Jaime Rodriguez-Canales
Immune-profiling is becoming an important tool to identify predictive markers for the response to immunotherapy. Our goal was to validate multiplex immunofluorescence (mIF) panels to apply to formalin-fixed and paraffin-embedded tissues using a set of immune marker antibodies, with the Opal™ 7 color Kit (PerkinElmer) in the same tissue section. We validated and we described two panels aiming to characterize the expression of PD-L1, PD-1, and subsets of tumor associated immune cells. Panel 1 included pancytokeratin (AE1/AE3), PD-L1, CD4, CD8, CD3, CD68, and DAPI, and Panel 2 included pancytokeratin, PD-1, CD45RO, granzyme B, CD57, FOXP3, and DAPI...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29042417/restoration-of-natural-killer-cell-anti-metastatic-activity-by-il-12-and-checkpoint-blockade
#17
Isabel Ohs, Laura Ducimetiere, Joana Marinho, Paulina Kulig, Burkhard Becher, Sonia Tugues
Immune checkpoint therapies target tumor antigen-specific T cells, but less is known about their effects on natural killer (NK) cells, which help control metastasis. In studying the development of lung metastases, we found that NK cells lose their cytotoxic capacity and acquire a molecular signature defined by the expression of co-inhibitory receptors. In an effort to overcome this suppressive mechanism, we evaluated NK cell responses to the immunostimulatory cytokine IL-12. Exposure to IL-12 rescued the cytotoxicity of NK cells but also led to the emergence of an immature NK cell population which expressed high levels of the co-inhibitory molecules PD-1, Lag-3 and TIGIT, thereby limiting NK cell-mediated control of pulmonary metastases...
October 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/29042364/a-cd200r-cd28-fusion-protein-appropriates-an-inhibitory-signal-to-enhance-t-cell-function-and-therapy-of-murine-leukemia
#18
Shannon K Oda, Andrew W Daman, Nicolas M Garcia, Felecia Wagener, Thomas M Schmitt, Xiaoxia Tan, Aude G Chapuis, Philip D Greenberg
Acute myeloid leukemia (AML), the most common adult acute leukemia in the U.S., has the poorest survival rate, with 26% of patients surviving 5 years. Adoptive immunotherapy with T cells genetically modified to recognize tumors is a promising and evolving treatment option. However, antitumor activity, particularly in the context of progressive leukemia, can be dampened both by limited costimulation and triggering of immunoregulatory checkpoints that attenuate T cell responses. Expression of CD200 (OX2), a negative regulator of T cell function that binds CD200R, is commonly increased in leukemia and other malignancies, and is associated with poor prognosis in leukemia patients...
October 17, 2017: Blood
https://www.readbyqxmd.com/read/29041905/clinicopathological-and-prognostic-significance-of-programmed-death-ligand-1-expression-in-breast-cancer-a-meta-analysis
#19
Hye Min Kim, Jinae Lee, Ja Seung Koo
BACKGROUND: Programmed cell death-ligand 1 (PD-L1) may be a useful molecule for targeted immunotherapy. Therefore, this meta-analysis aimed to investigate PD-L1 expression in breast cancer and its associations with clinicopathological factors and outcomes, which may help determine whether PD-L1 expression is a useful prognostic marker. METHODS: The Medline Ovid, Cochrane, PubMed, Google Scholar, and Web of Knowledge databases were searched for studies that evaluated the prognostic or clinicopathological significance of PD-L1 expression in patients with breast cancer, and reported at least one survival-related outcome...
October 17, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29040190/novel-therapeutics-for-ovarian-cancer-the-11th-biennial-rivkin-center-ovarian-cancer-research-symposium
#20
Neil Johnson, John B Liao
OBJECTIVE: The aim of this study was to summarize developments in novel therapeutics for ovarian cancer presented at the Ovarian Cancer Research Symposium held at the University of Washington. METHODS: A symposium of the leaders in ovarian cancer research was convened to present and discuss current advances and future directions in ovarian cancer research. RESULTS: The fourth session was held on September 13, 2016, and focused on Novel Therapeutics for Ovarian Cancer...
October 17, 2017: International Journal of Gynecological Cancer
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