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Cancer immunotherapy

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https://www.readbyqxmd.com/read/29150846/cancer-stem-cells-as-targets-for-immunotherapy
#1
REVIEW
Amy S Codd, Takayuki Kanaseki, Toshihiko Torigo, Zsuzsanna Tabi
Current cancer therapies target the bulk of the tumour, while a population of highly resistant tumour cells may be able to repopulate the tumour and metastasise to new sites. Cancer cells with such stem cell-like characteristics can be identified based on their phenotypic and/or functional features which may open up ways for their targeted elimination. In this review we discuss potential off-target effects of inhibiting cancer stem-cell self-renewal pathways on immune cells, and summarise some recent immunological studies specifically targeting cancer stem cells based on their unique antigen expression...
November 18, 2017: Immunology
https://www.readbyqxmd.com/read/29150702/high-pdl1-mrna-expression-predicts-better-survival-of-stage-pt1-non-muscle-invasive-bladder-cancer-nmibc-patients
#2
Johannes Breyer, Ralph M Wirtz, Wolfgang Otto, Philipp Erben, Thomas S Worst, Robert Stoehr, Markus Eckstein, Stefan Denzinger, Maximilian Burger, Arndt Hartmann
INTRODUCTION AND OBJECTIVES: Checkpoint inhibition has emerged as new therapeutic option in muscle-invasive bladder cancer. The objective of the present study was to evaluate the prognostic role of PD1 and PDL1 expression in non-muscle-invasive bladder cancer (NMIBC) and establish an objective measuring method using RNA quantification. MATERIALS AND METHODS: We retrospectively analyzed clinical data and formalin-fixed paraffin-embedded tissues (FFPE) of patients with stage pT1 NMIBC who underwent transurethral resection of the bladder...
November 17, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29150280/nk-cell-recruitment-and-exercise-potential-immunotherapeutic-role-of-shear-stress-and-endothelial-health
#3
William Evans
Positive cancer patient outcomes, including increased time to recurrent events, have been associated with increased counts and function of natural killer (NK) cells. NK cell counts and function are elevated following acute exercise, and the generally accepted mechanism of increased recruitment suggests that binding of epinephrine releases NK cells from endothelial tissue via decreases in adhesion molecules following. I propose that blood flow-induced shear stress may also play a role in NK cell recruitment from the endothelium...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29148862/in-this-issue-cancer-immunity-and-immunotherapy
#4
Himanshu Kumar, Adrian Bot
No abstract text is available yet for this article.
November 2, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/29147629/trial-watch-immune-checkpoint-blockers-for-cancer-therapy
#5
REVIEW
Claire Vanpouille-Box, Claire Lhuillier, Lucillia Bezu, Fernando Aranda, Takahiro Yamazaki, Oliver Kepp, Jitka Fucikova, Radek Spisek, Sandra Demaria, Silvia C Formenti, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi
Immune checkpoint blockers (ICBs) are literally revolutionizing the clinical management of an ever more diversified panel of oncological indications. Although considerable attention persists around the inhibition of cytotoxic T lymphocyte-associated protein 4 (CTLA4) and programmed cell death 1 (PDCD1, best known as PD-1) signaling, several other co-inhibitory T-cell receptors are being evaluated as potential targets for the development of novel ICBs. Moreover, substantial efforts are being devoted to the identification of biomarkers that reliably predict the likelihood of each patient to obtain clinical benefits from ICBs in the absence of severe toxicity...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147627/stat1-gene-deficient-mice-develop-accelerated-breast-cancer-growth-and-metastasis-which-is-reduced-by-il-17-blockade
#6
Sanjay Varikuti, Steve Oghumu, Mohamad Elbaz, Greta Volpedo, Dinesh K Ahirwar, Pablo C Alarcon, Rachel H Sperling, Ellen Moretti, Marissa S Pioso, Jennifer Kimble, Mohd W Nasser, Ramesh K Ganju, Cesar Terrazas, Abhay R Satoskar
Signal transducer and activator of transcription 1 (STAT1) mediates interferon gamma signaling which activates the expression of various genes related to apoptosis, inflammation, cell cycle and angiogenesis. Several experimental and clinical studies have investigated the role of STAT1 in primary tumor growth in breast cancer; however, its role in tumor metastasis remains to be determined. To determine the role of STAT1 in breast cancer metastasis, we analyzed growth and metastasis in WT or STAT1(-/-) mice orthotopically implanted with metastatic 4T1...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147626/functional-t-cells-targeting-tumor-associated-antigens-are-predictive-for-recurrence-free-survival-of-patients-with-radically-operated-non-small-cell-lung-cancer
#7
Seyer Safi, Yoshikane Yamauchi, Anchana Rathinasamy, Slava Stamova, Martin Eichhorn, Arne Warth, Geraldine Rauch, Hendrik Dienemann, Hans Hoffmann, Philipp Beckhove
In this prospective study, we examined postoperative follow-up and preoperative IFN-γ T cell responses against 14 non-small cell lung cancer (NSCLC)-associated antigens in the blood of 51 patients with NSCLC, 7 patients with benign pulmonary tumors, and 10 tumor-free patients by enzyme-linked immunospot assay. The phenotype and function of T cells specific for tumor-associated antigens (TAAs) in the blood or tumor tissue of 9 NSCLC patients were characterized in detail using TNF-α, IL-2, and IFN-γ cytokine capture assays...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147616/mrna-expression-levels-of-genes-involved-in-antitumor-immunity-identification-of-a-3-gene-signature-associated-with-prognosis-of-muscle-invasive-bladder-cancer
#8
Constance Le Goux, Sophie Vacher, Géraldine Pignot, Mathilde Sibony, Nicolas Barry Delongchamps, Benoit Terris, Eliane Piaggio, Marc Zerbib, Diane Damotte, Ivan Bieche
Immunotherapy for bladder cancer has given promising results. Here we aimed to evaluate the possible involvement and prognostic value of 33 genes involved in the immune response during bladder carcinogenesis. Expression levels were assessed by quantitative real-time RT-PCR in normal and tumor human bladder samples. Immunohistochemistry was performed to evaluate the protein expression of 2 genes and relation of the mRNA and protein levels was analyzed. Tumors were obtained from 154 patients (83 with muscle-invasive bladder cancer [MIBC] and 71 non-MIBC [NMIBC]) who underwent transurethral bladder resection or radical cystectomy between 2002 and 2006...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147610/host-immune-response-index-in-gastric-cancer-identified-by-comprehensive-analyses-of-tumor-immunity
#9
Charny Park, Junhun Cho, Jeeyun Lee, So Young Kang, Ji Yeong An, Min Gew Choi, Jun Ho Lee, Tae Sung Sohn, Jae Moon Bae, Sung Kim, Seung Tae Kim, Se Hoon Park, Joon Oh Park, Won Ki Kang, Insuk Sohn, Sin Ho Jung, Myung-Soo Kang, Kyoung-Mee Kim
Tumor infiltrating lymphocytes (TIL) in Epstein-Barr virus (EBV)-associated/microsatellite-unstable (MSI) gastric carcinomas (GC) constitute immune-active principal cellular components of tumor microenvironment and contribute to better prognosis. With the remarkable success of cancer immunotherapies, there is an urgent need for a comprehensive understanding of tumor-immune interactions in patients with GC in the context of host immune response. To identify GC subtype-specific immune response gene set, we tested differentially expressed genes for MSI and EBV+ GC subtypes in randomly selected test set (n = 278) in merged ACRG-SMC microarray and TCGA RNA sequencing data set...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147605/egfr-mutation-correlates-with-uninflamed-phenotype-and-weak-immunogenicity-causing-impaired-response-to-pd-1-blockade-in-non-small-cell-lung-cancer
#10
Zhong-Yi Dong, Jia-Tao Zhang, Si-Yang Liu, Jian Su, Chao Zhang, Zhi Xie, Qing Zhou, Hai-Yan Tu, Chong-Rui Xu, Li-Xu Yan, Yu-Fa Li, Wen-Zhao Zhong, Yi-Long Wu
Patients with EGFR mutations showed unfavorable response to programmed cell death-1 (PD-1) blockade immunotherapy in non-small cell lung cancer (NSCLC). Yet the underlying association between EGFR mutation and immune resistance remains largely unclear. We performed an integrated analysis of PD-ligand 1(PD-L1)/CD8 expression and mutation profile based on the repository database and resected early-stage NSCLC in Guangdong Lung Cancer Institute (GLCI). Meanwhile, 2 pool-analyses were set to clarify the correlation between EGFR mutation and PD-L1 expression, and the association of EGFR status with response to anti-PD-1/L1 therapy...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147453/ctla-4-genetic-variants-rs11571317-and-rs3087243-role-in-susceptibility-and-progression-of-breast-cancer
#11
Maruthi Goske, V R Vinish Ramachander, Prasanna Latha Komaravalli, P Fazul Rahman, Chandrasekhar Rao, Parveen Jahan
Background: Dysfunctional regulation at immune checkpoints may lead to escape of the tumor cells and gives a scope to set in the unresolved Breast cancer (BC). The major anti-tumor retort is cell-mediated response which involves T lymphocytes. CTLA-4 (Cytotoxic T lymphocyte associated protein-4) with immune suppressive function and tolerance is associated with various autoimmune diseases and cancers including BC. The present study deals with CTLA-4 gene selected polymorphisms (rs11571317 C/T and rs3087243G/A) to explore their relation with breast cancer susceptibility and progression in BC patients...
October 2017: World Journal of Oncology
https://www.readbyqxmd.com/read/29147025/sphingolipid-metabolism-in-cancer-signalling-and-therapy
#12
REVIEW
Besim Ogretmen
Sphingolipids, including the two central bioactive lipids ceramide and sphingosine-1-phosphate (S1P), have opposing roles in regulating cancer cell death and survival, respectively, and there have been exciting developments in understanding how sphingolipid metabolism and signalling regulate these processes in response to anticancer therapy. Recent studies have provided mechanistic details of the roles of sphingolipids and their downstream targets in the regulation of tumour growth and response to chemotherapy, radiotherapy and/or immunotherapy using innovative molecular, genetic and pharmacological tools to target sphingolipid signalling nodes in cancer cells...
November 17, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29147022/conventional-cd4-t-cells-present-bacterial-antigens-to-induce-cytotoxic-and-memory-cd8-t-cell-responses
#13
Aránzazu Cruz-Adalia, Guillermo Ramirez-Santiago, Jesús Osuna-Pérez, Mónica Torres-Torresano, Virgina Zorita, Ana Martínez-Riaño, Viola Boccasavia, Aldo Borroto, Gloria Martínez Del Hoyo, José María Gozález-Granado, Balbino Alarcón, Francisco Sánchez-Madrid, Esteban Veiga
Bacterial phagocytosis and antigen cross-presentation to activate CD8(+) T cells are principal functions of professional antigen presenting cells. However, conventional CD4(+) T cells also capture and kill bacteria from infected dendritic cells in a process termed transphagocytosis (also known as transinfection). Here, we show that transphagocytic T cells present bacterial antigens to naive CD8(+) T cells, which proliferate and become cytotoxic in response. CD4(+) T-cell-mediated antigen presentation also occurs in vivo in the course of infection, and induces the generation of central memory CD8(+) T cells with low PD-1 expression...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29146881/beta-adrenergic-signaling-impairs-anti-tumor-cd8-t-cell-responses-to-b-cell-lymphoma-immunotherapy
#14
Michael D Nissen, Erica K Sloan, Stephen R Mattarollo
Beta-adrenergic receptor (betaAR) signaling regulates many physiological processes, including immune system responses. There is growing evidence also for betaAR-induced modulation of cancer growth and metastasis. In the Eu-myc mouse model of B-cell lymphoma, we investigated the effects of chronically elevated betaAR signaling on lymphoma progression and anti-tumor immunity, as well as the impact on cancer immunotherapy. Chronic treatment with the non-selective beta-agonist isoprenaline promoted lymphoma development in a manner dependent on signaling within the hematopoietic compartment...
November 16, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29146734/humanized-mice-in-studying-efficacy-and-mechanisms-of-pd-1-targeted-cancer-immunotherapy
#15
Minan Wang, Li-Chin Yao, Mingshan Cheng, Danying Cai, Jan Martinek, Chong-Xian Pan, Wei Shi, Ai-Hong Ma, Ralph W De Vere White, Susan Airhart, Edison T Liu, Jacques Banchereau, Michael A Brehm, Dale L Greiner, Leonard D Shultz, Karolina Palucka, James G Keck
Establishment of an in vivo small animal model of human tumor and human immune system interaction would enable preclinical investigations into the mechanisms underlying cancer immunotherapy. To this end, non-obese diabetic (NOD).Cg-Prkdc(scid)IL2rg(tm1Wjl) /Sz (null; NSG) mice were transplanted with human (h)CD34(+) hematopoietic progenitor and stem cells, which leads to the development of human hematopoietic and immune systems [humanized NSG (HuNSG)]. HuNSG mice received human leukocyte antigen partially matched tumor implants from patient-derived xenografts [PDX; nonsmall cell lung cancer (NSCLC), sarcoma, bladder cancer, and triple-negative breast cancer (TNBC)] or from a TNBC cell line-derived xenograft (CDX)...
November 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29146617/cure-in-advanced-renal-cell-cancer-is-it-an-achievable-goal
#16
Dhanusha Sabanathan, John J Park, Manuel Marquez, Louise Francisco, Natalie Byrne, Howard Gurney
BACKGROUND: Immunotherapy has historically been of interest in the management of metastatic renal cell cancer (mRCC) because of its relative chemoresistance and the reproducible but low incidence of spontaneous remission in metastatic disease. Recently, targeted immunotherapies in the form of checkpoint inhibitors have shown durable responses in approximately 20%-30% of patients with solid tumors, with a much more acceptable side-effect profile. Anti-programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 antibodies rely on the presence of host T cells in the tumor microenvironment to be stimulated in order to activate an antitumor response...
November 16, 2017: Oncologist
https://www.readbyqxmd.com/read/29146441/combining-immunotherapies-for-the-treatment-of-prostate-cancer
#17
REVIEW
Jason M Redman, James L Gulley, Ravi A Madan
Sipuleucel-T, a therapeutic dendritic-cell vaccine, was Food and Drug Administration-approved for prostate cancer in 2010. No new immunotherapies for prostate cancer have been approved since. However, novel agents and combination approaches offer great promise for improving outcomes for prostate cancer patients. Here we review the latest developments in immunotherapy for prostate cancer. Sipuleucel-T has demonstrated a survival advantage of 4.1 months in metastatic castration-resistant prostate cancer. PSA-TRICOM (PROSTVAC), a prostate-specific antigen-targeted vaccine platform, showed evidence of clinical and immunologic efficacy in early-phase clinical trials, and results from a phase III trial in advanced disease are pending...
December 2017: Urologic Oncology
https://www.readbyqxmd.com/read/29146246/nanoparticle-formulation-improves-doxorubicin-efficacy-by-enhancing-host-antitumor-immunity
#18
Eric M Mastria, Leon Y Cai, Matthew J Kan, Xinghai Li, Jeffrey L Schaal, Steven Fiering, Michael D Gunn, Mark W Dewhirst, Smita K Nair, Ashutosh Chilkoti
Strategies that enhance the host antitumor immune response promise to revolutionize cancer therapy. Optimally mobilizing the immune system will likely require a multi-pronged approach to overcome the resistance developed by tumors to therapy. Recently, it has become recognized that doxorubicin can contribute to re-establishing host antitumor immunity through the generation of immunogenic cell death. However, the potential for delivery strategies to further enhance the immunological effects of doxorubicin has not been adequately examined...
November 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29145974/immunotherapy-for-triple-negative-breast-cancer-existing-challenges-and-exciting-prospects
#19
Hongyan Jia, Cristina I Truica, Bin Wang, Yanhong Wang, Xingcong Ren, Harold A Harvey, Jianxun Song, Jin-Ming Yang
Patients with breast tumors that do not express the estrogen receptor, the progesterone receptor, nor Her-2/neu are hence termed "triple negatives", and generally have a poor prognosis, with high rates of systemic recurrence and refractoriness to conventional therapy regardless of the choice of adjuvant treatment. Thus, more effective therapeutic options are sorely needed for triple-negative breast cancer (TNBC), which occurs in approximately 20% of diagnosed breast cancers. In recent years, exploiting intrinsic mechanisms of the host immune system to eradicate cancer cells has achieved impressive success, and the advances in immunotherapy have yielded potential new therapeutic strategies for the treatment of this devastating subtype of breast cancer...
May 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/29145972/cancer-immunotherapy-getting-brainy-visualizing-the-distinctive-cns-metastatic-niche-to-illuminate-therapeutic-resistance
#20
Mark Owyong, Niloufar Hosseini-Nassab, Gizem Efe, Alexander Honkala, Renske J E van den Bijgaart, Vicki Plaks, Bryan Ronain Smith
The advent of cancer immunotherapy (CIT) and its success in treating primary and metastatic cancer may offer substantially improved outcomes for patients. Despite recent advancements, many malignancies remain resistant to CIT, among which are brain metastases, a particularly virulent disease with no apparent cure. The immunologically unique niche of the brain has prompted compelling new questions in immuno-oncology such as the effects of tissue-specific differences in immune response, heterogeneity between primary tumors and distant metastases, and the role of spatiotemporal dynamics in shaping an effective anti-tumor immune response...
November 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
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