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Cancer immunology

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https://www.readbyqxmd.com/read/28915659/data-driven-analysis-of-immune-infiltrate-in-a-large-cohort-of-breast-cancer-and-its-association-with-disease-progression-er-activity-and-genomic-complexity
#1
Ruth Dannenfelser, Marianne Nome, Andliena Tahiri, Josie Ursini-Siegel, Hans Kristian Moen Vollan, Vilde D Haakensen, Åslaug Helland, Bjørn Naume, Carlos Caldas, Anne-Lise Børresen-Dale, Vessela N Kristensen, Olga G Troyanskaya
The tumor microenvironment is now widely recognized for its role in tumor progression, treatment response, and clinical outcome. The intratumoral immunological landscape, in particular, has been shown to exert both pro-tumorigenic and anti-tumorigenic effects. Identifying immunologically active or silent tumors may be an important indication for administration of therapy, and detecting early infiltration patterns may uncover factors that contribute to early risk. Thus far, direct detailed studies of the cell composition of tumor infiltration have been limited; with some studies giving approximate quantifications using immunohistochemistry and other small studies obtaining detailed measurements by isolating cells from excised tumors and sorting them using flow cytometry...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915554/resistance-to-ctla-4-checkpoint-inhibition-reversed-through-selective-elimination-of-granulocytic-myeloid-cells
#2
Paul E Clavijo, Ellen C Moore, Jianhong Chen, Ruth J Davis, Jay Friedman, Young Kim, Carter Van Waes, Zhong Chen, Clint T Allen
PURPOSE: Local immunosuppression remains a critical problem that limits clinically meaningful response to checkpoint inhibition in patients with head and neck cancer. Here, we assessed the impact of MDSC elimination on responses to CTLA-4 checkpoint inhibition. EXPERIMENTAL DESIGN: Murine syngeneic carcinoma immune infiltrates were characterized by flow cytometry. Granulocytic MDSCs (gMDSCs) were depleted and T-lymphocyte antigen-specific responses were measured...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28913891/venous-thromboembolism-and-risk-of-cancer-in-patients-with-rheumatoid-arthritis
#3
A B Pedersen, J Vandenbroucke, E Horváth-Puhó, H T Sørensen
BACKGROUND: It is unknown whether venous thromboembolism (VTE) in rheumatoid arthritis (RA) patients can be marker of occult cancer. OBJECTIVES: To examine cancer risk subsequent to VTE among RA patients compared with cancer risk in RA cohort without VTE and in a general population without RA and without VTE. PATIENTS/METHODS: All RA patients with a first-time diagnosis of VTE (index date) during 1978-2013 and comparison cohorts were identified from population-based registries in Denmark...
September 15, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28912405/-exploring-the-possibility-of-new-biomarkers-of-immune-checkpoint-inhibitors-for-non-small-cell-lung-cancer-nsclc
#4
Yuki Owada, Takuya Inoue, Yuzuru Watanabe, Mitsuro Fukuhara, Takumi Yamaura, Satoshi Muto, Yuki Matsumura, Takeo Hasegawa, Daisuke Tanaka, Ryo Kanno, Emi Ito, Hideaki Nanamiya, Junichi Imai, Takao Isogai, Shinya Watanabe, Hiroyuki Suzuki
Mutation burden in a tumor, presumably involving neo-antigens in the tumor tissue, is also thought to be one of the better predictors for the efficacy of immune checkpoint inhibitors. However, it is difficult to analyze the mutation burden routinely in the clinic. Here, we describe more convenient factors that can be used as surrogate markers of mutation burden. Ninety-four patients with NSCLC who underwent resection in our institution were recruited for this study. Mutation burden and major gene alterations were analyzed by using next generation sequencing...
September 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28912377/immune-response-in-the-thyroid-cancer-microenvironment-making-immunotherapy-a-possible-mission
#5
Robert C Mould, Jacob P van Vloten, Amanda W K AuYeung, Khalil Karimi, Byram W Bridle
The incidence of thyroid cancers has been steadily increasing worldwide over the past few decades. Although five-year survival rates for differentiated thyroid cancers are upwards of 90%, clinical outcomes for patients with undifferentiated, recurrent and/or metastatic disease are often dismal despite conventional interventions. As such, there is a demand for novel treatment options. Cancer immunotherapy represents the ultimate form of personalized medicine by leveraging the specificity and potency of a patient's immune system to kill their tumour...
September 14, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28912369/customized-viral-immunotherapy-for-hpv-associated-cancer
#6
Matthew J Atherton, Kyle B Stephenson, Jonathan Pol, Fuan Wang, Charles Lefebvre, David F Stojdl, Jake K Nikota, Anna Dvorkin-Gheva, Andrew Nguyen, Lan Chen, Stephanie Johnson-Obaseki, Patrick J Villeneuve, Jean-Simon Diallo, Jim Dimitroulakos, Yonghong Wan, Brian D Lichty
The viral transforming proteins E6 and E7 make human papilloma virus positive (HPV+) malignancies an attractive target for cancer immunotherapy. However, therapeutic vaccination exerts limited efficacy in the setting of advanced disease. We designed a strategy to induce substantial specific immune responses against multiple epitopes of E6 and E7 proteins based on an attenuated transgene from HPV serotypes 16 and 18 that is incorporated into MG1-Maraba virotherapy (MG1-E6E7). Mutations introduced to the transgene abrogate the ability of E6 and E7 to perturb p53 and retinoblastoma, respectively, while maintaining the ability to invoke tumor-specific, multi-functional CD8+ T-cell responses...
September 14, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28912090/immuno-oncology-and-its-opportunities-for-interventional-radiologists-immune-checkpoint-inhibition-and-potential-synergies-with-interventional-oncology%C3%A2-procedures
#7
REVIEW
Ryan M Hickey, Laura M Kulik, Halla Nimeiri, Aparna Kalyan, Sheetal Kircher, Kush Desai, Ahsun Riaz, Robert J Lewandowski, Riad Salem
Immunotherapy, specifically the use of immune checkpoint inhibitors, offers a new approach to fighting cancer. Although the results of treatment with immune checkpoint inhibition alone have been remarkable for certain cancers, these results are not universal. Preclinical and early clinical studies indicate the potential for synergistic effects when immune checkpoint inhibition is combined with immunogenic local therapies such as ablation and embolization. This review offers an overview of immunology as it relates to immune checkpoint inhibition and the possibilities for synergy when combined with interventional radiology treatments...
September 12, 2017: Journal of Vascular and Interventional Radiology: JVIR
https://www.readbyqxmd.com/read/28910694/an-epidemiologic-perspective-on-the-stem-cell-hypothesis-in-human-carcinogenesis
#8
REVIEW
David Schottenfeld
BACKGROUND: Tomasetti and Vogelstein have hypothesized that the patterns of cancer incidence in various cells and tissues are highly correlated with the estimated lifetime number of stem cell divisions. The authors reviewed the risks in tissues of 17 types of cancer from the United States and 69 additional countries. Positive correlations were observed consistently between the tissue - specific cancer incidence and the estimated lifetime number of stem cell divisions. The authors concluded that approximately two-thirds of global cancer incidence may be attributed to random DNA replication errors...
September 11, 2017: Cancer Epidemiology
https://www.readbyqxmd.com/read/28903456/tumor-reductive-therapies-and-antitumor-immunity
#9
REVIEW
Huiqin Guo, Kangla Tsung
Tumor reductive therapy is to reduce tumor burden through direct killing of tumor cells. So far, there is no report on the connection between antitumor immunity and tumor reductive therapies. In the last few years, a new category of cancer treatment, immunotherapy, emerged and they are categorized separately from classic cytotoxic treatments (chemo and radiation therapy). The most prominent examples include cellular therapies (LAK and CAR-T) and immune checkpoint inhibitors (anti-PD-1 and CTLA-4). Recent advances in clinical immunotherapy and our understanding of the mechanism behind them revealed that these therapies have a closer relationship with classic cancer treatments than we thought...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28902490/direct-intra-nuclear-anticancer-drug-delivery-via-polydimethylsiloxane-nanoparticles-in-vitro-and-in-vivo-xenograft-studies
#10
Gargi Mishra, Souryadeep Bhattacharyya, Vipul Bhatia, Bushra Ateeq, Ashutosh Sharma, Sri Sivakumar
Direct delivery of anticancer drugs to nuclei of tumor cells is required to enhance the therapeutic activity which can be achieved by a nuclear localization signal (NLS) or peptide-decorated nano-vehicles. However, NLS/peptide-based approaches may create certain undesirable immunological responses and the utilized synthesis processes are generally labor intensive. To this end, we report ligand-free, enhanced intra-nuclear delivery of Doxorubicin (Dox) to different cancer cells via porous polydimethylsiloxane (PDMS) nanoparticles (NPs)...
September 13, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28901740/inhibiting-metastasis-and-preventing-tumor-relapse-by-triggering-host-immunity-with-tumor-targeted-photodynamic-therapy-using-photosensitizer-loaded-functional-nanographenes
#11
Xinhe Yu, Duo Gao, Liquan Gao, Jianhao Lai, Chenran Zhang, Yang Zhao, Lijun Zhong, Bing Jia, Fan Wang, Xiaoyuan Chen, Zhaofei Liu
Effective cancer therapy depends not only on destroying the primary tumor, but also on conditioning the host immune system to recognize and eliminate residual tumor cells and prevent metastasis. In this study, a tumor integrin αvβ6-targeting peptide (the HK peptide)-functionalized graphene oxide (GO) was coated with a photosensitizer (HPPH). The resulting GO conjugate, GO(HPPH)-PEG-HK, was investigated whether it could destroy primary tumors and boost host antitumor immunity. We found that GO(HPPH)-PEG-HK exhibited significantly higher tumor uptake than GO(HPPH)-PEG and HPPH...
September 13, 2017: ACS Nano
https://www.readbyqxmd.com/read/28900679/ctla-4-an-essential-immune-checkpoint-for-t-cell-activation
#12
Shunsuke Chikuma
The response of peripheral T lymphocytes (T cell) is controlled by multiple checkpoints to avoid unwanted activation against self-tissues. Two opposing costimulatory receptors, CD28 and CTLA-4, on T cells bind to the same ligands (CD80 and CD86) on antigen-presenting cells (APCs), and provide positive and negative feedback for T-cell activation, respectively. Early studies suggested that CTLA-4 is induced on activated T cells and binds to CD80/CD86 with much stronger affinity than CD28, providing a competitive inhibition...
September 13, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28900678/socs1-regulator-of-t-cells-in-autoimmunity-and-cancer
#13
Subburaj Ilangumaran, Diwakar Bobbala, Sheela Ramanathan
SOCS1 is a negative feedback regulator of cytokine and growth factor receptor signaling, and plays an indispensable role in attenuating interferon gamma signaling. Studies on SOCS1-deficient mice have established a crucial role for SOCS1 in regulating CD8(+) T cell homeostasis. In the thymus, SOCS1 prevents thymocytes that had failed positive selection from surviving and expanding, ensures negative selection and prevents inappropriate developmental skewing toward the CD8 lineage. In the periphery, SOCS1 not only controls production of T cell stimulatory cytokines but also attenuates the sensitivity of CD8(+) T cells to synergistic cytokine stimulation and antigen non-specific activation...
September 13, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28900328/immune-checkpoint-blockers-and-ovarian-cancer
#14
REVIEW
Chinmoy K Bose
Although the idea, called "cancer immunotherapy," is very appealing and has previously been shown to work in several mouse models of cancer, it has in general been very difficult to translate cancer immunotherapy approaches to humans. Because of this frustration, by the 1990s, many scientists and biotechnology companies had given up on the idea of cancer immunotherapy. After few years, first detection T-cell suppression of effect of cytotoxic T-lymphocyte antigen-4 (CTLA4) molecule was established. Antibody (Ab) to CTLA4 could increase T-cell starting a completely new age of tumor immunology...
April 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/28900154/synthesis-and-evaluation-of-gm2-monophosphoryl-lipid-a-conjugate-as-a-fully-synthetic-self-adjuvant-cancer-vaccine
#15
Zhifang Zhou, Satadru S Mandal, Guochao Liao, Jiatong Guo, Zhongwu Guo
An efficient method was developed for the synthesis of a GM2 derivative suitable for the conjugation with various biomolecules. This GM2 derivative was covalently linked to keyhole limpet hemocyanin (KLH) and monophosphoryl lipid A (MPLA) to form novel therapeutic cancer vaccines. Immunological evaluations of the resultant conjugates in mice revealed that they elicited robust GM2-specific overall and IgG antibody responses. Moreover, the GM2-MPLA conjugate was disclosed to elicit strong immune responses without the use of an adjuvant, proving its self-adjuvant property...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28898532/immunological-efficacy-of-herbal-medicines-in-prostate-cancer-patients-treated-by-personalized-peptide-vaccine
#16
Noriko Koga, Fukuko Moriya, Kayoko Waki, Akira Yamada, Kyogo Itoh, Masanori Noguchi
This randomized phase II study investigated the immunological efficacy of herbal medicines (HMs) using Hochu-ekki-to and Keishi-bukuryo-gan in combination with personalized peptide vaccination (PPV) for castration-resistant prostate cancer (CRPC). Seventy patients with CRPC were assigned to two arms; PPV plus HMs or PPV alone. Two to four peptides were chosen from 31 peptides derived from cancer antigens for the eight-time subcutaneous injection of PPV according to the patient's human leukocyte antigen type and levels of antigen-specific immunoglobulin G (IgG) titer before PPV treatment...
September 12, 2017: Cancer Science
https://www.readbyqxmd.com/read/28895911/therapeutic-implications-of-autophagy-inducers-in-immunological-disorders-infection-and-cancer
#17
REVIEW
Sanguine Byun, Eunjung Lee, Ki Won Lee
Autophagy is an essential catabolic program that forms part of the stress response and enables cells to break down their own intracellular components within lysosomes for recycling. Accumulating evidence suggests that autophagy plays vital roles in determining pathological outcomes of immune responses and tumorigenesis. Autophagy regulates innate and adaptive immunity affecting the pathologies of infectious, inflammatory, and autoimmune diseases. In cancer, autophagy appears to play distinct roles depending on the context of the malignancy by either promoting or suppressing key determinants of cancer cell survival...
September 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28892265/effects-of-preemptive-analgesia-with-flurbiprofen-ester-on-lymphocytes-and-natural-killer-cells-in-patients-undergoing-esophagectomy-a-randomized-controlled-pilot-study
#18
Yi Zhou, Jinxi Huang, Yu Bai, Changsheng Li, Xihua Lu
BACKGROUND: Tumors may induce systemic immune dysfunction, which can be aggravated by surgery and anesthesia/analgesia. Data on the effect of flurbiprofen preemptive analgesia on immune dysfunction is limited. The aim of this study was to investigate the effect of flurbiprofen preemptive analgesia on lymphocytes and natural killer (NK) cells in patients undergoing thoracotomy and thoracoscopy radical esophagectomy, and to explore the analgesic methods suitable for tumor patients. METHODS: This was a randomized controlled pilot study of 89 patients with esophageal cancer treated with surgery at the Henan Cancer Hospital between January 1, 2015 and December 31, 2016...
September 11, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/28891906/first-in-human-treatment-with-a-dendritic-cell-targeting-lentiviral-vector-expressing-ny-eso-1-lv305-induces-deep-durable-response-in-refractory-metastatic-synovial-sarcoma-patient
#19
Seth M Pollack, Hailing Lu, Sacha Gnjatic, Neeta Somaiah, Ryan B O'Malley, Robin L Jones, Frank J Hsu, Jan Ter Meulen
Effective induction of antitumor T cells is a pivotal goal of cancer immunotherapy. To this end, lentiviral vectors (LV) are uniquely poised to directly prime CD8 T-cell responses via transduction of dendritic cells in vivo and have shown promise as active cancer therapeutics in preclinical tumor models. However, until now, significant barriers related to production and regulation have prevented their widespread use in the clinic. We developed LV305, a dendritic cell-targeting, integration-deficient, replication incompetent LV from the ZVex platform, encoding the full-length cancer-testis antigen NY-ESO-1...
October 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28891128/helicobacter-inflammation-immunology-and-vaccines
#20
REVIEW
Karen Robinson, Kazuyo Kaneko, Leif Percival Andersen
Helicobacter pylori is usually acquired in early childhood and the infection persists lifelong without causing symptoms. In a small of cases, the infection leads to gastric or duodenal ulcer disease, or gastric cancer. Why disease occurs in these individuals remains unclear, however the host response is known to play a very important part. Understanding the mechanisms involved in maintaining control over the immune and inflammatory response is therefore extremely important. Vaccines against H. pylori have remained elusive but are desperately needed for the prevention of gastric carcinogenesis...
September 2017: Helicobacter
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