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https://www.readbyqxmd.com/read/29757416/early-changes-in-cd4-t-cell-activation-following-blood-stage-plasmodium-falciparum-infection
#1
Chelsea L Edwards, Susanna S Ng, Dillon Corvino, Marcela Montes de Oca, Fabian de Labastida Rivera, Katia Nones, Vanessa Lakis, Nicola Waddell, Fiona H Amante, James S McCarthy, Christian R Engwerda
We examined transcriptional changes in CD4+ T cells during blood-stage Plasmodium falciparum infection in individuals without a history of previous parasite exposure. CD4+ T cell CXCL8 gene (encoding IL-8) transcription was identified as an early biomarker of sub-microscopic P. falciparum infection, with predictive power for parasite growth. Following anti-parasitic drug treatment, a CD4+ T cell regulatory phenotype developed. PD1 expression on CD49b+ CD4+ T (putative type I regulatory (Tr1)) cells after drug treatment negatively correlated with earlier parasite growth...
May 11, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29706000/ipilimumab-more-and-more-discussed-urgent-need-for-predictive-markers-of-response
#2
B Dréno
Immune checkpoint blockade with anti-CTLA-4 and anti-PD-11 has improved clinical responses and long-term survival benefit for patients with advanced melanoma. These 2 papers1, 2 focus on 2 check point inhibitors. However, the practical interest is different taking in count the quickness of the evolution in the management of metastatic melanoma. This article is protected by copyright. All rights reserved.
April 28, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29566951/composition-of-the-immune-microenvironment-differs-between-carcinomas-metastatic-to-the-lungs-and-primary-lung-carcinomas
#3
Wijendra Senarathne, Semir Vranic, Joanne Xiu, Inga Rose, Peggy Gates, Zoran Gatalica
Lungs are among the most common sites for development of both primary and metastatic carcinomas. Tumor cells expression (TC) of PD-L1 is an important predictor of the of response to immune check-point inhibition in NSCLC, while the composition of the immune cells (IC) in the tumor microenvironment including PD-L1+ cells is believed to predict responses in tumors of some other primary sites. Total mutational load (TML) and microsatellite instability (MSI) also play a role in response to the immune checkpoint blockade...
April 2018: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/29565139/smart-nano-reactors-for-ph-responsive-tumor-homing-mitochondria-targeting-and-enhanced-photodynamic-immunotherapy-of-cancer
#4
Guangbao Yang, Ligeng Xu, Jun Xu, Rui Zhang, Guosheng Song, Yu Chao, Liangzhu Feng, Fengxuan Han, Ziliang Dong, Bin Li, Zhuang Liu
Photodynamic therapy (PDT) is an oxygen-dependent light-triggered non-invasive therapeutic method showing many promising aspects in cancer treatment. For effective PDT, nanoscale carriers are often needed to realize tumor-targeted delivery of photosensitizers, which ideally should further target specific cell organelles that are most vulnerable to reactive oxygen species (ROS). Secondly, as oxygen is critical for PDT-induced cancer destruction, overcoming hypoxia existing in majority of solid tumors is important for optimizing PDT efficacy...
March 22, 2018: Nano Letters
https://www.readbyqxmd.com/read/29556048/combining-immune-check-point-blockade-and-cryoablation-in-an-immunocompetent-hormone-sensitive-murine-model-of-prostate-cancer
#5
Benjamin Benzon, Stephanie A Glavaris, Brian W Simons, Robert M Hughes, Kamyar Ghabili, Patrick Mullane, Rebecca Miller, Katriana Nugent, Brian Shinder, Jeffrey Tosoian, Ephraim J Fuchs, Phuoc T Tran, Paula J Hurley, Milena Vuica-Ross, Edward M Schaeffer, Charles G Drake, Ashley E Ross
BACKGROUND: Prostate cancer remains the second leading cause of cancer related death in men. Immune check point blocking antibodies have revolutionized treatment of multiple solid tumors, but results in prostate cancer remain marginal. Previous reports have suggested that local therapies, in particular cryoablation might increase tumor immunogenicity. In this work, we examine potential synergism between tumor cryoabalation and check point blocking antibodies. METHODS: FVB/NJ mice were injected subcutaneously into each flank with either 1 × 106 or 0...
April 2018: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/29526974/adjuvant-immunotherapy-for-cancer-both-dendritic-cell-priming-and-check-point-inhibitor-blockade-are-required-for-immunotherapy
#6
Tsukasa Seya, Yohei Takeda, Ken Takashima, Sumito Yoshida, Masahiro Azuma, Misako Matsumoto
The immune system eliminates advanced cancer when treated with programmed cell death protein-1 (PD-1) or its ligand (PD-L1) blockade, but PD-1 therapy is effective in only ∼20% of patients with solid cancer. The PD-1 antibody mainly acts on the effector phase of cytotoxic T lymphocytes (CTLs) in tumors but induces no activation of the priming phase of antigen-presenting dendritic cells (DCs). It is reasonable that both DC-priming and PD-1/L1 blocking are mandatory for efficient CTL-mediated tumor cytolysis...
2018: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
https://www.readbyqxmd.com/read/29361915/neuromyelitis-optica-spectrum-disorder-secondary-to-treatment-with-anti-pd-1-antibody-nivolumab-the-first-report
#7
Yoshitsugu Narumi, Ryohei Yoshida, Yoshinori Minami, Yasushi Yamamoto, Shiori Takeguchi, Kohei Kano, Kae Takahashi, Tsukasa Saito, Jun Sawada, Hiroya Terui, Takayuki Katayama, Takaaki Sasaki, Yoshinobu Ohsaki
BACKGROUND: Immune checkpoint blockade is developed as standard treatment for non-small cell lung cancer. However immune-related adverse events (irAE) have still unknown complications. Here, we report a patient with lung squamous cell carcinoma who developed neuromyelitis optica spectrum disorder with nivolumab. CASE PRESENTATION: A 75-year-old Japanese man with lung squamous cell carcinoma was administered nivolumab as second-line treatment. Two months after treatment with nivolumab, he presented acute paralysis in the bilateral lower limbs, sensory loss...
January 24, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29045560/inflammatory-gastrointestinal-diseases-associated-with-pd-1-blockade-antibodies
#8
M Collins, J M Michot, F X Danlos, C Mussini, E Soularue, C Mateus, D Loirat, A Buisson, I Rosa, O Lambotte, S Laghouati, N Chaput, C Coutzac, A L Voisin, J C Soria, A Marabelle, S Champiat, C Robert, F Carbonnel
Background: Immune check-point blockade agents have shown clinical activity in cancer patients but are associated with immune-related adverse events that could limit their development. The aim of this study was to describe the gastrointestinal immune-related adverse events (GI-irAE) in patients with cancer treated with anti-PD-1. Methods: this is a retrospective study of consecutive adult patients who had a suspected GI-irAE due to anti-PD-1 antibodies between 2013 and 2016...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29026068/hollow-mno-2-as-a-tumor-microenvironment-responsive-biodegradable-nano-platform-for-combination-therapy-favoring-antitumor-immune-responses
#9
Guangbao Yang, Ligeng Xu, Yu Chao, Jun Xu, Xiaoqi Sun, Yifan Wu, Rui Peng, Zhuang Liu
Herein, an intelligent biodegradable hollow manganese dioxide (H-MnO2 ) nano-platform is developed for not only tumor microenvironment (TME)-specific imaging and on-demand drug release, but also modulation of hypoxic TME to enhance cancer therapy, resulting in comprehensive effects favoring anti-tumor immune responses. With hollow structures, H-MnO2 nanoshells post modification with polyethylene glycol (PEG) could be co-loaded with a photodynamic agent chlorine e6 (Ce6), and a chemotherapy drug doxorubicin (DOX)...
October 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28929192/role-of-pd-1-in-immunity-and-diseases
#10
Kenji Chamoto, Muna Al-Habsi, Tasuku Honjo
Immunity developed to defend our bodies from foreign particles, including bacteria and viruses. Although effector cells responsible for acquired immunity, mainly T cells, and B cells, are able to distinguish self from non-self, they sometimes attack the body's tissues because of imperfect central tolerance. Several immune check points developed to limit overactivation of these cells. One of the most important immune checkpoints is programmed cell death-1 (PD-1), which is expressed mainly on activated lymphocytes...
2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28865357/check-point-inhibitors-as-therapies-for-infectious-diseases
#11
REVIEW
Maureen A Cox, Robert Nechanitzky, Tak W Mak
The recent successes of immune check point targeting therapies in treating cancer patients has driven a resurgence of interest in targeting these pathways in chronically infected patients. While still in early stages, basic and clinical data suggest that blockade of CTLA-4 and PD-1 can be beneficial in the treatment of chronic HIV, HBV, and HCV infection, as well as other chronic maladies. Furthermore, novel inhibitory receptors such as Tim-3, LAG-3, and TIGIT are the potential next wave of check points that can be manipulated for the treatment of chronic infection...
October 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28627792/%C3%AE-catenin-in-desmoid-type-fibromatosis-deep-insights-into-the-role-of-t41a-and-s45f-mutations-on-protein-structure-and-gene-expression
#12
Chiara Colombo, Antonino Belfiore, Nicholas Paielli, Loris De Cecco, Silvana Canevari, Erik Laurini, Maurizio Fermeglia, Sabrina Pricl, Paolo Verderio, Stefano Bottelli, Marco Fiore, Silvia Stacchiotti, Elena Palassini, Alessandro Gronchi, Silvana Pilotti, Federica Perrone
Desmoid-type fibromatosis (DF) is a rare mesenchymal lesion with high risk of local recurrence. Specific β-catenin mutations (S45F) appeared to be related to this higher risk compared to T41A-mutated or wild-type (WT). We explored the influence of both mutations and WT on structure stability and affinity of β-catenin for α-catenin and the pattern of gene expression that may influence DF behavior. Using 33 surgically resected primary DFs harboring T41A (n = 14), S45F (n = 10), or WT (n = 9), we performed a comparative molecular analysis by protein/protein interaction modeling, gene expression by DASL microarrays, human inflammation gene panel, and assessment of immune system-based biomarkers by immunohistochemistry...
November 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28470464/expanding-diversity-and-common-goal-of-regulatory-t-and-b-cells-ii-in-allergy-malignancy-and-transplantation
#13
REVIEW
Grażyna Korczak-Kowalska, Anna Stelmaszczyk-Emmel, Katarzyna Bocian, Ewelina Kiernozek, Nadzieja Drela, Joanna Domagała-Kulawik
Regulation of immune response was found to play an important role in the course of many diseases such as autoimmune diseases, allergy, malignancy, organ transplantation. The studies on immune regulation focus on the role of regulatory cells (Tregs, Bregs, regulatory myeloid cells) in these disorders. The number and function of Tregs may serve as a marker of disease activity. As in allergy, the depletion of Tregs is observed and the results of allergen-specific immunotherapy could be measured by an increase in the population of IL-10+ regulatory cells...
December 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28405527/jak-stat-mediated-chronic-inflammation-impairs-cytotoxic-t-lymphocyte-activation-to-decrease-anti-pd-1-immunotherapy-efficacy-in-pancreatic-cancer
#14
Chunwan Lu, Asif Talukder, Natasha M Savage, Nagendra Singh, Kebin Liu
Human pancreatic cancer does not respond to immune check point blockade immunotherapy. One key feature of pancreatic cancer is the association between its progression and chronic inflammation. Emerging evidence supports a key role for the JAK-STAT pathway in pancreatic cancer inflammation. We aimed at testing the hypothesis that sustained JAK-STAT signaling suppresses cytotoxic T lymphocyte (CTL) activation to counteract anti-PD-1 immunotherapy-induced CTL activity in pancreatic cancer. We show that human pancreatic carcinomas express high level of PD-L1 and exhibit low level of CTL infiltration...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28363334/novel-immune-check-point-inhibiting-antibodies-in-cancer-therapy-opportunities-and-challenges
#15
REVIEW
Yael Diesendruck, Itai Benhar
Drug resistance of tumor cells to chemotherapy is limiting the therapeutic efficacy of most anticancer drugs and represents a major obstacle in medical oncology. However, treatment of various human malignancies with biologics, mostly monoclonal antibodies (mAbs), is not limited by such chemoresistance mechanisms. However, other resistance or evasion mechanisms limit the efficacy to anticancer therapeutic mAbs that engage tumor-associated antigens on the surface of the malignant cells. Immune checkpoint blocking monoclonal antibodies are heralded as a promising therapeutic approach in clinical oncology...
January 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/28351171/releasing-the-brake-safety-profile-of-immune-check-point-inhibitors-in-non-small-cell-lung-cancer
#16
REVIEW
Carlo Genova, Giovanni Rossi, Erika Rijavec, Federica Biello, Giulia Barletta, Marco Tagliamento, Francesco Grossi
Immune check-point inhibitors are now employed as single-agents in current practice for the treatment of advanced non-small cell lung cancer (NSCLC), while combinations of different inhibitors are being evaluated in clinical trials. Although the safety profile of these compounds, with particular reference to drugs targeting programmed death protein 1 (PD-1) and its ligand (PD-L1), is generally considered manageable, peculiar, immune-related toxicities may onset. Areas covered: This review focuses on the immune-related adverse events (irAEs) observed during immune check-point blockade in NSCLC and their management...
May 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28259300/immunotherapy-for-the-treatment-of-multiple-myeloma
#17
REVIEW
Sung-Hoon Jung, Hyun-Ju Lee, Manh-Cuong Vo, Hyeoung-Joon Kim, Je-Jung Lee
Immunotherapy has recently emerged as a promising treatment for multiple myeloma (MM). There are now several monoclonal antibodies that target specific surface antigens on myeloma cells or the checkpoints of immune and myeloma cells. Elotuzumab (targeting SLAMF7), daratumumab (targeting CD38), and pembrolizumab (targeting PD-1) have shown clinical activity in clinical studies with relapsed/refractory MM. Dendritic cell vaccination is a safe strategy that has shown some efficacy in a subset of myeloma patients and may become a crucial part of MM treatment when combined with immunomodulatory drugs or immune check-point blockade...
March 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28258697/tim-3-and-its-role-in-regulating-anti-tumor-immunity
#18
REVIEW
Madhumita Das, Chen Zhu, Vijay K Kuchroo
Immunotherapy is being increasingly recognized as a key therapeutic modality to treat cancer and represents one of the most exciting treatments for the disease. Fighting cancer with immunotherapy has revolutionized treatment for some patients and therapies targeting the immune checkpoint molecules such as CTLA-4 and PD-1 have achieved durable responses in melanoma, renal cancer, Hodgkin's diseases and lung cancer. However, the success rate of these treatments has been low and a large number of cancers, including colorectal cancer remain largely refractory to CTLA-4 and PD-1 blockade...
March 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28243590/second-line-treatment-of-nsclc-the-pan-erbb-inhibitor-afatinib-in-times-of-shifting-paradigms
#19
REVIEW
Jens Köhler
In contrast to the established role of epidermal growth factor receptor (EGFR) inhibitors for the first-line treatment of patients with non-small cell lung cancer (NSCLC) harboring activating EGFR mutations, the role of EGFR blockade and of EGFR molecular testing in the second-line treatment remains less clear. The irreversible pan-ErbB family inhibitor afatinib (Gi(l)otrif(®)) was recently FDA- and EMA-approved for the second-line treatment of NSCLC with squamous cell histology irrespective of the EGFR mutational status (LUX-Lung 8)...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28098061/prostate-cancer-immunotherapy-particularly-in-combination-with-androgen-deprivation-or-radiation-treatment-customized-pharmacogenomic-approaches-to-overcome-immunotherapy-cancer-resistance
#20
REVIEW
C Alberti
Conventional therapeutic approaches for advanced prostate cancer - such as androgen deprivation, chemotherapy, radiation - come up often against lack of effectiveness because of possible arising of correlative cancer cell resistance and/or inadequate anti-tumor immune conditions. Whence the timeliness of resorting to immune-based treatment strategies including either therapeutic vaccination-based active immunotherapy or anti-tumor monoclonal antibody-mediated passive immunotherapy. Particularly attractive, as for research studies and clinical applications, results to be the cytotoxic T-lymphocyte check point blockade by the use of anti-CTLA-4 and PD-1 monoclonal antibodies, particularly when combined with androgen deprivation therapy or radiation...
September 2017: Il Giornale di Chirurgia
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