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Cancer Immunology, Immunotherapy: CII

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https://www.readbyqxmd.com/read/28638976/lilrb-receptor-mediated-regulation-of-myeloid-cell-maturation-and-function
#1
REVIEW
William van der Touw, Hui-Ming Chen, Ping-Ying Pan, Shu-Hsia Chen
The leukocyte immunoglobulin-like receptor (LILR) family comprises a set of paired immunomodulatory receptors expressed among human myeloid and lymphocyte cell populations. While six members of LILR subfamily A (LILRA) associate with membrane adaptors to signal via immunoreceptor tyrosine-based activating motifs (ITAM), LILR subfamily B (LILRB) members signal via multiple cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIM). Ligand specificity of some LILR family members has been studied in detail, but new perspective into the immunoregulatory aspects of this receptor family in human myeloid cells has been limited...
June 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28634816/critical-biological-parameters-modulate-affinity-as-a-determinant-of-function-in-t-cell-receptor-gene-modified-t-cells
#2
Timothy T Spear, Yuan Wang, Kendra C Foley, David C Murray, Gina M Scurti, Patricia E Simms, Elizabeth Garrett-Mayer, Lance M Hellman, Brian M Baker, Michael I Nishimura
T-cell receptor (TCR)-pMHC affinity has been generally accepted to be the most important factor dictating antigen recognition in gene-modified T-cells. As such, there is great interest in optimizing TCR-based immunotherapies by enhancing TCR affinity to augment the therapeutic benefit of TCR gene-modified T-cells in cancer patients. However, recent clinical trials using affinity-enhanced TCRs in adoptive cell transfer (ACT) have observed unintended and serious adverse events, including death, attributed to unpredicted off-tumor or off-target cross-reactivity...
June 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28634815/autoimmune-diabetes-induced-by-pd-1-inhibitor-retrospective-analysis-and-pathogenesis-a-case-report-and-literature-review
#3
Marie-Léa Gauci, Pauline Laly, Tiphaine Vidal-Trecan, Barouyr Baroudjian, Jérémy Gottlieb, Nika Madjlessi-Ezra, Laetitia Da Meda, Isabelle Madelaine-Chambrin, Martine Bagot, Nicole Basset-Seguin, Cécile Pages, Samia Mourah, Philippe Boudou, Céleste Lebbé, Jean-François Gautier
Anti-PD-1 antibody treatment is approved in advanced melanoma and provides median overall survival over 24 months. The main treatment-related side effects are immune-related adverse events, which include rash, pruritus, vitiligo, thyroiditis, diarrhoea, hepatitis and pneumonitis. We report a case of autoimmune diabetes related to nivolumab treatment. A 73-year-old man was treated in second line with nivolumab at 3 mg/kg every two weeks for metastatic melanoma. At 6 weeks of treatment, he displayed diabetic ketoacidosis...
June 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28623459/blockade-of-cd112r-and-tigit-signaling-sensitizes-human-natural-killer-cell-functions
#4
Feng Xu, Alexander Sunderland, Yue Zhou, Richard D Schulick, Barish H Edil, Yuwen Zhu
Trastuzumab is the first-line drug to treat breast cancer with high Her2 expression. However, many cancers failed to respond, largely due to their resistance to NK cell-triggered antibody-dependent cellular cytotoxicity (ADCC). Poliovirus receptor (PVR)-like molecules are known to be important for lymphocyte functions. We found that all PVR-like receptors are expressed on human NK cells, and only TIGIT is preferentially expressed on the CD16+ NK cell subset. Disrupting the interactions of PVR-like receptors with their ligands on cancer cells regulates NK cell activity...
June 16, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28612140/a-phase-ii-study-of-ipilimumab-plus-temozolomide-in-patients-with-metastatic-melanoma
#5
Sapna P Patel, Dae Won Kim, Roland L Bassett, Suzanne Cain, Edwina Washington, Wen-Jen Hwu, Kevin B Kim, Nicholas E Papadopoulos, Jade Homsi, Patrick Hwu, Agop Y Bedikian
Checkpoint blockade has revolutionized the treatment of melanoma; however, it benefits only the minority of patients. Several agents have been combined with immunotherapy to improve T-cell activation and persistence including growth factor, chemotherapy, and radiation. Preclinical data suggest that temozolomide, which metabolizes to the same active compound as dacarbazine, selectively depletes regulatory T cells. This potential immunomodulatory effect of temozolomide provides rationale for combination with ipilimumab...
June 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28608115/phase-i-trial-of-antigen-targeted-autologous-dendritic-cell-based-vaccine-with-in-vivo-activation-of-inducible-cd40-for-advanced-prostate-cancer
#6
Guru Sonpavde, John D McMannis, Yu Bai, Mamatha R Seethammagari, Joan M C Bull, Victoria Hawkins, Theresa K Dancsak, Natasha Lapteva, Jonathan M Levitt, Annemarie Moseley, David M Spencer, Kevin M Slawin
This phase I trial reports the safety and activity of BPX101, a second-generation antigen-targeted autologous antigen presenting cell (APC) vaccine in men with metastatic castration-resistant prostate cancer (mCRPC). To manufacture BPX101, APCs collected in a single leukapheresis were transduced with adenoviral vector Ad5f35 encoding inducible human (ih)-CD40, followed by incubation with protein PA001, which contains the extracellular domain of human prostate-specific membrane antigen. The ih-CD40 represents a modified chimeric version of the dendritic cell (DC) co-stimulatory molecule, CD40, which responds to a bioinert membrane-permeable activating dimerizer drug, rimiducid (AP1903), permitting temporally controlled, lymphoid-localized, DC-specific activation...
June 12, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28601925/enhanced-stimulation-of-human-tumor-specific-t-cells-by-dendritic-cells-matured-in-the-presence-of-interferon-%C3%AE-and-multiple-toll-like-receptor-agonists
#7
Tanja Lövgren, Dhifaf Sarhan, Iva Truxová, Bhavesh Choudhary, Roeltje Maas, Jeroen Melief, Maria Nyström, Ulrika Edbäck, Renee Vermeij, Gina Scurti, Michael Nishimura, Giuseppe Masucci, Alex Karlsson-Parra, Andreas Lundqvist, Lars Adamson, Rolf Kiessling
Dendritic cell (DC) vaccines have been demonstrated to elicit immunological responses in numerous cancer immunotherapy trials. However, long-lasting clinical effects are infrequent. We therefore sought to establish a protocol to generate DC with greater immunostimulatory capacity. Immature DC were generated from healthy donor monocytes by culturing in the presence of IL-4 and GM-CSF and were further differentiated into mature DC by the addition of cocktails containing different cytokines and toll-like receptor (TLR) agonists...
June 10, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28601924/tgf-%C3%AE-1-silenced-leukemia-cell-derived-exosomes-target-dendritic-cells-to-induce-potent-anti-leukemic-immunity-in-a-mouse-model
#8
Fang Huang, Jiangbo Wan, Siguo Hao, Xiaohui Deng, Linjun Chen, Liyuan Ma
Tumor-derived exosomes (TEX) can induce a specific antitumor immune response and have been developed as a promising tumor vaccine. Despite promising preclinical data, TEX exhibit relatively low efficacy and limited clinical benefit in clinical trials. In the present study, we investigated whether exosomes from the TGF-β1 silenced L1210 cells (LEXTGF-β1si) can enhance the efficacy of DC-based vaccines. We silenced TGF-β1 in L1210 cells with a lentiviral shRNA vector and prepared the LEXTGF-β1si. It was shown that LEXTGF-β1si can significantly decrease TGF-β1 expression of dendritic cells (DC) and effectively promote their maturation and immune function...
June 10, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28577085/endoplasmic-reticulum-stress-regulates-tumor-growth-and-anti-tumor-immunity-a-promising-opportunity-for-cancer-immunotherapy
#9
REVIEW
Eslam Mohamed, Yu Cao, Paulo C Rodriguez
The endoplasmic reticulum (ER) stress is a cellular process that occurs as a consequence of several stress circumstances, such as the accumulation of unfolded proteins in the lumen of the ER or distinct insults that disturb the ER normal function. Different conditions in the tumor microenvironment (TME), including hypoxia, nutrient deprivation, and the elevated production of reactive oxygen and nitrogen species destabilize the loading and dispatching of the newly synthesized proteins, triggering ER stress in cancer cells and tumor-infiltrating leukocytes...
June 2, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28555259/in-vitro-differentiated-plasmacytoid-dendritic-cells-as-a-tool-to-induce-anti-leukemia-activity-of-natural-killer-cells
#10
Yildian Díaz-Rodríguez, Paulo Cordeiro, Assila Belounis, Sabine Herblot, Michel Duval
Acute lymphoblastic leukemia (ALL) is believed to be resistant to NK cell-mediated killing. To overcome this resistance, we developed an innovative approach based on NK cell stimulation with Toll-like receptor (TLR)-activated plasmacytoid dendritic cells (pDC). The translation of this approach into the clinic requires the production of high numbers of human pDC. Herein, we show that in vitro differentiation of cord blood CD34(+) progenitors in the presence of aryl hydrocarbon receptor antagonists gives rise to clinically relevant numbers of pDC, as about 10(8) pDC can be produced from a typical cord blood unit...
May 29, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28555258/peripheral-blood-t-cell-alterations-in-newly-diagnosed-diffuse-large-b-cell-lymphoma-patients-and-their-long-term-dynamics-upon-rituximab-based-chemoimmunotherapy
#11
Simone Battella, M Christina Cox, Raffaella La Scaleia, Arianna Di Napoli, Francesca Di Landro, Alessandra Porzia, Lavinia Franchitti, Fabrizio Mainiero, Luigi Ruco, Bruno Monarca, Angela Santoni, Gabriella Palmieri
The importance of T cell-dependent immune responses in achieving long-term cure of chemoimmunotherapy-treated cancer patients is underscored by the recently described "vaccinal effect" exerted by therapeutic mAbs. In accordance, pre- and post-therapy peripheral blood lymphopenia represents a well-established negative prognostic factor in DLBCL. We analyzed the phenotypic and functional (IFNγ production, and Granzyme B (GrzB) cytotoxic granule marker expression) profile of peripheral blood T lymphocyte subsets ("conventional" CD4(+) and CD8(+), FOXP3(+)CD25(bright) Treg, and "innate-like" CD56(+)) in DLBCL patients at diagnosis, and assessed the long-term impact of R-CHOP chemoimmunotherapy, in a prospective study...
May 29, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28555257/professor-enrico-mihich-1928-2016
#12
EDITORIAL
Graham Pawelec, Suzanne Ostrand-Rosenberg
No abstract text is available yet for this article.
May 29, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28551814/macrophage-derived-interleukin-1beta-promotes-human-breast-cancer-cell-migration-and-lymphatic-adhesion-in-vitro
#13
Sarah J Storr, Sabreena Safuan, Narmeen Ahmad, Mohammed El-Refaee, Andrew M Jackson, Stewart G Martin
Lymphovascular invasion (LVI), encompassing blood and lymphatic vessel invasion, is an important event in tumourigenesis. Macrophages within the tumour microenvironment are linked to the presence of LVI and angiogenesis. This study investigates the role of macrophage-derived, caspase-1-dependent interleukin-1beta (IL-1β) in an in vitro model of LVI. IL-1β significantly augmented the adhesion and transmigration of breast cancer cell lines MCF7 and MDA-MB-231 across endothelial cell barriers. MDA-MB-231 and MCF7 showed a higher percentage of adhesion to lymphatic endothelial cells than blood endothelial cells following endothelial cell IL-1β stimulation (P < 0...
May 27, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28551813/cd45ra-foxp3-high-regulatory-t-cells-have-a-negative-impact-on-the-clinical-outcome-of-head-and-neck-squamous-cell-carcinoma
#14
Fumie Ihara, Daiju Sakurai, Atsushi Horinaka, Yuji Makita, Akira Fujikawa, Toshioki Sakurai, Kazuki Yamasaki, Naoki Kunii, Shinichiro Motohashi, Toshinori Nakayama, Yoshitaka Okamoto
BACKGROUND: Although regulatory T cells (Tregs) are thought to play an important role in immune suppression, their clinical significance in head and neck squamous cell carcinoma (HNSCC) is unclear. A recent study reported Tregs could be divided into functional subsets based on the expression of CD45RA and Foxp3. METHOD: The frequency of circulating Treg subsets was analyzed in patients with HNSCC and compared with the frequency in patients with benign tumors. The association of Treg subsets with the frequency of lymphocyte subsets, status of progression, clinical course, and prognosis were also examined...
May 27, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28540431/a-gene-polymorphism-in-pd-l1-promoter-region-is-not-associated-with-pd-l1-expression-and-patients-survival-in-gastric-cancer
#15
LETTER
Weili Wang, Ping Liao, Yijing He
No abstract text is available yet for this article.
May 24, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28523518/decreased-human-leukocyte-antigen-a-02-01-frequency-is-associated-with-risk-of-glioma-and-existence-of-human-cytomegalovirus-a-case-control-study-in-northern-china
#16
Sheng Han, Jian Deng, Zixun Wang, Huan Liu, Wen Cheng, Anhua Wu
BACKGROUND: Human leukocyte antigens (HLAs) play an important role in host defense against viral infection and tumorigenesis. Human cytomegalovirus (HCMV) has been linked to glioma development. This study investigated the relationship between HLA distribution, presence of HCMV, and glioma development in a Han Chinese population. METHODS: The study population included 150 glioma patients and 150 tumor-free brain injury control subjects (control-A) matched according to geography, ethnicity, age, and gender...
May 18, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28501941/paracrine-release-of-il-2-and-anti-ctla-4-enhances-the-ability-of-artificial-polymer-antigen-presenting-cells-to-expand-antigen-specific-t-cells-and-inhibit-tumor-growth-in-a-mouse-model
#17
Lei Zhang, Limin Wang, Khawar Ali Shahzad, Tao Xu, Xin Wan, Weiya Pei, Chuanlai Shen
Accumulating evidence indicates that bead-based artificial antigen-presenting cells (aAPCs) are a powerful tool to induce antigen-specific T cell responses in vitro and in vivo. To date, most conventional aAPCs have been generated by coupling an antigen signal (signal 1) and one or two costimulatory signals, such as anti-CD28 with anti-LFA1 or anti-4-1BB (signal 2), onto the surfaces of cell-sized or nanoscale magnetic beads or polyester latex beads. The development of a biodegradable scaffold and the combined use of multiple costimulatory signals as well as third signals for putative clinical applications is the next step in the development of this technology...
May 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28501940/common-extracellular-matrix-regulation-of-myeloid-cell-activity-in-the-bone-marrow-and-tumor-microenvironments
#18
REVIEW
Sabina Sangaletti, Claudia Chiodoni, Claudio Tripodo, Mario P Colombo
The complex interaction between cells undergoing transformation and the various stromal and immunological cell components of the tumor microenvironment (TME) crucially influences cancer progression and diversification, as well as endowing clinical and prognostic significance. The immunosuppression characterizing the TME depends on the recruitment and activation of different cell types including regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages. Less considered is the non-cellular component of the TME...
May 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28501939/dianthin-30-or-gelonin-versus-monomethyl-auristatin-e-each-configured-with-an-anti-calcitonin-receptor-antibody-are-differentially-potent-in-vitro-in-high-grade-glioma-cell-lines-derived-from-glioblastoma
#19
Roger Gilabert-Oriol, Sebastian G B Furness, Brett W Stringer, Alexander Weng, Hendrik Fuchs, Bryan W Day, Angela Kourakis, Andrew W Boyd, David L Hare, Mayank Thakur, Terrance G Johns, Peter J Wookey
We have reported that calcitonin receptor (CTR) is widely expressed in biopsies from the lethal brain tumour glioblastoma by malignant glioma and brain tumour-initiating cells (glioma stem cells) using anti-human CTR antibodies. A monoclonal antibody against an epitope within the extracellular domain of CTR was raised (mAb2C4) and chemically conjugated to either plant ribosome-inactivating proteins (RIPs) dianthin-30 or gelonin, or the drug monomethyl auristatin E (MMAE), and purified. In the high-grade glioma cell line (HGG, representing glioma stem cells) SB2b, in the presence of the triterpene glycoside SO1861, the EC50 for mAb2C4:dianthin was 10...
May 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28501938/zoledronic-acid-renders-human-m1-and-m2-macrophages-susceptible-to-v%C3%AE-2-%C3%AE-%C3%AE-t-cell-cytotoxicity-in-a-perforin-dependent-manner
#20
Daniel W Fowler, John Copier, Angus G Dalgleish, Mark D Bodman-Smith
Vδ2(+) T cells are a subpopulation of γδ T cells in humans that are cytotoxic towards cells which accumulate isopentenyl pyrophosphate. The nitrogen-containing bisphosphonate, zoledronic acid (ZA), can induce tumour cell lines to accumulate isopentenyl pyrophosphate, thus rendering them more susceptible to Vδ2(+) T cell cytotoxicity. However, little is known about whether ZA renders other, non-malignant cell types susceptible. In this study we focussed on macrophages (Mϕs), as these cells have been shown to take up ZA...
May 13, 2017: Cancer Immunology, Immunotherapy: CII
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