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Checkpoint blockade

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https://www.readbyqxmd.com/read/29786888/injectable-bioresponsive-gel-depot-for-enhanced-immune-checkpoint-blockade
#1
Shuangjiang Yu, Chao Wang, Jicheng Yu, Jinqiang Wang, Yue Lu, Yuqi Zhang, Xudong Zhang, Quanyin Hu, Wujin Sun, Chaoliang He, Xuesi Chen, Zhen Gu
Although cancer immunotherapy based on immune checkpoint inhibitors holds great promise toward many types of cancers, several challenges still remain, associated with low objective response of patient rate as well as systemic side effects. Here, a combination immunotherapy strategy is developed based on a thermogelling reactive oxygen species (ROS)-responsive polypeptide gel for sustained release of anti-programmed cell death-ligand 1 antibody and dextro-1-methyl tryptophan, inhibitor of indoleamine-2,3-dioxygenase with leveraging the ROS level in the tumor microenvironment...
May 22, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29777794/regulatory-t-cell-targeted-hybrid-nanoparticles-combined-with-immuno-checkpoint-blockage-for-cancer-immunotherapy
#2
Wenquan Ou, Raj Kumar Thapa, Liyuan Jiang, Soe Zar Chi, Milan Gautam, Jae-Hoon Chang, Jee-Heon Jeong, Sae Kwang Ku, Han-Gon Choi, Chul Soon Yong, Jong Oh Kim
Immunosuppression in tumor microenvironments induced by regulatory T (Treg) cells is regarded a critical mechanism of tumor immune escape and poses a major impediment to cancer immunotherapy. In this study, we developed tLyp1 peptide-conjugated hybrid nanoparticles for targeting Treg cells in the tumor microenvironment. The tLyp1 peptide-modified hybrid nanoparticles presented good stability and effective targeting to Treg cells, and they enhanced the effect of imatinib in downregulating Treg cell suppression through inhibition of STAT3 and STAT5 phosphorylation...
May 16, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29775845/toward-innovative-combinational-immunotherapy-a-systems-biology-perspective
#3
REVIEW
Xue-Tao Li, Jin-Ji Yang, Yi-Long Wu, Jun Hou
The treatment of non-small-cell lung cancer (NSCLC) has advanced significantly in the last decades. Especially immune checkpoint inhibitors have shown inconceivable effect on enhancing host anti-tumor activity in NSCLC. However, the limitation of checkpoint blockade monotherapy seems unavoidable in most of the NSCLC patients and only ∼20% of them achieved response to monotherapy with immune checkpoint inhibitors. Thus combining immune checkpoint inhibitors with other agents with different action mechanisms holds a promise to revitalize NSCLC treatment, such as the combination of checkpoint inhibitors with angiogenesis inhibitors, or with chemotherapy, as well as the combination of two checkpoint inhibitors...
May 8, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29774123/the-association-of-human-endogenous-retrovirus-h-long-terminal-repeat-associating-protein-2-hhla2-expression-with-gastric-cancer-prognosis
#4
Masataka Shimonosono, Takaaki Arigami, Shigehiro Yanagita, Daisuke Matsushita, Yasuto Uchikado, Yuko Kijima, Hiroshi Kurahara, Yoshiaki Kita, Shinichiro Mori, Ken Sasaki, Itaru Omoto, Kosei Maemura, Yoshikazu Uenosono, Sumiya Ishigami, Shoji Natsugoe
Currently, immune checkpoint blockade against members of the B7/CD28 family is being used as a new molecular-targeted therapy, in patients with unresectable advanced or recurrent gastric cancer. Although human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) is a novel molecule of the B7/CD28 family, the clinical impact of its expression remains uncertain in gastric cancer. Consequently, we examined HHLA2 expression in blood specimens from patients with gastric cancer, and investigated the relationship between its expression and clinicopathological factors to assess its potential power as a prognostic blood predictor...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29771686/spleen-mediates-a-distinct-hematopoietic-progenitor-response-supporting-tumor-promoting-myelopoiesis
#5
Chong Wu, Huiheng Ning, Mingyu Liu, Jie Lin, Shufeng Luo, Wenjie Zhu, Jing Xu, Wen-Chao Wu, Jing Liang, Chun-Kui Shao, Jiaqi Ren, Bin Wei, Jun Cui, Min-Shan Chen, Limin Zheng
Cancer progression is associated with alterations of intra- and extramedullary hematopoiesis to support a systemic tumor-promoting myeloid response. However, the functional specialty, mechanism, and clinical relevance of extramedullary hematopoiesis (EMH) remain unclear. Here we showed that the heightened splenic myelopoiesis in tumor-bearing hosts was not only characterized by the accumulation of myeloid precursors, but also associated with profound functional alterations of splenic early hematopoietic stem/progenitor cells (HSPCs)...
May 17, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29771487/cancer-cell-membrane-coated-adjuvant-nanoparticles-with-mannose-modification-for-effective-anticancer-vaccination
#6
Rong Yang, Jun Xu, Ligeng Xu, Xiaoqi Sun, Qian Chen, Yuhuan Zhao, Rui Peng, Zhuang Liu
Tumor vaccines for cancer prevention and treatment have attracted tremendous interests in the area of cancer immunotherapy in recent years. In this work, we present a strategy to construct cancer vaccines by encapsulating immune-adjuvant nanoparticles with cancer cell membrane modified by mannose. Poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles are firstly loaded with toll-like receptor 7 agonist, imiquimod (R837). Those adjuvant nanoparticles (NP-R) are then coated with cancer cell membranes (NP-R@M), whose surface proteins could act as tumor-specific antigens...
May 17, 2018: ACS Nano
https://www.readbyqxmd.com/read/29770915/cytolytic-activity-score-to-assess-anticancer-immunity-in-colorectal-cancer
#7
Sumana Narayanan, Tsutomu Kawaguchi, Li Yan, Xuan Peng, Qianya Qi, Kazuaki Takabe
BACKGROUND: Elevated tumor-infiltrating lymphocytes (TILs) within the tumor microenvironment is a known positive prognostic factor in colorectal cancer (CRC). We hypothesized that since cytotoxic T cells release cytolytic proteins such as perforin (PRF1) and pro-apoptotic granzymes (GZMA) to attack cancer cells, a cytolytic activity score (CYT) would be a useful tool to assess anticancer immunity. METHODS: Genomic expression data were obtained from 456 patients from The Cancer Genome Atlas (TCGA)...
May 16, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29769722/bystander-cd8-t-cells-are-abundant-and-phenotypically-distinct-in-human-tumour-infiltrates
#8
Yannick Simoni, Etienne Becht, Michael Fehlings, Chiew Yee Loh, Si-Lin Koo, Karen Wei Weng Teng, Joe Poh Sheng Yeong, Rahul Nahar, Tong Zhang, Hassen Kared, Kaibo Duan, Nicholas Ang, Michael Poidinger, Yin Yeng Lee, Anis Larbi, Alexis J Khng, Emile Tan, Cherylin Fu, Ronnie Mathew, Melissa Teo, Wan Teck Lim, Chee Keong Toh, Boon-Hean Ong, Tina Koh, Axel M Hillmer, Angela Takano, Tony Kiat Hon Lim, Eng Huat Tan, Weiwei Zhai, Daniel S W Tan, Iain Beehuat Tan, Evan W Newell
Various forms of immunotherapy, such as checkpoint blockade immunotherapy, are proving to be effective at restoring T cell-mediated immune responses that can lead to marked and sustained clinical responses, but only in some patients and cancer types1-4 . Patients and tumours may respond unpredictably to immunotherapy partly owing to heterogeneity of the immune composition and phenotypic profiles of tumour-infiltrating lymphocytes (TILs) within individual tumours and between patients5,6 . Although there is evidence that tumour-mutation-derived neoantigen-specific T cells play a role in tumour control2,4,7-10 , in most cases the antigen specificities of phenotypically diverse tumour-infiltrating T cells are largely unknown...
May 16, 2018: Nature
https://www.readbyqxmd.com/read/29769207/mitigating-sox2-potentiated-immune-escape-of-head-and-neck-squamous-cell-carcinoma-with-a-sting-inducing-nanosatellite-vaccine
#9
Yee Sun Tan, Kanokwan Sansanaphongpricha, Yuying Xie, Christopher R Donnelly, Xiaobo Luo, Blake R Heath, Xinyi Zhao, Emily L Bellile, Hongxiang Hu, Hongwei Chen, Peter J Polverini, Qianming Chen, Simon Young, Thomas E Carey, Jacques E Nör, Robert L Ferris, Gregory Wolf, Duxin Sun, Yu L Lei
PURPOSE: The response rates of Head and Neck Squamous Cell Carcinoma (HNSCC) to checkpoint blockade are below 20%. We aim to develop a mechanism-based vaccine to prevent HNSCC immune escape. EXPERIMENTAL DESIGN: We performed RNA-Seq of sensitive and resistant HNSCC cells to discover central pathways promoting resistance to immune killing. Using biochemistry, animal models, HNSCC microarray and immune cell deconvolution, we assessed the role of SOX2 in inhibiting STING-type I interferon (IFN-I) signaling-mediated anti-tumor immunity...
May 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29769148/current-landscape-and-future-of-dual-anti-ctla4-and-pd-1-pd-l1-blockade-immunotherapy-in-cancer-lessons-learned-from-clinical-trials-with-melanoma-and-non-small-cell-lung-cancer-nsclc
#10
REVIEW
Young Kwang Chae, Ayush Arya, Wade Iams, Marcelo R Cruz, Sunandana Chandra, Jaehyuk Choi, Francis Giles
Immunotherapy is among the most rapidly evolving treatment strategies in oncology. The therapeutic potential of immune-checkpoint inhibitors is exemplified by the recent hail of Food and Drug Administration (FDA) approvals for their use in various malignancies. Continued efforts to enhance outcomes with immunotherapy agents have led to the formulation of advanced treatment strategies. Recent evidence from pre-clinical studies evaluating immune-checkpoint inhibitors in various cancer cell-lines has suggested that combinatorial approaches may have superior survival outcomes compared to single-agent immunotherapy regimens...
May 16, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29764164/immunoregulatory-antigens-novel-targets-for-cancer-immunotherapy
#11
Ayako Wakatsuki Pedersen, Katharina L Kopp, Mads Hald Andersen, Mai-Britt Zocca
Historically, the development of cancer vaccines has focused on the central role of tumor antigens in eliciting tumor-specific immune responses, with limited success. Recent advances with checkpoint blockade approaches have brought about a renewed appreciation of the importance of targeting immune suppression in cancer patients. Here we discuss a novel approach to cancer immunotherapy, namely to target recently described T cells that uniquely control cells with immune suppressive functions. Accumulating evidence support the existence of self-reactive T cells that are specific to antigens derived from immunoregulatory proteins ("immunoregulatory antigens"), such as indoleamine 2,3-dioxygenase (IDO) and PD-L1...
April 2018: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29764160/combinatorial-strategies-of-radiotherapy-and-immunotherapy-in-nasopharyngeal-carcinoma
#12
Eugenia L L Yeo, You Quan Li, Khee-Chee Soo, Joseph T S Wee, Melvin L K Chua
Immunotherapy and radiation therapy (RT) have each demonstrated clinical success in the treatment of nasopharyngeal carcinoma (NPC) when utilized independently. Several characteristics of NPC make it particularly well suited for immunotherapeutic strategies, such as the association with viral infections like EBV and human papilloma virus (HPV), upregulation of PD-L1 expression, and the high number of tumor infiltrating lymphocytes. Immune checkpoint blockade is one such immunotherapeutic strategy that is gaining popularity rapidly...
April 2018: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29762866/obesity-as-an-immune-modifying-factor-in-cancer-immunotherapy
#13
REVIEW
Robert J Canter, Catherine T Le, Johanna M T Beerthuijzen, William J Murphy
Immunotherapy has achieved breakthrough status in many advanced stage malignancies and is rapidly becoming the fourth arm of cancer treatment. Although cancer immunotherapy has generated significant excitement because of the potential for complete and sometimes durable responses, there is also the potential for severe and occasionally life-threatening toxicities, including cytokine release syndrome and severe autoimmunity. A large body of work also points to a "metainflammatory" state in obesity associated with impairment of immune responses...
May 15, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29762727/development-of-targeted-therapy-and-immunotherapy-for-treatment-of-small-cell-lung-cancer
#14
Motonobu Saito, Kouya Shiraishi, Akiteru Goto, Hiroyuki Suzuki, Takashi Kohno, Koji Kono
Targeted therapy against druggable genetic aberrations has shown a significantly positive response rate and longer survival in various cancers, including lung cancer. In lung adenocarcinoma (LADC), specific thyroxin kinase inhibitors against EGFR mutations and ALK fusions are used as a standard treatment regimen and show significant positive efficacy. On the other hand, targeted therapy against driver gene aberrations has not been adapted yet in small cell lung cancer (SCLC). This is because driver genes and druggable aberrations are rarely identified by next generation sequencing in SCLC...
May 14, 2018: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29760047/nanoparticles-that-reshape-the-tumor-milieu-create-a-therapeutic-window-for-effective-t-cell-therapy-in-solid-malignancies
#15
Fan Zhang, Sirkka B Stephan, Chibawanye I Ene, Tyrel T Smith, Eric C Holland, Matthias T Stephan
A major obstacle to the success rate of chimeric antigen receptor (CAR-) T cell therapy against solid tumors is the microenvironment antagonistic to T cells that solid tumors create. Conventional checkpoint blockade can silence lymphocyte anti-survival pathways activated by tumors, but because they are systemic, these treatments disrupt immune homeostasis and induce autoimmune side effects. Thus, new technologies are required to remodel the tumor milieu without causing systemic toxicities. Here we demonstrate that targeted nanocarriers that deliver a combination of immune-modulatory agents can remove pro-tumor cell populations and simultaneously stimulate anti-tumor effector cells...
May 14, 2018: Cancer Research
https://www.readbyqxmd.com/read/29757416/early-changes-in-cd4-t-cell-activation-following-blood-stage-plasmodium-falciparum-infection
#16
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/29756564/clinical-and-pharmacologic-features-of-monoclonal-antibodies-and-checkpoint-blockade-therapy-in-multiple-myeloma
#17
Mattia D'Agostino, Giulia Gazzera, Giusy Cetani, Sara Bringhen, Mario Boccadoro, Francesca Gay
BACKGROUND: Survival of multiple myeloma patients has considerably improved in the last decades thanks to the introduction of many new drugs, including immunomodulatory agents, proteasome inhibitors and, more recently, monoclonal antibodies. METHODS: We analyzed the most recent literature focusing on the clinical and pharmacologic aspects of monoclonal antibody-based therapies in multiple myeloma, including monoclonal antibodies directed against plasma cell antigens, as well as checkpoint blockade therapy directed against immune inhibitory molecules, used as single agents or in combination therapy...
May 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29755681/dendritic-cell-activation-enhances-anti-pd-1-mediated-immunotherapy-against-glioblastoma
#18
Tomas Garzon-Muvdi, Debebe Theodros, Andrew S Luksik, Russell Maxwell, Eileen Kim, Christopher M Jackson, Zineb Belcaid, Sudipto Ganguly, Betty Tyler, Henry Brem, Drew M Pardoll, Michael Lim
Introduction: The glioblastoma (GBM) immune microenvironment is highly suppressive as it targets and hinders multiple components of the immune system. Checkpoint blockade (CB) is being evaluated for GBM patients. However, biomarker analyses suggest that CB monotherapy may be effective only in a small fraction of GBM patients. We hypothesized that activation of antigen presentation would increase the therapeutic response to PD-1 blockade. Results: We show that activating DCs through TLR3 agonists enhances the anti-tumor immune response to CB and increases survival in GBM...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29752295/-arid1a-deficiency-may-predict-response-to-immune-checkpoint-blockade
#19
(no author information available yet)
ARID1A deficiency impairs mismatch repair to increase tumor mutation load and promote tumor progression.
May 11, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29751996/update-on-tumor-neoantigens-and-their-utility-why-it-is-good-to-be-different
#20
REVIEW
Chung-Han Lee, Roman Yelensky, Karin Jooss, Timothy A Chan
Antitumor rejection by the immune system is a complex process that is regulated by several factors. Among these factors are the quality and quantity of mutational events that occur in cancer cells. Perhaps one of the most important types of mutations that influence antitumor immunity is the neoantigen, that is, a non-self-antigen that arises as a result of somatic mutation. Recent work has demonstrated that neoantigens hold significant promise for developing new diagnostic and therapeutic modalities. Therapeutic targeting of neoantigens is important for achieving benefit following therapy with immune checkpoint blockade agents or for cancer vaccines targeting mutations...
May 8, 2018: Trends in Immunology
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