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Cancer immunotherapy

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https://www.readbyqxmd.com/read/28107662/a-simple-and-powerful-co-delivery-system-based-on-ph-responsive-metal-organic-frameworks-for-enhanced-cancer-immunotherapy
#1
Fei Duan, Xiaochen Feng, Xinjian Yang, Wentong Sun, Yi Jin, Huifang Liu, Kun Ge, Zhenhua Li, Jinchao Zhang
Tumor-associated antigens (TAAs)-loaded nanoparticles are able to be actively internalized by antigen-presenting cells (APCs) and have shown promising potential in cancer immunotherapy. However, current TAAs delivery strategy exhibits limitations of complicated synthesis process, low loading efficiency and inefficient CD8(+) cytotoxic T lymphocyte activation leading to unsatisfactory therapeutic effect. Thus, the construction of novel TAAs-delivery systems for enhanced cancer therapy is highly desirable. In this work, we fabricated a very simple yet powerful antigens-delivery system for cancer immunotherapy based-on pH-responsive metal-organic frameworks (MOFs) with size about 30 nm...
January 11, 2017: Biomaterials
https://www.readbyqxmd.com/read/28107571/increased-pd-l1-expression-in-breast-and-colon-cancer-stem-cells
#2
Yanheng Wu, Mingshui Chen, Peihong Wu, Chen Chen, Zhi Ping Xu, Wenyi Gu
Here we report the expression of programmed cell death ligand 1/2 (PD-L1/L2) in breast and colon cancer stem cells (CSCs). The stemness of these cells was confirmed by their surface markers. Using flow cytometry analysis we demonstrated that PD-L1 expression was higher in CSCs of both cancers compared to non-stem like cancer cells. Consistent with this, detection of cellular PD-L1 proteins by Western blot assay also showed increased PD-L1 protein in CSCs. In contrast, only trance amounts of PD-L2 were detected in CSCs of both cancers...
January 20, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28107186/the-combination-of-pd-l1-expression-and-decreased-tumor-infiltrating-lymphocytes-is-associated-with-a-poor-prognosis-in-triple-negative-breast-cancer
#3
Hitomi Mori, Makoto Kubo, Rin Yamaguchi, Reiki Nishimura, Tomofumi Osako, Nobuyuki Arima, Yasuhiro Okumura, Masayuki Okido, Mai Yamada, Masaya Kai, Junji Kishimoto, Yoshinao Oda, Masafumi Nakamura
This study included patients with primary triple-negative breast cancer (TNBC) who underwent resection without neoadjuvant chemotherapy between January 2004 and December 2014. Among the 248 TNBCs studied, programmed cell death ligand-1 (PD-L1) expression was detected in 103 (41.5%) tumors, and high levels of tumor-infiltrating lymphocytes (TILs) were present in 118 (47.6%) tumors. PD-L1 expression correlated with high levels of TILs, but was not a prognostic factor. Patients with TILs-high tumors had better overall survival than those with TILs-low tumors (P = 0...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28106152/cancer-immunotherapy-immune-checkpoint-blockade-and-associated-endocrinopathies
#4
REVIEW
David J Byun, Jedd D Wolchok, Lynne M Rosenberg, Monica Girotra
Advances in cancer therapy in the past few years include the development of medications that modulate immune checkpoint proteins. Cytotoxic T-lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) are two co-inhibitory receptors that are expressed on activated T cells against which therapeutic blocking antibodies have reached routine clinical use. Immune checkpoint blockade can induce inflammatory adverse effects, termed immune-related adverse events (IRAEs), which resemble autoimmune disease...
January 20, 2017: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/28105694/lack-of-xage-1b-and-ny-eso-1-in-metastatic-lymph-nodes-may-predict-the-potential-survival-of-stage-iii-melanoma-patients
#5
Mariko Mori, Takeru Funakoshi, Kaori Kameyama, Yutaka Kawakami, Eiichi Sato, Eiichi Nakayama, Masayuki Amagai, Keiji Tanese
The cancer-testis antigens (CTA) are a large family of tumor-associated antigens expressed by a variety of cancer cells and primitive germ cells of the adult testis and placenta. These tumor-restricted expressing patterns suggest that CTA would be ideal targets for tumor-specific immunotherapy. XAGE-1 is a CTA that was originally identified by computer-based screening, and four transcription variants, XAGE-1a, -1b, -1c and -1d, have been characterized to date. Although the presence of XAGE-1 transcripts has been reported in various cancers, the expression of XAGE-1b in melanoma has not been fully characterized...
January 20, 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/28105371/unfolding-anti-tumor-immunity-er-stress-responses-sculpt-tolerogenic-myeloid-cells-in-cancer
#6
REVIEW
Juan R Cubillos-Ruiz, Eslam Mohamed, Paulo C Rodriguez
Established tumors build a stressful and hostile microenvironment that blocks the development of protective innate and adaptive immune responses. Different subsets of immunoregulatory myeloid populations, including dendritic cells, myeloid-derived suppressor cells (MDSCs) and macrophages, accumulate in the stressed tumor milieu and represent a major impediment to the success of various forms of cancer immunotherapy. Specific conditions and factors within tumor masses, including hypoxia, nutrient starvation, low pH, and increased levels of free radicals, provoke a state of "endoplasmic reticulum (ER) stress" in both malignant cells and infiltrating myeloid cells...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28105369/potassium-channels-of-t-lymphocytes-take-center-stage-in-the-fight-against-cancer
#7
EDITORIAL
Laura Conforti
A recent study by Eil at al. published in Nature in September 2016 provides evidence that alterations of the K(+) homeostasis of tumor infiltrating lymphocytes (TILs) in necrotic areas of the tumor microenvironment (TME) suppress the function of effector T cells. Furthermore, they establish that overexpression of K(+) channels in T lymphocytes counterbalances this negative effect of the TME and restores the ability of TILs to function, ultimately leading to increased survival of tumor bearing mice. Thus, K(+) channels in T lymphocytes become interesting new targets for novel immunotherapies in cancer...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28105230/dendritic-cell-activated-cytokine-induced-killer-cell-mediated-immunotherapy-is-safe-and-effective-for-cancer-patients-65-years-old
#8
Yanfeng Liu, Haibo Liu, Hausheng Liu, Pengcheng He, Jing Li, Xin Liu, Limei Chen, Mengchang Wang, Jiejing Xi, Huaiyu Wang, Haitao Zhang, Ying Zhu, Wei Zhu, Jing Ning, Caili Guo, Chunhong Sun, Mei Zhang
Individuals >65 years old account for a large proportion of cancer patients, and usually have poor prognoses due to relative weaker physiological function and lower drug tolerance. To characterize the efficacy and safety of dendritic cell (DC)-activated cytokine-induced killer cell (CIK)-mediated treatment, and develop an adoptive immunotherapy for cancer patients >65 years old, a retrospective study was performed in 58 cancer sufferers who received 1-4 cycles of DC-activated CIK (DC-CIK) treatment and evaluated the response (tumor remission rate) and toxicity (side effects to the treatment)...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28104840/tumor-aneuploidy-correlates-with-markers-of-immune-evasion-and-with-reduced-response-to-immunotherapy
#9
Teresa Davoli, Hajime Uno, Eric C Wooten, Stephen J Elledge
Immunotherapies based on immune checkpoint blockade are highly effective in a subset of patients. An ongoing challenge is the identification of biomarkers that predict which patients will benefit from these therapies. Aneuploidy, also known as somatic copy number alterations (SCNAs), is widespread in cancer and is posited to drive tumorigenesis. Analyzing 12 human cancer types, we find that, for most, highly aneuploid tumors show reduced expression of markers of cytotoxic infiltrating immune cells, especially CD8(+) T cells, and increased expression of cell proliferation markers...
January 20, 2017: Science
https://www.readbyqxmd.com/read/28104684/broad-and-conserved-immune-regulation-by-genetically-heterogeneous-melanoma-cells
#10
Natalie J Neubert, Laure Tillé, David Barras, Charlotte Soneson, Petra Baumgaertner, Donata Rimoldi, David Gfeller, Mauro Delorenzi, Silvia A Fuertes Marraco, Daniel E Speiser
While mutations drive cancer, it is less clear to what extent genetic defects control immune mechanisms and confer resistance to cytotoxic T lymphocyte (CTL)-based immunotherapy. Here we studied the reactions of malignant and benign melanocyte lines to CTL using flow cytometry and gene expression analyses. We found rapid and broad upregulation of immune regulatory genes, essentially triggered by CTL-derived IFNγ and augmented by TNFα. These reactions were predominantly homogenous, independent of oncogenic driver mutations and similar in benign and malignant cells...
January 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28103738/pharmacological-management-of-relapsed-refractory-nsclc-with-chemical-drugs
#11
Niki Karachaliou, Aaron E Sosa, Feliciano Barron Barron, Maria Gonzalez Cao, Mariacarmela Santarpia, Rafael Rosell
Lung cancer is the leading cause of cancer death in both genders. In the early stages the disease is asymptomatic and most patients appear with metastasis at the time of the diagnosis. The discovery of key oncogenic events mainly in lung adenocarcinoma, like EGFR mutations or ALK rearrangements has changed the treatment landscape and has improved the prognosis of lung cancer patients. Inevitably, all patients initially treated with either chemotherapy or targeted therapies develop resistance and require a second-line therapeutic approach...
January 20, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28103239/identifying-t-cell-receptors-from-high-throughput-sequencing-dealing-with-promiscuity-in-tcr%C3%AE-and-tcr%C3%AE-pairing
#12
Edward S Lee, Paul G Thomas, Jeff E Mold, Andrew J Yates
Characterisation of the T cell receptors (TCR) involved in immune responses is important for the design of vaccines and immunotherapies for cancer and autoimmune disease. The specificity of the interaction between the TCR heterodimer and its peptide-MHC ligand derives largely from the juxtaposed hypervariable CDR3 regions on the TCRα and TCRβ chains, and obtaining the paired sequences of these regions is a standard for functionally defining the TCR. A brute force approach to identifying the TCRs in a population of T cells is to use high-throughput single-cell sequencing, but currently this process remains costly and risks missing small clones...
January 19, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28102876/aging-tumour-cells-to-cure-cancer-pro-senescence-therapy-for-cancer
#13
Arianna Calcinotto, Andrea Alimonti
Robust scientific evidence demonstrates that senes-cence induction in cancer works as a potent weapon to eradicate tumorigenesis. Therapies that enhance senescence not only promote a stable cell growth arrest but also work as a strong stimulus for the acti-vation of the antitumour immune response. However, recent advances suggest that if senescent tumour cells are not cleared from the tumours, they may promote tumour progression and metastasis. In this article, we focus on concepts that are relevant to a pro-senescence therapeutic approach, including caveats, and we propose therapeutic strategies that involve the combined use of pro-senescence therapies with im-munotherapies to promote the clearance of senescent tumour cells...
January 19, 2017: Swiss Medical Weekly
https://www.readbyqxmd.com/read/28102259/elements-of-cancer-immunity-and-the-cancer-immune-set-point
#14
Daniel S Chen, Ira Mellman
Immunotherapy is proving to be an effective therapeutic approach in a variety of cancers. But despite the clinical success of antibodies against the immune regulators CTLA4 and PD-L1/PD-1, only a subset of people exhibit durable responses, suggesting that a broader view of cancer immunity is required. Immunity is influenced by a complex set of tumour, host and environmental factors that govern the strength and timing of the anticancer response. Clinical studies are beginning to define these factors as immune profiles that can predict responses to immunotherapy...
January 18, 2017: Nature
https://www.readbyqxmd.com/read/28102051/t-cell-immunoglobulin-mucin-3-blockade-drives-an-antitumor-immune-response-in-head-and-neck-cancer
#15
Jian-Feng Liu, Si-Rui Ma, Liang Mao, Lin-Lin Bu, Guang-Tao Yu, Yi-Cun Li, Cong-Fa Huang, Wei-Wei Deng, Ashok B Kulkarni, Wen-Feng Zhang, Zhi-Jun Sun
T-cell immunoglobulin mucin 3 (TIM3) contributes to immune suppression during progression of many cancers, but the precise role of TIM3 in head and neck squamous cell carcinoma (HNSCC) is not clearly understood. In this study, we report that TIM3 expression was significantly up-regulated in patients with HNSCC and associated with lymph node metastasis. Additionally, TIM3 expression was increased in patients with recurrent HNSCC and patients with preradiotherapy or prechemotherapy. We also characterized CD8(+) T cells and CD11b(+) CD33(+) myeloid-derived suppressor cells (MDSCs) in human HNSCC, and found that their expression was positively correlated with TIM3 expression...
December 15, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28101811/the-distribution-and-function-of-human-memory-t-cell-subsets-in-lung-cancer
#16
Si Yuan Sheng, Yong Gu, Chuan Gang Lu, Jian Yong Zou, Hai Hong, RongFu Wang
The distribution and function of T lymphocytes in human lung cancer remain limited. In this study, we investigated the properties of human T cell subsets in the blood of non-small cell lung cancer (NSCLC) patients. We found a relatively normal level of CD4+ subsets in the blood of NSCLC patients, but CD8+ effector T cells increased and CD8+ effector memory cells declined compared to the healthy donors. To further analyze their properties, we stimulated the peripheral blood mononuclear cells (PBMCs) of NSCLC patients by mitogens to examine cytokine production...
January 19, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28101230/effect-of-il-17-in-the-development-of-colon-cancer-in-mice
#17
Lijuan Yang, Hao Liu, Lili Zhang, Jie Hu, Haixia Chen, Lei Wang, Xiaolin Yin, Quanhai Li, Yixin Qi
Cytokine therapy is commonly used for tumor immunotherapy. Although early studies focused directly on the tumor, current investigations are more attentive of the tumor microenvironment. Various immune cells and related cytokines in the tumor microenvironment play an important role in the occurrence and development of tumor. Interleukin (IL)-17 is the characteristic cytokine produced by Th17 cells. IL-17 has been associated with various immune responses. The results of previous studies showed that IL-17 can significantly reduce the size of transplanted tumors in tumor-bearing mice, albeit it has no effect on the survival time of mice...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28101225/monocytic-myeloid-derived-suppressor-cells-as-a-potent-suppressor-of-tumor-immunity-in-non-small-cell-lung-cancer
#18
Katarzyna Pogoda, Maria Pyszniak, Paweł Rybojad, Jacek Tabarkiewicz
Immunotherapy is a promising therapeutic option for patients with non-small cell lung cancer (NSCLC) who do not qualify for surgery. In patients with advanced NSCLC, systemic immune suppression is frequently observed, therefore, researchers are investigating the tumor microenvironment for less invasive and more effective methods of treating lung cancer. Monocytic myeloid-derived suppressor cells (Mo-MDSCs) are potent suppressors of tumor immunity; therefore, this population may significantly impede the application of immunotherapy to treat cancer...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28101034/a-case-of-poorly-differentiated-large-cell-neuroendocrine-carcinoma-of-the-cecum-a-rare-malignancy-with-review-of-the-literature
#19
Andrew T Mertz, Michelle A Ojemuyiwa
Poorly differentiated neuroendocrine carcinomas (NECs) are rare tumors that can arise anywhere along the gastrointestinal tract. They often present in advanced stage and portend a poor prognosis when compared to adenocarcinomas of the same stage. Characterization of these tumors is best accomplished with tissue biopsy, as peripheral tumor markers commonly used in NECs are of little utility. Therapeutic strategies often involve chemotherapeutic regimens that have been used to treat small-cell lung cancer. Recent studies have shown that programmed death-ligand 1 (PD-L1) expression within poorly differentiated NECs is a poor prognostic indicator...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/28100832/reporter-gene-imaging-of-targeted-t-cell-immunotherapy-in-recurrent-glioma
#20
Khun Visith Keu, Timothy H Witney, Shahriar Yaghoubi, Jarrett Rosenberg, Anita Kurien, Rachel Magnusson, John Williams, Frezghi Habte, Jamie R Wagner, Stephen Forman, Christine Brown, Martin Allen-Auerbach, Johannes Czernin, Winson Tang, Michael C Jensen, Behnam Badie, Sanjiv S Gambhir
High-grade gliomas are aggressive cancers that often become rapidly fatal. Immunotherapy using CD8(+) cytotoxic T lymphocytes (CTLs), engineered to express both herpes simplex virus type 1 thymidine kinase (HSV1-TK) and interleukin-13 (IL-13) zetakine chimeric antigen receptor (CAR), is a treatment strategy with considerable potential. To optimize this and related immunotherapies, it would be helpful to monitor CTL viability and trafficking to glioma cells. We show that noninvasive positron emission tomography (PET) imaging with 9-[4-[(18)F]fluoro-3-(hydroxymethyl)butyl]guanine ([(18)F]FHBG) can track HSV1-tk reporter gene expression present in CAR-engineered CTLs...
January 18, 2017: Science Translational Medicine
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