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https://www.readbyqxmd.com/read/27920468/immune-checkpoint-therapy-for-pancreatic-cancer
#1
REVIEW
Henrik Johansson, Roland Andersson, Monika Bauden, Sarah Hammes, Stefan Holdenrieder, Daniel Ansari
Novel treatment modalities are necessary for pancreatic cancer. Immunotherapy with immune checkpoint inhibition has shown effect in other solid tumors, and could have a place in pancreatic cancer treatment. Most available clinical studies on immune checkpoint inhibitors for pancreatic cancer are not yet completed and are still recruiting patients. Among the completed trials, there have been findings of a preliminary nature such as delayed disease progression and enhanced overall survival after treatment with immune checkpoint inhibitors in mono- or combination therapy...
November 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27920218/a-molecular-basis-for-the-presentation-of-phosphorylated-peptides-by-hla-b-antigens
#2
Adán Alpízar, Fabio Marino, Antonio Ramos-Fernández, Manuel Lombardía, Anita Jeko, Florencio Pazos, Alberto Paradela, César Santiago, Albert J R Heck, Miguel Marcilla
As aberrant protein phosphorylation is a hallmark of tumor cells, the display of tumor-specific phosphopeptides by Human Leukocyte Antigen (HLA) class I molecules can be exploited in the treatment of cancer by T-cell-based immunotherapy. Yet, the characterization and prediction of HLA-I phospholigands is challenging as the molecular determinants of the presentation of such post-translationally modified peptides are not fully understood. Here, we employed a peptidomic workflow to identify 256 unique phosphorylated ligands associated with HLA-B*40, -B*27, -B*39 or -B*07...
December 5, 2016: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/27920023/il4-from-t-follicular-helper-cells-downregulates-antitumor-immunity
#3
Hidekazu Shirota, Dennis M Klinman, Shuku-Ei Ito, Hiroyasu Ito, Masato Kubo, Chikashi Ishioka
Immune cells constitute a large fraction of the tumor microenvironment and modulate tumor progression. Clinical data indicate that chronic inflammation is present at tumor sites and that IL4 in particular is upregulated. Here we demonstrate that T follicular helper (Tfh) cells arise in tumor-draining lymph nodes where they produce an abundance of IL4. Deletion of IL4-expressing Tfh cells improves antitumor immunity, delays tumor growth, and reduces the generation of immunosuppressive myeloid cells in the LNs...
December 5, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27917371/hijacker-of-the-antitumor-immune-response-autophagy-is-showing-its-worst-facet
#4
REVIEW
Elodie Viry, Muhammad Zaeem Noman, Tsolère Arakelian, Audrey Lequeux, Salem Chouaib, Guy Berchem, Etienne Moussay, Jérôme Paggetti, Bassam Janji
Macroautophagy (hereafter referred to as autophagy) is a housekeeping process constitutively executed at basal level in all cells to promote cellular homeostasis by regulating organelle and protein turnover. However, autophagy deregulation caused by several stress factors, such as hypoxia, is prevalent in many cancers. It is now well established that autophagy can act as tumor suppressor or tumor promoter depending on tumor type, stage, and genetic context. In developed tumors, autophagy promotes the survival of cancer cells and therefore operates as a cell resistance mechanism...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27916607/current-status-of-biomarker-and-targeted-nanoparticle-development-the-precision-oncology-approach-for-pancreatic-cancer-therapy
#5
Lei Zhu, Charles Staley, David Kooby, Bassel El-Rays, Hui Mao, Lily Yang
Pancreatic cancer remains one of the major causes of cancer-related mortality. The majority of pancreatic cancer patients are diagnosed at the advanced stage with unresectable and drug resistant tumors. The new treatments with the combination of chemotherapy, molecular targeted therapy, and immunotherapy have shown modest effects on therapeutic efficacy and survival of the patients. Therefore, there is an urgent need to develop effective therapeutic approaches targeting highly heterogeneous pancreatic cancer cells and tumor microenvironments...
December 1, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27916291/intratumoral-immunization-by-p19arf-and-interferon-%C3%AE-gene-transfer-in-a-heterotopic-mouse-model-of-lung-carcinoma
#6
João Paulo Portela Catani, Ruan F V Medrano, Aline Hunger, Paulo Del Valle, Sandy Adjemian, Daniela Bertolini Zanatta, Guido Kroemer, Eugenia Costanzi-Strauss, Bryan E Strauss
Therapeutic strategies that act by eliciting and enhancing antitumor immunity have been clinically validated as an effective treatment modality but may benefit from the induction of both cell death and immune activation as primary stimuli. Using our AdRGD-PG adenovector platform, we show here for the first time that in situ gene transfer of p19Arf and interferon-β (IFNβ) in the LLC1 mouse model of lung carcinoma acts as an immunotherapy. Although p19Arf is sufficient to induce cell death, only its pairing with IFNβ significantly induced markers of immunogenic cell death...
December 2016: Translational Oncology
https://www.readbyqxmd.com/read/27915972/resistance-to-cell-death-and-its-modulation-in-cancer-stem-cells
#7
Ahmad R Safa
Accumulating evidence has demonstrated that human cancers arise from various tissues of origin that initiate from cancer stem cells (CSCs) or cancer-initiating cells. The extrinsic and intrinsic apoptotic pathways are dysregulated in CSCs, and these cells play crucial roles in tumor initiation, progression, cell death resistance, chemo- and radiotherapy resistance, and tumor recurrence. Understanding CSC-specific signaling proteins and pathways is necessary to identify specific therapeutic targets that may lead to the development of more efficient therapies selectively targeting CSCs...
2016: Critical Reviews in Oncogenesis
https://www.readbyqxmd.com/read/27913998/immunotherapy-for-breast-cancer-past-present-and-future
#8
Alison Spellman, Shou-Ching Tang
Immunotherapy has shown promise in many solid tumors including melanoma and non-small cell lung cancer with an evolving role in breast cancer. Immunotherapy encompasses a wide range of therapies including immune checkpoint inhibition, monoclonal antibodies, bispecific antibodies, vaccinations, antibody-drug conjugates, and identifying other emerging interventions targeting the tumor microenvironment. Increasing efficacy of these treatments in breast cancer patients requires identification of better biomarkers to guide patient selection; recognizing when to initiate these therapies in multi-modality treatment plans; establishing novel assays to monitor immune-mediated responses; and creating combined systemic therapy options incorporating conventional treatments such as chemotherapy and endocrine therapy...
December 2, 2016: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/27913506/checkpoint-inhibition-and-cellular-immunotherapy-in-lymphoma
#9
Premal Lulla, Helen E Heslop
Hodgkin and non-Hodgkin lymphoma are both good targets for immunotherapy, as they are accessible to antibodies and cell-based immunotherapy, express costimulatory molecules, and express lineage-restricted, viral, and unique tumor antigens. Blockade of the programmed-death 1 (PD-1) immune checkpoint has produced very encouraging response rates in patients with Hodgkin lymphoma, whereas adoptive transfer of Epstein-Barr Virus (EBV)-specific T cells has shown clinical activity in patients with posttransplant lymphoma and other EBV-associated lymphomas...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27912893/-perioperative-therapies-in-surgical-non-n2%C3%A2-non-small-cell-lung-cancer
#10
REVIEW
Anne-Marie Ruppert, Armelle Lavolé, Jalal Assouad, Jacques Cadranel, Marie Wislez
Platinum-based perioperative chemotherapy is actually the standard of care in stage II-IIIa non-small cell lung cancer (NSCLC). A benefit may also be seen in stage IB NSCLC with tumors of more than 4cm of diameter. Perioperative chemotherapy improves 5-year survival of 4 to 15%. This benefit is mainly proved by postoperative chemotherapy trials. Nevertheless, preoperative chemotherapy has advantages: a better tolerance, an estimation of tumor chemosensibility, without an increased postoperative morbimortality...
November 29, 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/27912828/lung-cancer-biomarkers
#11
REVIEW
Pamela Villalobos, Ignacio I Wistuba
The molecular characterization of lung cancer has changed the classification and treatment of these tumors, becoming an essential component of pathologic diagnosis and oncologic therapy decisions. Through the recognition of novel biomarkers, such as epidermal growth factor receptor mutations and anaplastic lymphoma kinase translocations, it is possible to identify subsets of patients who benefit from targeted molecular therapies. The success of targeted anticancer therapies and new immunotherapy approaches has created a new paradigm of personalized therapy and has led to accelerated development of new drugs for lung cancer treatment...
February 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/27912060/the-hippo-pathway-kinases-lats1-2-suppress-cancer-immunity
#12
Toshiro Moroishi, Tomoko Hayashi, Wei-Wei Pan, Yu Fujita, Matthew V Holt, Jun Qin, Dennis A Carson, Kun-Liang Guan
Poorly immunogenic tumor cells evade host immunity and grow even in the presence of an intact immune system, but the complex mechanisms regulating tumor immunogenicity have not been elucidated. Here, we discovered an unexpected role of the Hippo pathway in suppressing anti-tumor immunity. We demonstrate that, in three different murine syngeneic tumor models (B16, SCC7, and 4T1), loss of the Hippo pathway kinases LATS1/2 (large tumor suppressor 1 and 2) in tumor cells inhibits tumor growth. Tumor regression by LATS1/2 deletion requires adaptive immune responses, and LATS1/2 deficiency enhances tumor vaccine efficacy...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27911793/heterogeneous-yet-stable-v%C3%AE-2-t-cell-profiles-define-distinct-cytotoxic-effector-potentials-in-healthy-human-individuals
#13
Paul L Ryan, Nital Sumaria, Christopher J Holland, Claire M Bradford, Natalia Izotova, Capucine L Grandjean, Ali S Jawad, Lesley A Bergmeier, Daniel J Pennington
Human γδ T cells display potent responses to pathogens and malignancies. Of particular interest are those expressing a γδ T-cell receptor (TCR) incorporating TCRδ-chain variable-region-2 [Vδ2((+))], which are activated by pathogen-derived phosphoantigens (pAgs), or host-derived pAgs that accumulate in transformed cells or in cells exposed to aminobisphosphonates. Once activated, Vδ2((+)) T cells exhibit multiple effector functions that have made them attractive candidates for immunotherapy. Despite this, clinical trials have reported mixed patient responses, highlighting a need for better understanding of Vδ2((+)) T-cell biology...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911726/dichotomous-roles-of-tgf-%C3%AE-in-human-cancer
#14
REVIEW
Jennifer J Huang, Gerard C Blobe
Transforming growth factor-β (TGF-β) mediates numerous biological processes, including embryonic development and the maintenance of cellular homeostasis in a context-dependent manner. Consistent with its central role in maintaining cellular homeostasis, inhibition of TGF-β signaling results in disruption of normal homeostatic processes and subsequent carcinogenesis, defining the TGF-β signaling pathway as a tumor suppressor. However, once carcinogenesis is initiated, the TGF-β signaling pathway promotes cancer progression...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27911363/generation-of-induced-pluripotent-stem-cells-from-human-melanoma-tumor-infiltrating-lymphocytes
#15
Hidehito Saito, Kumiko Iwabuchi, Noemi Fusaki, Fumito Ito
Adoptive transfer of ex vivo expanded autologous tumor-infiltrating lymphocytes (TILs) can mediate durable and complete responses in significant subsets of patients with metastatic melanoma. Major obstacles of this approach are the reduced viability of transferred T cells, caused by telomere shortening, and the limited number of TILs obtained from patients. Less-differentiated T cells with long telomeres would be an ideal T cell subset for adoptive T cell therapy;however, generating large numbers of these less-differentiated T cells is problematic...
November 11, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27911273/robust-detection-of-immune-transcripts-in-ffpe-samples-using-targeted-rna-sequencing
#16
Benjamin E Paluch, Sean T Glenn, Jeffrey M Conroy, Antonios Papanicolau-Sengos, Wiam Bshara, Angela R Omilian, Elizabeth Brese, Mary Nesline, Blake Burgher, Jonathan Andreas, Kunle Odunsi, Kevin Eng, Ji He, Maochun Qin, Mark Gardner, Lorenzo Galluzzi, Carl D Morrison
Current criteria for identifying cancer patients suitable for immunotherapy with immune checkpoint blockers (ICBs) are subjective and prone to misinterpretation, as they mainly rely on the visual assessment of CD274 (best known as PD-L1) expression levels by immunohistochemistry (IHC). To address this issue, we developed a RNA sequencing (RNAseq)-based approach that specifically measures the abundance of immune transcripts in formalin-fixed paraffin embedded (FFPE) specimens. Besides exhibiting superior sensitivity as compared to whole transcriptome RNAseq, our assay requires little starting material, implying that it is compatible with RNA degradation normally caused by formalin...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27910927/novel-chemoimmunotherapeutic-strategy-for-hepatocellular-carcinoma-based-on-a-genome-wide-association-study
#17
Kaku Goto, Dorcas A Annan, Tomoko Morita, Wenwen Li, Ryosuke Muroyama, Yasuo Matsubara, Sayaka Ito, Ryo Nakagawa, Yasushi Tanoue, Masahisa Jinushi, Naoya Kato
Pharmacotherapeutic options are limited for hepatocellular carcinoma (HCC). Recently, we identified the anti-tumor ligand MHC class I polypeptide-related sequence A (MICA) gene as a susceptibility gene for hepatitis C virus-induced HCC in a genome-wide association study (GWAS). To prove the concept of HCC immunotherapy based on the results of a GWAS, in the present study, we searched for drugs that could restore MICA expression. A screen of the FDA-approved drug library identified the anti-cancer agent vorinostat as the strongest hit, suggesting histone deacetylase inhibitors (HDACis) as potent candidates...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910914/in-vivo-stepwise-immunomodulation-using-chitosan-nanoparticles-as-a-platform-nanotechnology-for-cancer-immunotherapy
#18
Hee Dong Han, Yeongseon Byeon, Jong-Hwa Jang, Hat Nim Jeon, Ga Hee Kim, Min Gi Kim, Chan-Gi Pack, Tae Heung Kang, In Duk Jung, Yong Taik Lim, Young Joo Lee, Jeong-Won Lee, Byung Cheol Shin, Hyung Jun Ahn, Anil K Sood, Yeong-Min Park
Dentritic cell (DC)-based cancer immunotherapy faces challenges in both efficacy and practicality. However, DC-based vaccination requires multiple injections and elaborates ex vivo manipulation, which substantially limits their use. Therefore, we sought to develop a chitosan nanoparticle (CH-NP)-based platform for the next generation of vaccines to bypass the ex vivo manipulation and induce immune responses via active delivery of polyinosinic-polycytidylic acid sodium salt (poly I:C) to target Toll-like receptor 3 (TLR3) in endosomes...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910859/t-cell-programming-in-pancreatic-adenocarcinoma-a-review
#19
REVIEW
Y D Seo, V G Pillarisetty
Despite recent advancements in multimodal therapy, pancreatic ductal adenocarcinoma (PDA) continues to have a dismal prognosis. In the era of burgeoning immune therapies against previously difficult-to-treat malignancies, there has been growing interest in activating the immune system against PDA; however, unlike in other cancers such as melanoma and lymphoma, immunotherapy has not yielded many clinically significant results. To harness these mechanisms for therapeutic use, an in-depth understanding of T-cell programming in the immune microenvironment of PDA must be achieved...
December 2, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27910858/immunosuppression-in-liver-tumors-opening-the-portal-to-effective-immunotherapy
#20
REVIEW
P Guha, J Reha, S C Katz
We have recently witnessed substantial progress with immunotherapy for selected diseases. Checkpoint inhibitors and chimeric antigen receptor T (CAR-T) cells are among the most promising agents. Whereas much of the early success with CAR-T cells has been demonstrated with hematological malignancies, important barriers remain for the application of CAR-T cell therapies for the management of metastatic solid tumors. The challenges are particularly apparent when considering primary and metastatic tumors in the liver...
December 2, 2016: Cancer Gene Therapy
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