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Immunotherapy lung cancer

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https://www.readbyqxmd.com/read/28103738/pharmacological-management-of-relapsed-refractory-nsclc-with-chemical-drugs
#1
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/28101811/the-distribution-and-function-of-human-memory-t-cell-subsets-in-lung-cancer
#2
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/28101225/monocytic-myeloid-derived-suppressor-cells-as-a-potent-suppressor-of-tumor-immunity-in-non-small-cell-lung-cancer
#3
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
#4
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/28096300/enhanced-suppression-of-polyclonal-cd8-25-regulatory-t-cells-via-exosomal-arming-of-antigen-specific-peptide-mhc-complexes
#5
Chuanyong Mu, Xueshu Zhang, Lu Wang, Aizhang Xu, Khawaja Ashfaque Ahmed, Xueqin Pang, Rajni Chibbar, Andrew Freywald, Jianan Huang, Yehan Zhu, Jim Xiang
Compared with CD4(+)25(+) regulatory T cells (Tregs), the mechanisms for natural, polyclonal CD8(+)25(+) Treg immune suppression have been significantly less studied. We previously showed that polyclonal T cells can acquire antigen-specific targeting activity through arming with exosomal peptide-MHC (pMHC). In this study, we assessed the suppressive effect of CD8(+)25(+) Tregs or CD8(+)25(+) Tregs armed with ovalbumin (OVA)-specific exosomes on other immune cells and OVA-specific dendritic cell (DCOVA)-stimulated antitumor immunity...
January 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28092804/enhancement-of-nk-cell-mediated-lysis-of-non-small-lung-cancer-cells-by-npkc-activator-ingenol-3-20-dibenzoate
#6
Chenyuan Gong, Chao Yao, Zihang Xu, Zhongya Ni, Xiaowen Zhu, Lixin Wang, Xuewei Yan, Wuxiong Zhou, Shiguo Zhu
The IFN-γ production is crucial for NK cell-mediated lysis of cancer cells. Thus increasing the IFN-γ production by NK cells may be an ideal strategy to improve their tumoricidal effect. Since the focus on new drug development has shifted towards natural products, limited information is out there about natural products that enhance the IFN-γ production by NK cells. In this study, through a high-throughput screening, we have identified a natural product ingenol 3,20 dibenzoate (IDB), an activator of tumor suppressor protein kinase C (PKC) isozymes, could increase the IFN-γ production and degranulation by NK cells, especially when NK cells were stimulated by non-small lung cancer (NSCLC) cells...
January 13, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28089762/long-terms-results-of-a-trial-of-concurrent-chemotherapy-and-escalating-doses-of-radiation-for-unresectable-non-small-cell-lung-cancer-ncctg-n0028-alliance
#7
Steven E Schild, Shauna L Hillman, Angelina D Tan, Helen J Ross, William L McGinnis, Yolanda A Garces, David L Graham, Alex A Adjei, James R Jett
INTRODUCTION OR HYPOTHESIS: This phase I/II trial was originally designed to determine the maximally tolerated dose(MTD) of thoracic radiotherapy(TRT) as part of a combined modality approach. This report includes the long-term outcome of patients treated on this study. The phase II portion was never completed as RTOG-0617 opened before it was concluded. METHODS: The MTD was defined as 74Gy in 37 fractions in this study. Twenty-five patients with unresectable non-small cell lung cancer(NSCLC) were treated with 2Gy daily fractions and concurrent weekly carboplatin and paclitaxel...
January 12, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28088513/an-immunogram-for-the-cancer-immunity-cycle-towards-personalized-immunotherapy-of-lung-cancer
#8
Takahiro Karasaki, Kazuhiro Nagayama, Hideki Kuwano, Jun-Ichi Nitadori, Masaaki Sato, Masaki Anraku, Akihiro Hosoi, Hirokazu Matsushita, Yasuyuki Morishita, Kosuke Kashiwabara, Masaki Takazawa, Osamu Ohara, Kazuhiro Kakimi, Jun Nakajima
INTRODUCTION: The interaction of immune cells and cancer cells shapes the immunosuppressive tumor microenvironment. For successful cancer immunotherapy, comprehensive knowledge of anti-tumor immunity as a dynamic spacio-temporal process is required for each individual patient. To this end, we developed an immunogram for the cancer-immunity cycle using next-generation sequencing. METHODS: Whole-exome sequencing and RNA-Seq was performed in 20 non-small cell lung cancer patients (12 adenocarcinoma, 7 squamous cell carcinoma, and 1 large cell neuroendocrine carcinoma)...
January 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28074864/a-novel-monoclonal-antibody-targeting-coxsackie-virus-and-adenovirus-receptor-inhibits-tumor-growth-in-vivo
#9
Manabu Kawada, Hiroyuki Inoue, Masunori Kajikawa, Masahito Sugiura, Shuichi Sakamoto, Sakiko Urano, Chigusa Karasawa, Ihomi Usami, Mitsuru Futakuchi, Tohru Masuda
To create a new anti-tumor antibody, we conducted signal sequence trap by retrovirus-meditated expression method and identified coxsackie virus and adenovirus receptor (CXADR) as an appropriate target. We developed monoclonal antibodies against human CXADR and found that one antibody (6G10A) significantly inhibited the growth of subcutaneous as well as orthotopic xenografts of human prostate cancer cells in vivo. Furthermore, 6G10A also inhibited other cancer xenografts expressing CXADR, such as pancreatic and colorectal cancer cells...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28073845/agreement-between-programmed-cell-death-ligand-1-diagnostic-assays-across-multiple-protein-expression-cut-offs-in-non-small-cell-lung-cancer
#10
Marianne J Ratcliffe, Alan Sharpe, Anita Midha, Craig Barker, Marietta Scott, Paul Scorer, Hytham Al-Masri, Marlon Rebelatto, Jill Walker
PURPOSE: agents:Immunotherapies targeting programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) demonstrate encouraging antitumor activity and manageable tolerability in non-small cell lung cancer (NSCLC), especially in patients with high tumor PD-L1 expression, as detected by companion or complementary diagnostic assays developed for individual agents. A laboratory is unlikely to use multiple assay platforms. Furthermore, commercially available diagnostic assays are not standardized and different assay methods could lead to inappropriate treatment selection...
January 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28067949/fda-approves-breakthrough-immunotherapy-for-patients-with-non-small-cell-lung-cancer
#11
Carrie Printz
No abstract text is available yet for this article.
January 1, 2017: Cancer
https://www.readbyqxmd.com/read/28064556/pd-1-checkpoint-blockade-alone-or-combined-pd-1-and-ctla-4-blockade-as-immunotherapy-for-lung-cancer
#12
Tawee Tanvetyanon, Jhanelle E Gray, Scott J Antonia
Signaling through T-cell surface, an immune checkpoint protein such as PD-1 or CTLA-4 helps dampen or terminate unwanted immune responses. Blocking a single immune checkpoint or multiple checkpoints simultaneously can generate anti-tumor activity against a variety of cancers including lung cancer. Area covered: This review highlights the results of recent clinical studies of single or combination checkpoint inhibitor immunotherapy in non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC). The authors discuss pembrolizumab and pembrolizumab plus ipilimumab, durvalumab and durvalumab plus tremelimumab, nivolumab and nivolumab plus ipilimumab for NSCLC as well as nivolumab and nivolumab plus ipilimumab for SCLC...
January 18, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28063623/immune-checkpoint-inhibitors-in-lung-cancer-an-unheralded-opportunity
#13
R Marshall, A Popple, T Kordbacheh, J Honeychurch, C Faivre-Finn, T Illidge
Lung cancer remains the leading cause of cancer-related death worldwide, with non-small cell lung cancer accounting for 85% of the disease. Over 70% of patients present with locally advanced, non-resectable or metastatic disease and despite improvements in chemoradiotherapy regimens and the development of molecularly targeted agents, 5 year survival rates remain poor, with acquired resistance to novel targeted therapies becoming a growing concern. Currently there remains an unmet need in effectively treating and inducing durable responses in advanced disease...
January 4, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/28062694/effective-combination-of-innate-and-adaptive-immunotherapeutic-approaches-in-a-mouse-melanoma-model
#14
Alexander L Rakhmilevich, Mildred Felder, Lauren Lever, Jacob Slowinski, Kayla Rasmussen, Anna Hoefges, Tyler J Van De Voort, Hans Loibner, Alan J Korman, Stephen D Gillies, Paul M Sondel
Most cancer immunotherapies include activation of either innate or adaptive immune responses. We hypothesized that the combined activation of both innate and adaptive immunity will result in better antitumor efficacy. We have previously shown the synergy of an agonistic anti-CD40 mAb (anti-CD40) and CpG-oligodeoxynucleotides in activating macrophages to induce tumor cell killing in mice. Separately, we have shown that a direct intratumoral injection of immunocytokine (IC), an anti-GD2 Ab linked to IL-2, can activate T and NK cells resulting in antitumor effects...
January 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28059852/immune-checkpoint-inhibitors-in-first-line-therapy-of-advanced-non-small-cell-lung-cancer
#15
Jordi Remon, Benjamin Besse
PURPOSE OF REVIEW: Evading immune destruction is a hallmark of cancer. The first therapeutic wave in immunotherapies comprised a series of monoclonal antibodies directed against the immune checkpoint molecules cytotoxic T-lymphocyte-associated protein 4, programmed death 1 (PD-1), and programmed death ligand-1 (PD-L1) revolutionizing the therapeutic landscape of advanced non-small cell lung cancer. They were validated initially as second-line treatment, becoming the new standard of care...
January 3, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28057179/biomarqueurs-pr%C3%A3-dictifs-de-r%C3%A3-ponse-aux-traitements-bloquant-les-voies-de-costimulation-inhibitrices
#16
Franck Pagès, Clémence Granier, Amos Kirilovsky, Carine Elsissy, Eric Tartour
Immunotherapies targeting co-inhibitory receptors recently open a new promising approach of cancer treatment. Indeed, an objective clinical response was observed after treatment by anti-CTLA-4 and anti-PD-1 in many indications but the treatment still failed in 70 to 80 % of cases treated. Given the adverse effects and the high cost of these therapies, there is a need for the development of biomarkers. This review focus on potential predictive biomarkers. In peripheral blood, high level of Il-2 soluble receptor at baseline and absence of ICOS+ CD4-T lymphocytes induction may be associated with the absence of clinical response for melanoma patients treated by ipilimumab (anti-CTLA-4)...
November 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/28055269/targeting-pd-1-pathway-a-new-hope-for-gastrointestinal-cancers
#17
Burak Bilgin, Mehmet An Sendur, Muhammed Bülent Akıncı, Didem Şener Dede, Bülent Yalçın
BACKGROUND: VEGF, HER2 and EGFR targeted agents are currently used in gastric, esophageal and colorectal cancers. However, treatment outcomes are still poor in most of the Gastrointestinal (GI) cancers. Immune checkpoints are one of the most promising immunotherapy approaches. In this review article, we aimed to discuss the efficacy and safety of anti-PD-1/PD-L1 therapies in GI cancers, including gastric, esophageal and colorectal cancer in the era of published or reported recent studies...
January 5, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28052005/bortezomib-augments-lymphocyte-stimulatory-cytokine-signaling-in-the-tumor-microenvironment-to-sustain-cd8-t-cell-antitumor-function
#18
Samuel T Pellom, Duafalia F Dudimah, Menaka C Thounaojam, Roman V Uzhachenko, Ashutosh Singhal, Ann Richmond, Anil Shanker
Tumor-induced immune tolerance poses a major challenge for therapeutic interventions aimed to manage cancer. We explored approaches to overcome T-cell suppression in murine breast and kidney adenocarcinomas, and lung fibrosarcoma expressing immunogenic antigens. We observed that treatment with a reversible proteasome inhibitor bortezomib (1 mg/kg body weight) in tumor-bearing mice significantly enhanced the expression of lymphocyte-stimulatory cytokines IL-2, IL-12, and IL-15. Notably, bortezomib administration reduced pulmonary nodules of mammary adenocarcinoma 4T1...
December 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/28049169/management-of-stage-i-and-ii-nonsmall-cell-lung-cancer
#19
Fiona McDonald, Michèle De Waele, Lizza E L Hendriks, Corinne Faivre-Finn, Anne-Marie C Dingemans, Paul E Van Schil
The incidence of stage I and II nonsmall cell lung cancer is likely to increase with the ageing population and introduction of screening for high-risk individuals. Optimal management requires multidisciplinary collaboration. Local treatments include surgery and radiotherapy and these are currently combined with (neo)adjuvant chemotherapy in specific cases to improve long-term outcome. Targeted therapies and immunotherapy may also become important therapeutic modalities in this patient group. For resectable disease in patients with low cardiopulmonary risk, complete surgical resection with lobectomy remains the gold standard...
January 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28039262/potential-predictive-value-of-tp53-and-kras-mutation-status-for-response-to-pd-1-blockade-immunotherapy-in-lung-adenocarcinoma
#20
Zhong-Yi Dong, Wenzhao Zhong, Xu-Chao Zhang, Jian Su, Zhi Xie, Si-Yang Liu, Hai-Yan Tu, Hua-Jun Chen, Yue-Li Sun, Qing Zhou, Jinji Yang, Xuening Yang, Jia-Xin Lin, Honghong Yan, Hao-Ran Zhai, Li-Xu Yan, Ri-Qiang Liao, Si-Pei Wu, Yi-Long Wu
PURPOSE: Although clinical studies have shown promise for targeting programmed cell death protein-1 (PD-1) and ligand (PD-L1) signaling in non-small cell lung cancer (NSCLC), the factors that predict which subtype patients will be responsive to checkpoint blockade are not fully understood. EXPERIMENTAL DESIGN: We performed an integrated analysis on the multiple-dimensional data types including genomic, transcriptomic, proteomic and clinical data from cohorts of lung adenocarcinoma public (Discovery Set) and internal (Validation Set) database and immunotherapeutic patients...
December 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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