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Cancer immunity cycle

Taiki Hakozaki, Yusuke Okuma, Jumpei Kashima
BACKGROUND: Currently, immune checkpoint (ICP) inhibitors are essential drugs for the treatment of non-small cell lung cancer (NSCLC). However, in patients previously treated with ICP inhibitors, the efficacy and safety of re-challenging the same or another ICP inhibitor remain unclear. CASE PRESENTATION: We present the case of a patient treated with nivolumab for advanced NSCLC who was previously treated with an ICP inhibitor as the first-line chemotherapy along with heavy cytotoxic chemotherapy...
March 20, 2018: BMC Cancer
M E Rodríguez-Ruiz, J L Perez-Gracia, I Rodríguez, C Alfaro, C Oñate, G Pérez, I Gil-Bazo, A Benito, S Inogés, A López-Diaz de Cerio, M Ponz-Sarvise, L Resano, P Berraondo, B Barbés, S Martin-Algarra, A Gúrpide, M F Sanmamed, C de Andrea, A M Salazar, I Melero
BACKGROUND: Combination immunotherapy has the potential to achieve additive or synergistic effects. Combined local injections of dsRNA analogues (mimicking viral RNA) and repeated vaccinations with tumor-lysate loaded dendritic cells shows efficacy against colon cancer mouse models. In the context of immunotherapy, radiotherapy can exert beneficial abscopal effects. PATIENTS AND METHODS: In this two-cohort pilot phase I study, 15 advanced cancer patients received two 4-week cycles of four intradermal daily doses of monocyte-derived dendritic cells preloaded with autologous tumor lysate and matured for 24h with poly-ICLC (Hiltonol), TNF-α and IFN-α...
March 14, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Jessica Da Gama Duarte, Sagun Parakh, Miles C Andrews, Katherine Woods, Anupama Pasam, Candani Tutuka, Simone Ostrouska, Jonathan M Blackburn, Andreas Behren, Jonathan Cebon
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced melanoma. The first ICI to demonstrate clinical benefit, ipilimumab, targets cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4); however, the long-term overall survival is just 22%. More than 40 years ago intralesional (IL) bacillus Calmette-Guérin (BCG), a living attenuated strain of Mycobacterium bovis , was found to induce tumor regression by stimulating cell-mediated immunity following a localized and self-limiting infection...
2018: Frontiers in Immunology
Neil H Segal, Aiwu R He, Toshihiko Doi, Ronald Levy, Shailender Bhatia, Michael J Pishvaian, Rossano Cesari, Ying Chen, Craig B Davis, Bo Huang, Aron D Thall, Ajay K Gopal
Purpose: Utomilumab (PF-05082566) is an agonistic mAb that engages the immune costimulatory molecule 4-1BB/CD137. In this first-in-human, phase I, open-label, multicenter, multiple-dose study (NCT01307267) we evaluated safety, tolerability, pharmacokinetics, preliminary clinical activity, and pharmacodynamics of single-agent utomilumab in patients with advanced malignancies. Experimental Design: Dose escalation was based on a standard 3+3 design for doses of utomilumab from 0.006 to 0.3 mg/kg every 4 weeks and a time-to-event continual reassessment method for utomilumab 0...
March 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
A Boussommier-Calleja, Y Atiyas, K Haase, M Headley, C Lewis, R D Kamm
Metastasis is the leading cause of cancer-related deaths. Recent developments in cancer immunotherapy have shown exciting therapeutic promise for metastatic patients. While most therapies target T cells, other immune cells, such as monocytes, hold great promise for therapeutic intervention. In our study, we provide primary evidence of direct engagement between human monocytes and tumor cells in a 3D vascularized microfluidic model. We first characterize the novel application of our model to investigate and visualize at high resolution the evolution of monocytes as they migrate from the intravascular to the extravascular micro-environment...
March 5, 2018: Biomaterials
David A Schaer, Richard P Beckmann, Jack A Dempsey, Lysiane Huber, Amelie Forest, Nelusha Amaladas, Yanxia Li, Ying Cindy Wang, Erik R Rasmussen, Darin Chin, Andrew Capen, Carmine Carpenito, Kirk A Staschke, Linda A Chung, Lacey M Litchfield, Farhana F Merzoug, Xueqian Gong, Philip W Iversen, Sean Buchanan, Alfonso de Dios, Ruslan D Novosiadly, Michael Kalos
Abemaciclib, an inhibitor of cyclin dependent kinases 4 and 6 (CDK4/6), has recently been approved for the treatment of hormone receptor-positive breast cancer. In this study, we use murine syngeneic tumor models and in vitro assays to investigate the impact of abemaciclib on T cells, the tumor immune microenvironment and the ability to combine with anti-PD-L1 blockade. Abemaciclib monotherapy resulted in tumor growth delay that was associated with an increased T cell inflammatory signature in tumors. Combination with anti-PD-L1 therapy led to complete tumor regressions and immunological memory, accompanied by enhanced antigen presentation, a T cell inflamed phenotype, and enhanced cell cycle control...
March 13, 2018: Cell Reports
Donata Szymczak, Jarosław Dybko, Kazimierz Kuliczkowski
Hypoxia, understood as low partial oxygen pressure, has become one of the most explored fields in recent years. Cellular response to hypoxia is mediated by hypoxia-inducible factors (HIFs) - potent transcription regulators, and their downstream pathways. In general, HIFs modify energy metabolism, inflammation and immune response, enhance cancer invasion, metastasis, resistance to treatment, and relapse. The influence of HIFs on the progression of leukemia is still under investigation in various studies, but in mice and some human models HIFs have been recognized as leukemia immortalizers by promoting leukemic stem cell quiescence and inhibiting their cell cycle...
February 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Sai Ge, Xia Xia, Chen Ding, Bei Zhen, Quan Zhou, Jinwen Feng, Jiajia Yuan, Rui Chen, Yumei Li, Zhongqi Ge, Jiafu Ji, Lianhai Zhang, Jiayuan Wang, Zhongwu Li, Yumei Lai, Ying Hu, Yanyan Li, Yilin Li, Jing Gao, Lin Chen, Jianming Xu, Chunchao Zhang, Sung Yun Jung, Jong Min Choi, Antrix Jain, Mingwei Liu, Lei Song, Wanlin Liu, Gaigai Guo, Tongqing Gong, Yin Huang, Yang Qiu, Wenwen Huang, Tieliu Shi, Weimin Zhu, Yi Wang, Fuchu He, Lin Shen, Jun Qin
The diffuse-type gastric cancer (DGC) is a subtype of gastric cancer with the worst prognosis and few treatment options. Here we present a dataset from 84 DGC patients, composed of a proteome of 11,340 gene products and mutation information of 274 cancer driver genes covering paired tumor and nearby tissue. DGC can be classified into three subtypes (PX1-3) based on the altered proteome alone. PX1 and PX2 exhibit dysregulation in the cell cycle and PX2 features an additional EMT process; PX3 is enriched in immune response proteins, has the worst survival, and is insensitive to chemotherapy...
March 8, 2018: Nature Communications
Leila Farahmand, Rezvan Esmaeili, Leila Eini, Keivan Majidzadeh-A
Purpose: Bone marrow-derived mesenchymal stem cells (MSCs) have the potential ability to differentiate into bone, muscle, fat, and cartilage lineage cells. Furthermore, MSCs are known to migrate into tumor-associated stroma of cancer. This tumor microenvironment consists of a dynamic network of growth factors, immune cells, fibroblasts, extracellular matrix, and MSCs. MSCs as nonhematopoietic stem cells affect tumor, epithelial cells by alteration proliferative capacity, morphology, and aggregation pattern of tumor cells...
January 2018: Journal of Cancer Research and Therapeutics
Yi Gao, Jianjian Yang, Yixin Cai, Shengling Fu, Ni Zhang, Xiangning Fu, Lequn Li
IFN-γ plays a crucial role in anti-tumor responses but also induces expression of PD-L1, a well-established inhibitor of anti-tumor immune function. Understanding how molecular signaling regulates the function of IFN-γ might improve its anti-tumor efficacy. Here we show that the tumor expression of IFN-γ expression alone has no significant prognostic value in patients with locally advanced lung adenocarcinoma. Surprisingly, patients with tumors expressing both IFN-γ and PD-L1 have the best prognosis compared to those with tumors expressing IFN-γ or PD-L1 alone...
March 8, 2018: International Journal of Cancer. Journal International du Cancer
Ghina Fakhri, Reem Akel, Ziad Salem, Ayman Tawil, Arafat Tfayli
Background: Pembrolizumab is a humanized monoclonal antibody which serves to enhance the antitumor immune response by targeting programmed cell death 1 receptor. The use of pembrolizumab plus carboplatin/pemetrexed combination therapy results in improvement in overall survival and progression-free survival rates for non-small cell lung cancer (NSCLC) patients as compared to chemotherapy alone. However, numerous immune-mediated toxicities of pembrolizumab have been reported. Case Presentation: We report the case of a 74-year-old male patient diagnosed with stage IIIA programmed death-ligand 1-positive non-small cell lung adenocarcinoma treated with 4 cycles of carboplatin/pemetrexed plus pembrolizumab combination therapy followed by 2 cycles of pembrolizumab treatment...
September 2017: Case Reports in Oncology
Haixia Shan, Pingfu Hou, Meng Zhang, Liantao Li, Yu Pan, Fang Chen, Tao Jiang, Jin Bai, Junnian Zheng
Polypyrimidine tract-binding protein 1 (PTBP1), a heterogeneous nuclear ribonucleoprotein, is a multi-functional RNA-binding protein. PTBP1 participates in a number of biological processes, including maintaining cell structure and motility, immunity, protein metabolism and the cell cycle. The present study aimed to investigate the association between PTBP1 expression and the prognosis and clinicopathological characteristics of patients with renal cell cancer (RCC). The potential mechanism of action of PTBP1 in the metastasis of RCC was also investigated...
March 2, 2018: International Journal of Oncology
Britta Weigelt, Rui Bi, Rahul Kumar, Pedro Blecua, Diana L Mandelker, Felipe C Geyer, Fresia Pareja, Paul A James, Fergus J Couch, Diana M Eccles, Fiona Blows, Paul Pharoah, Anqi Li, Pier Selenica, Raymond S Lim, Gowtham Jayakumaran, Nic Waddell, Ronglai Shen, Larry Norton, Hannah Y Wen, Simon N Powell, Nadeem Riaz, Mark E Robson, Jorge S Reis-Filho, Georgia Chenevix-Trench
Pathogenic germline variants in ataxia-telangiectasia mutated (ATM), a gene that plays a role in DNA damage response and cell cycle checkpoints, confer an increased breast cancer (BC) risk. Here, we investigated the phenotypic characteristics and landscape of somatic genetic alterations in 24 BCs from ATM germline mutation carriers by whole-exome and targeted sequencing. ATM-associated BCs were consistently hormone receptor positive and largely displayed minimal immune infiltrate. Although 79.2% of these tumors exhibited loss of heterozygosity of the ATM wild-type allele, none displayed high activity of mutational signature 3 associated with defective homologous recombination DNA (HRD) repair...
February 28, 2018: Journal of the National Cancer Institute
Chiaho Shih, Ching-Chun Yang, Gansukh Choijilsuren, Chih-Hsu Chang, An-Ting Liou
This infographic about hepatitis B virus explores its replication cycle, natural history of infection and pathogenesis, and how this can be controlled and treated. Hepatitis B virus (HBV) is a common worldwide blood-borne pathogen. Chronic hepatitis B can progress to an inactive carrier state, and then, in some patients, give rise to cirrhosis and cancer of the liver, leading to death. An HBV surface-antigen vaccine is effective, but treatments are currently not curative. HBV replicates via reverse transcription...
February 27, 2018: Trends in Microbiology
Xiaoxuan Xu, Shuang-Zheng Jia, Yi Dai, Jun-Ji Zhang, Xiaoyan Li, Jinghua Shi, Jinhua Leng, Jinghe Lang
Circular RNAs (circRNAs) are involved in the pathogenesis of many diseases, although their expression pattern and role in endometriosis remains unknown. Therefore, here, we profiled the expression patterns of circRNAs in ovarian ectopic and paired eutopic endometria as well as constructed a circRNA-miRNA-mRNA network. Circular RNA and messenger RNA (mRNA) expression profiles were assessed by a microarray analysis in 4 patients. Quantitative real-time polymerase chain reaction (qRT-PCR) validation of 8 circRNAs and mRNAs was conducted in another 37 patients...
January 1, 2018: Reproductive Sciences
Yuri Kosinsky, Simon J Dovedi, Kirill Peskov, Veronika Voronova, Lulu Chu, Helen Tomkinson, Nidal Al-Huniti, Donald R Stanski, Gabriel Helmlinger
BACKGROUND: Numerous oncology combination therapies involving modulators of the cancer immune cycle are being developed, yet quantitative simulation models predictive of outcome are lacking. We here present a model-based analysis of tumor size dynamics and immune markers, which integrates experimental data from multiple studies and provides a validated simulation framework predictive of biomarkers and anti-tumor response rates, for untested dosing sequences and schedules of combined radiation (RT) and anti PD-(L)1 therapies...
February 27, 2018: Journal for Immunotherapy of Cancer
Walburga Engel-Riedel, Jamie Lowe, Paulette Mattson, J Richard Trout, Richard D Huhn, Michele Gargano, Myra L Patchen, Richard Walsh, My My Trinh, Mariève Dupuis, Folker Schneller
BACKGROUND: BTH1677, a beta-glucan pathogen-associated molecular pattern molecule, drives an anti-cancer immune response in combination with oncology antibody therapies. This phase II study explored the efficacy, pharmacokinetics (PK), and safety of BTH1677 combined with bevacizumab/carboplatin/paclitaxel in patients with untreated advanced non-small cell lung cancer (NSCLC). METHODS: Patients were randomized to the BTH1677 arm (N = 61; intravenous [IV] BTH1677, 4 mg/kg, weekly; IV bevacizumab, 15 mg/kg, once each 3-week cycle [Q3W]; IV carboplatin, 6 mg/mL/min Calvert formula area-under-the-curve, Q3W; and IV paclitaxel, 200 mg/m2 , Q3W) or Control arm (N = 31; bevacizumab/carboplatin/paclitaxel as above)...
February 27, 2018: Journal for Immunotherapy of Cancer
Jun Song, Sai-Jun Ma, Jian-Hua Luo, Hui Zhang, Ri-Xiong Wang, Hui Liu, Li Li, Zhi-Guang Zhang, Rui-Xiang Zhou
Globally, gastric cancer (GC) is one of the most common types of cancer and the third leading cause of cancer‑related death. In China, gastric and liver cancers have the highest mortality rates. Melatonin, also known as N-acetyl‑5-methoxytryptamine, is a hormone that is produced by the pineal gland in animals and regulates sleep and wakefulness. Melatonin has been shown to inhibit various carcinomas, including GC. There are many different hypotheses to explain the anticancer effects of melatonin, including stimulation of apoptosis, inhibition of cell growth, regulation of anticancer immunity, induction of free-radical scavenging, and the competitive inhibition of estrogen...
February 26, 2018: Oncology Reports
Zhi-Jian Han, Yan-Hu Feng, Bao-Hong Gu, Yu-Min Li, Hao Chen
SUMOylation is a reversible post-translational modification which has emerged as a crucial molecular regulatory mechanism, involved in the regulation of DNA damage repair, immune responses, carcinogenesis, cell cycle progression and apoptosis. Four SUMO isoforms have been identified, which are SUMO1, SUMO2/3 and SUMO4. The small ubiquitin-like modifier (SUMO) pathway is conserved in all eukaryotes and plays pivotal roles in the regulation of gene expression, cellular signaling and the maintenance of genomic integrity...
February 22, 2018: International Journal of Oncology
Song-Ming Ding, Ai-Li Lu, Wu Zhang, Lin Zhou, Hai-Yang Xie, Shu-Sen Zheng, Qi-Yong Li
Background: Our previous study showed that cancer-associated fibroblast MRC-5 promoted hepatocellular carcinoma progression by enhancing migration and invasion capability. However, few studies have explored the role of MRC-5 in pancreatic cancer (PC). In this study, we examined the exact role and associated mechanisms of MRC-5. Methods: The conditioned media for MRC-5 was used to culture PC cell lines SW1990 and PANC-1. Cell proliferation was compared based on colony formation assays of PC cells in normal media and of PC cells cultured with conditioned media of MRC-5...
2018: Journal of Cancer
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