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Cancer AND Immunology

M De Santis
BACKGROUND: Prostate cancer (PCA) seems to be more of an immunologic desert than other tumor entities. It is striking that only rarely does prostate cancer show abundant immune cells and a proimmunogenic microenvironment. OBJECTIVES: Is immunotherapy in PCA effective and which patients can benefit. MATERIALS AND METHODS: A review of the literature and recent congress data are presented. RESULTS: Preliminary results with sipuleucel-T for PCA cancer were very promising showing a significant overall survival benefit in randomised phase III studies and the US Federal Drug Administration (FDA) approval for this individualised vaccine...
October 19, 2018: Der Urologe. Ausg. A
Bradlee L Heckmann, Bart Tummers, Douglas R Green
Programmed cell death (PCD) plays critical roles in development, homeostasis, and both control and progression of a plethora of diseases, including cancer and neurodegenerative pathologies. Besides classical apoptosis, several different forms of PCD have now been recognized, including necroptosis. The way a cell dies determines the reaction of the surrounding environment, and immune activation in response to cell death proceeds in a manner dependent on which death pathways are activated. Apoptosis and necroptosis are major mechanisms of cell death that typically result in opposing immune responses...
October 19, 2018: Cell Death and Differentiation
Annacarmen Petrizzo, Maria Tagliamonte, Angela Mauriello, Valerio Costa, Marianna Aprile, Roberta Esposito, Andrea Caporale, Antonio Luciano, Claudio Arra, Maria Lina Tornesello, Franco M Buonaguro, Luigi Buonaguro
BACKGROUND: A novel prediction algorithm is needed for the identification of effective tumor associated mutated neoantigens. Only those with no homology to self wild type antigens are true predicted neoantigens (TPNAs) and can elicit an antitumor T cell response, not attenuated by central tolerance. To this aim, the mutational landscape was evaluated in HCV-associated hepatocellular carcinoma. METHODS: Liver tumor biopsies and adjacent non-tumor liver tissues were obtained from 9 HCV-chronically infected subjects and subjected to RNA-Seq analysis...
October 19, 2018: Journal of Translational Medicine
Andreas Sperlich, Alexander Balmert, Dietrich Doll, Sabine Bauer, Fabian Franke, Gisela Keller, Dirk Wilhelm, Anna Mur, Michael Respondek, Helmut Friess, Ulrich Nitsche, Klaus-Peter Janssen
BACKGROUND: Even though the post-operative outcome varies greatly among patients with nodal positive colon cancer (UICC stage III), personalized prediction of systemic disease recurrence is currently insufficient. We investigated in a retrospective setting whether genetic and immunological biomarkers can be applied for stratification of distant metastasis occurrence risk. METHODS: Eighty four patients with complete resection (R0) of stage III colon cancer from two clinical centres were analysed for genetic biomarkers: microsatellite instability, oncogenic mutations in KRAS exon2 and BRAF exon15, expression of osteopontin and the metastasis-associated genes SASH1 and MACC1...
October 19, 2018: BMC Cancer
Maria Soler, Xiaokang Li, Aurelian John-Herpin, Julien Schmidt, George Coukos, Hatice Altug
The screening and analysis of T cells functional avidity for specific tumor-associated antigens is crucial for the development of personalized immunotherapies against cancer. The affinity and kinetics of a T cell receptor (TCR) binding to the peptide-major histocompatibility complex (pMHC), expressed on tumor or antigen-presenting cells, have shown major implications in T cell activation and effector functions. We introduce an innovative methodology for the two-dimensional affinity analysis of TCR-pMHC in a label-free configuration by employing a multiparametric Surface Plasmon Resonance biosensor (MP-SPR) functionalized with artificial cell membranes...
October 19, 2018: ACS Sensors
Dayson Moreira, Tomasz Adamus, Xingli Zhao, Yu-Lin Su, Zhuoran Zhang, Seok Voon White, Piotr Swiderski, Xin Lu, Ronald A DePinho, Sumanta K Pal, Marcin Kortylewski
Purpose: Prostate cancers show remarkable resistance to emerging immunotherapies, partly due to tolerogenic STAT3 signaling in tumor-associated myeloid cells. Here, we describe a novel strategy combining STAT3 inhibition with Toll-like Receptor 9 (TLR9) stimulation to unleash immune response against prostate cancers regardless of the genetic background. Experimental Design: We developed and validated a conjugate of the STAT3 antisense oligonucleotide (ASO) tethered to immunostimulatory TLR9 agonist (CpG oligonucleotide) to improve targeting of human and mouse prostate cancer and myeloid immune cells, such as myeloid-derived suppressor cells (MDSC)...
October 18, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Yoshinaga Okugawa, Yuji Toiyama, Akira Yamamoto, Tsunehiko Shigemori, Ayame Kitamura, Takashi Ichikawa, Shozo Ide, Takahito Kitajima, Hiroyuki Fujikawa, Hiromi Yasuda, Yoshiki Okita, Junichiro Hiro, Toshimitsu Araki, Donald C McMillan, Chikao Miki, Masato Kusunoki
BACKGROUND: The systemic inflammatory response (SIR) via host-tumor interactions has been termed the seventh hallmark of cancer, and several studies demonstrated that SIR might be a pivotal mediator for progression of cancer cachexia. The objective of this study was to clarify the correlation between sarcopenia and SIR in patients with colorectal cancer (CRC). METHODS: A total of 308 patients with CRC were enrolled in this study. Preoperative psoas muscle mass index and intramuscular adipose tissue content were evaluated using preoperative computed tomographic images, and the correlation between body composition status and several SIR markers, including C-reactive protein (CRP), serum albumin level, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and systemic immune-inflammation index (SII) was assessed using statistical methods...
October 18, 2018: JPEN. Journal of Parenteral and Enteral Nutrition
T Bopp, H Schild
Understanding the fundamental principles underlying the development, activation, regulation, plasticity, diversification, and even death of immune cells is a prerequisite for the development of targeted strategies to modulate the immune system in the fight against cancer. As our understanding of these processes evolves, their translation has led to the development of pioneering therapeutic approaches in the treatment of malignant diseases.
October 16, 2018: Der Pathologe
Ulrike Haug
Colon cancer is currently the third leading cause of cancer death in men and women in Germany, with a total of about 25,000 deaths per year. Established methods for early detection of colorectal cancer include lower gastrointestinal endoscopy and fecal occult blood testing. For both procedures, there is evidence of a reduction in colorectal cancer-specific mortality and for endoscopy a reduction of colorectal cancer incidence has been shown.In Germany, the guaiac test for fecal occult blood has been offered since 1977...
October 16, 2018: Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz
Wouter W van Willigen, Martine Bloemendal, Winald R Gerritsen, Gerty Schreibelt, I Jolanda M de Vries, Kalijn F Bol
Immune checkpoint inhibitors propelled the field of oncology with clinical responses in many different tumor types. Superior overall survival over chemotherapy has been reported in various metastatic cancers. Furthermore, prolonged disease-free and overall survival have been reported in the adjuvant treatment of stage III melanoma. Unfortunately, a substantial portion of patients do not obtain a durable response. Therefore, additional strategies for the treatment of cancer are still warranted. One of the numerous options is dendritic cell vaccination, which employs the central role of dendritic cells in activating the innate and adaptive immune system...
2018: Frontiers in Immunology
Jordan Aldersley, David R Lorenz, Vikas Misra, Hajime Uno, Dana Gabuzda
OBJECTIVE(S): HIV-positive individuals have elevated rates of anal squamous cell carcinoma (SCC), and sexually transmitted infections with its causative agent, high-risk human papillomavirus, and other oncoviruses including hepatitis B virus (HBV). HBV infection can cause liver cancer, and has been associated with increased risk of some extra-hepatic cancers including biliary tract cancer, pancreatic cancer, and non-Hodgkin lymphoma. Whether HBV is associated with anal SCC risk is unknown...
October 16, 2018: AIDS
Liannv Qiu, Qinhua Yu, Yonglie Zhou, Sujie Zheng, Jiaojiao Tao, Qian Jiang, Guorong Yuan
Non-small cell lung cancer (NSCLC) represents one of the most common and aggressive cancers worldwide, as it typically displays irreversible progression and poor prognosis. The interaction between programmed cell death 1 (PD-1) and its ligand, PD-L1, plays important roles in tumor immunology. Follicular helper T (Tfh) cells have characteristically high PD-1 expression; thus, in the present study, we investigated the role of circulating Tfh cells and their correlation with disease-free survival after tumor resection in NSCLC...
October 16, 2018: Cancer Science
Premal H Thaker, Nicholas Borys, Jason Fewell, Khursheed Anwer
GEN-1 is a gene-based immunotherapy, comprising a human IL-12 gene expression plasmid and a synthetic plasmid delivery system, delivered intraperitoneally (ip.) to produce local and persistent levels of a pleiotropic immunocytokine, IL-12, at the tumor site in patients with advanced ovarian cancer. The goal of local and persistent IL-12 delivery is to remodel the highly immunosuppressive tumor microenvironment to favor immune stimulation while avoiding serious systemic toxicities, a major limitation of recombinant IL-12 therapy...
October 16, 2018: Future Oncology
Joan Campbell-Tofte, Aristidis Vrahatis, Knud Josefsen, Jesper Mehlsen, Kaj Winther
In contrast to the insidious and poorly immunogenic human papillomavirus (HPV) infections, vaccination with the HPV virus-like particles (vlps) is non-infectious and stimulates a strong neutralizing-antibody response that protects HPV-naïve vaccinees from viral infection and associated cancers. However, controversy about alleged adverse events following immunization (AEFI) with the vlps have led to extensive reductions in vaccine acceptance, with countries like Japan dropping it altogether. The AEFIs are grouped into chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)...
October 16, 2018: Cellular and Molecular Life Sciences: CMLS
Mirco Di Marco, Alice Ramassone, Sara Pagotto, Eleni Anastasiadou, Angelo Veronese, Rosa Visone
Autoimmunity and hematological malignancies are often concomitant in patients. A causal bidirectional relationship exists between them. Loss of immunological tolerance with inappropriate activation of the immune system, likely due to environmental and genetic factors, can represent a breeding ground for the appearance of cancer cells and, on the other hand, blood cancers are characterized by imbalanced immune cell subsets that could support the development of the autoimmune clone. Considerable effort has been made for understanding the proteins that have a relevant role in both processes; however, literature advances demonstrate that microRNAs (miRNAs) surface as the epigenetic regulators of those proteins and control networks linked to both autoimmunity and hematological malignancies...
October 12, 2018: International Journal of Molecular Sciences
Ravi A Madan, James L Gulley
No abstract text is available yet for this article.
October 13, 2018: Journal of the National Cancer Institute
Paul R Walker
The stroma of solid tumors can exclude or limit immune infiltration, or lead to the recruitment of tumor-promoting rather than tumor-attacking immune cells. This finding was reported by Jayaprakash et al. in this issue of the JCI, and it was particularly prominent in the hypoxic zones of tumors in the transgenic adenocarcinoma of the mouse prostate (TRAMP) cancer models. A current clinical goal of immune checkpoint blockade (ICB) is to extend its utility to more patients by converting immunologically "cold" tumors that do not provoke a strong immunological response to "hot" tumors that are invaded by swarms of T cells...
October 15, 2018: Journal of Clinical Investigation
Daniel M Altmann
The field of cancer immunology stepped into the limelight this year when James P. Allison and Tasuku Honjo received the Nobel Prize in Physiology or Medicine for their discovery of cancer therapy by inhibition of negative immune regulation. Among many exciting advances contributing to the coming of age of tumour immunology as a viable clinical specialty has been the ability to progress from the initial elucidation of tumour antigens, such as the melanoma antigen, MAGE-1, to high-throughput sequencing facilitating identification of T cell epitopes from diverse tumour neoantigens...
November 2018: Immunology
Yi-Jun Wang, Rochelle Fletcher, Jian Yu, Lin Zhang
Emerging evidence suggests that the clinical success of conventional chemotherapy is not solely attributed to tumor cell toxicity, but also results from the restoration of immunosurveillance, which has been largely neglected in the past preclinical and clinical research. Antitumor immune response can be primed by immunogenic cell death (ICD), a type of cell death characterized by cell-surface translocation of calreticulin (CRT), extracellular release of ATP and high mobility group box 1 (HMGB1), and stimulation of type I interferon (IFN) responses...
September 2018: Genes & Diseases
Suneel D Kamath, Priya U Kumthekar
While the CNS has long been viewed as an immune-privileged environment, a paradigm shift in neuro-immunology has elevated the role of systemic immunotherapy for the treatment of metastatic disease. Increasing knowledge regarding the presence of a CNS lymphatic system and the physical and biochemical alteration of the blood brain barrier (BBB) by the tumor microenvironment suggests immune cell trafficking in and out of the CNS is possible. Emerging clinical data suggest immune checkpoint inhibitors (ICIs) can stimulate T cells peripherally to in turn have anti-tumor effects in the CNS...
2018: Frontiers in Oncology
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