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tumor immunological microenvironment

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
Boke Zhang, Yan Du, Yiqing He, Yiwen Liu, Guoliang Zhang, Cuixia Yang, Feng Gao
As a major component of the microenvironment of solid tumors, tumor-associated macrophages (TAMs) facilitate tumor progression. Intermediate-sized hyaluronan (INT-HA) fragments have an immunological function in cell differentiation; however, their role in promoting the polarization of non-activated macrophages to an M2-like TAM phenotype has not been characterized, and the underlying mechanisms remain unclear. Here, we used a miRNA microarray to find that some miRNAs (especially miR-935) were differentially regulated in INT-HA-induced M2-like macrophages...
October 19, 2018: Cancer Immunology, Immunotherapy: CII
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
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
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
Chiara Carone, Andrea Olivani, Raffaele Dalla Valle, Roberta Manuguerra, Enrico Maria Silini, Tommaso Trenti, Gabriele Missale, Elisabetta Cariani
Background: The antitumor immune response may play a major role in the clinical outcome of hepatocellular carcinoma (HCC). We characterized the liver immune microenvironment by direct hybridization of RNA extracted from HCC and nontumorous tissues. Methods: RNA was extracted from frozen liver tissue samples of HCC (T; n = 30) and nontumorous tissues (NT; n = 33) obtained from 38 patients. Matched samples were available for 25 patients. The immune gene expression profile was analyzed with the nCounter GX Human Immunology v2 system (NanoString Technologies), which detects the expression levels of 579 immune response-related genes simultaneously...
September 2018: Liver Cancer
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
Katharina Helene Susek, Maria Karvouni, Evren Alici, Andreas Lundqvist
Chemokines govern leukocyte migration by attracting cells that express their cognate ligands. Many cancer types show altered chemokine secretion profiles, favoring the recruitment of pro-tumorigenic immune cells and preventing the accumulation of anti-tumorigenic effector cells. This can ultimately result in cancer immune evasion. The manipulation of chemokine and chemokine-receptor signaling can reshape the immunological phenotypes within the tumor microenvironment in order to increase the therapeutic efficacy of cancer immunotherapy...
2018: Frontiers in Immunology
Yasuko Tada, Yosuke Togashi, Daisuke Kotani, Takeshi Kuwata, Eichi Sato, Akihito Kawazoe, Toshihiko Doi, Hisashi Wada, Hiroyoshi Nishikawa, Kohei Shitara
BACKGROUND: Several studies have established a correlation between the VEGF-VEGFR2 axis and an immunosuppressive microenvironment; this immunosuppression can be overcome by anti-angiogenic reagents, such as ramucirumab (RAM). However, little is known about the immunological impact of anti-angiogenic reagents within the tumor microenvironment in human clinical samples. This study aimed at investigating the effects of RAM on the tumor microenvironmental immune status in human cancers. METHODS: We prospectively enrolled 20 patients with advanced gastric cancer (GC) who received RAM-containing chemotherapy...
October 11, 2018: Journal for Immunotherapy of Cancer
Itay Ricon, Tsipi Hanalis-Miller, Rita Haldar, Rebecca Jacoby, Shamgar Ben-Eliyahu
Evidence suggests that excess perioperative activation of the sympathetic nervous system and the consequent release of catecholamines (ie, epinephrine and norepinephrine) in the context of cancer surgery and inflammation may significantly facilitate prometastatic processes. This review first presents biomedical processes that make the perioperative timeframe pivotal in determining long-term cancer outcomes nonproportionally to its short duration (days to weeks). Then, it analyzes the various mechanisms via which the excess release of catecholamines can facilitate the progression of cancer metastases in this context by directly affecting the malignant tissues and by regulating, via indirect pathways, immunological and other mechanisms that affect metastatic progression in the tumor microenvironment and systemically...
October 6, 2018: Cancer
Jingjing Duan, Yongwei Xie, Lijuan Qu, Lingxiong Wang, Shunkai Zhou, Yu Wang, Zhongyi Fan, Shengsheng Yang, Shunchang Jiao
BACKGROUND: Immunoscore, as a prognostic tool defined to quantify in situ immune cell infiltrates, appears to be superior to the TNM staging system. In esophageal squamous cell carcinoma (ESCC), no immunoscore has been established; however, in situ tumor immunology is recognized as highly important. Our study aimed to construct a comprehensive immunoprofile for ESCC. METHODS: The infiltration of four immune cell types (CD8+/CD4+/Foxp3+/CD33+ cells), the expression of both inhibitory (PD-1/PD-L1/Tim-3/LAG-3) and stimulatory checkpoints (OX-40/ICOS), and IDO1 were evaluated by IHC staining and multi-color immunofluorescence in two independent cohorts (95 patients in the primary cohort and 55 patients in the validation cohort)...
October 3, 2018: Journal for Immunotherapy of Cancer
Paola Kučan Brlić, Tihana Lenac Roviš, Guy Cinamon, Pini Tsukerman, Ofer Mandelboim, Stipan Jonjić
Poliovirus receptor (PVR, CD155) has recently been gaining scientific interest as a therapeutic target in the field of tumor immunology due to its prominent endogenous and immune functions. In contrast to healthy tissues, PVR is expressed at high levels in several human malignancies and seems to have protumorigenic and therapeutically attractive properties that are currently being investigated in the field of recombinant oncolytic virotherapy. More intriguingly, PVR participates in a considerable number of immunoregulatory functions through its interactions with activating and inhibitory immune cell receptors...
October 1, 2018: Cellular & Molecular Immunology
Cristina Maccalli, Kakil Ibrahim Rasul, Mamoun Elawad, Soldano Ferrone
Tumor lesions comprise multiple subpopulations of cells including those endowed with "stemness" properties. The latter cells are responsible of tumor initiation, metastasis formation, resistance to conventional therapies and disease recurrence. These relatively rare cells denominated cancer stem cells (CSCs) or cancer initiating cells (CICs) are defined based on self-renewing, multipotency and tumorigenicity. These cells through their immunomodulating features can evade from immunesurveillance, persisting in the form of quiescence and dormancy...
September 24, 2018: Seminars in Cancer Biology
Laura R Díaz, Elena Saavedra-López, Leire Romarate, Izaskun Mitxitorena, Paola V Casanova, George P Cribaro, José M Gallego, Ana Pérez-Vallés, Jerónimo Forteza-Vila, Clara Alfaro-Cervello, José M García-Verdugo, Carlos Barcia, Carlos Barcia
Since the proper activation of T cells requires the physical interaction with target cells through the formation of immunological synapses (IS), an alteration at this level could be a reason why tumors escape the immune response. As part of their life cycle, it is thought that T cells alternate between a static phase, the IS, and a dynamic phase, the immunological kinapse (IK), depending on high or low antigen sensing. Our investigation performed in tissue samples of human glioma shows that T cells are able to establish synapsing interactions not only with glioma tumorigenic cells, but also with stromal myeloid cells...
September 20, 2018: JCI Insight
Paolo A Ascierto, Reinhard Dummer
Recent developments in immunotherapy have prolonged overall survival in metastatic melanoma with the possibility to reach a long-term benefit. Targeted therapies based on BRAF and MEK inhibition also seem to have a long-term beneficial effect, which is more evident in patients with favorable baseline characteristics, namely normal levels of lactate dehydrogenase, without brain metastases, and low tumor burden. This long-term benefit of targeted therapies might be related to an immune-modulation: indeed BRAF and MEK inhibitors affect tumor microenvironment and immune surveillance, and it has been shown that patients with complete response to targeted treatment have a pre-existing favorable immunologic signature...
2018: Oncoimmunology
Di Huang, Jianing Chen, Linbin Yang, Qian Ouyang, Jiaqian Li, Liyan Lao, Jinghua Zhao, Jiang Liu, Yiwen Lu, Yue Xing, Fei Chen, Fengxi Su, Herui Yao, Qiang Liu, Shicheng Su, Erwei Song
Activation-induced cell death (AICD) of T lymphocytes can be exploited by cancers to escape immunological destruction. We demonstrated that tumor-specific cytotoxic T lymphocytes (CTLs) and type 1 helper T (TH 1) cells, rather than type 2 helper T cells and regulatory T cells, were sensitive to AICD in breast and lung cancer microenvironments. NKILA, an NF-κB-interacting long noncoding RNA (lncRNA), regulates T cell sensitivity to AICD by inhibiting NF-κB activity. Mechanistically, calcium influx in stimulated T cells via T cell-receptor signaling activates calmodulin, thereby removing deacetylase from the NKILA promoter and enhancing STAT1-mediated transcription...
October 2018: Nature Immunology
Subramanyam Dasari, Taruni Pandhiri, James Haley, Dean Lenz, Anirban K Mitra
Intercellular interactions play an important role in many biological processes, including tumor progression, immune responses, angiogenesis, and development. Paracrine or juxtacrine signaling mediates such interactions. The use of a conditioned medium and coculture studies are the most common methods to discriminate between these two types of interactions. However, the effect of localized high concentrations of secreted factors in the microenvironment during the paracrine interactions is not accurately recapitulated by conditioned medium and, thus, may lead to imprecise conclusions...
August 28, 2018: Journal of Visualized Experiments: JoVE
Shashi Gujar, Jonathan G Pol, Guido Kroemer
Immune checkpoint blockade is less efficient in patients bearing immunologically 'cold' tumors. Oncolytic viruses, which were originally discovered for their ability to preferentially kill malignant cells, can recondition the tumor microenvironment. Supporting this hypothesis, two new studies published in Science Translational Medicine show that adjuvant-like activities of oncolytic viruses make brain and breast tumors 'hot' and sensitize them for subsequent immune checkpoint blockade.
2018: Oncoimmunology
Katsutoshi Oda, Junzo Hamanishi, Koji Matsuo, Kosei Hasegawa
Ovarian clear cell carcinoma (OCCC) is distinctive from other histological types of epithelial ovarian cancer, with genetic/epigenetic alterations, a specific immune-related molecular profile, and epidemiologic associations with ethnicity and endometriosis. These findings allow for the exploration of unique and specific treatments for OCCC. Two major mutated genes in OCCC are PIK3CA and ARID1A, which are frequently coexistent with each other. Other genes' alterations also contribute to activation of the PI3K (e...
September 11, 2018: Gynecologic Oncology
Fei Zhao, Kathy Evans, Christine Xiao, Nicholas DeVito, Balamayooran Theivanthiran, Alisha Holtzhausen, Peter J Siska, Gerard C Blobe, Brent A Hanks
Although anti-PD-1 therapy has improved clinical outcomes for select patients with advanced cancer, many patients exhibit either primary or adaptive resistance to checkpoint inhibitor immunotherapy. The role of the tumor stroma in the development of these mechanisms of resistance to checkpoint inhibitors remains unclear. We demonstrated that pharmacologic inhibition of the TGFβ signaling pathway synergistically enhanced the efficacy of anti-CTLA-4 immunotherapy but failed to augment anti-PD-1/PD-L1 responses in an autochthonous model of BRAFV600E melanoma...
September 12, 2018: Cancer Immunology Research
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