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cancer immunological microenvironment

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
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
Elizabeth Ahern, Mark J Smyth, William C Dougall, Michele W L Teng
Recognizing that the transformative effects of immunotherapy are currently limited to a minority of patients with cancer, research efforts are increasingly focused on expanding and enhancing clinical responses by combining immunotherapies; the repurposing of existing drugs is an attractive approach, given their well-characterized safety and pharmacokinetic profiles. Receptor activator of nuclear factor-κB (RANK) and the RANK ligand (RANKL) were initially described in the context of T cell-dendritic cell interactions; however, the discovery of an obligate role of RANK signalling in osteoclastogenesis led to the development of the anti-RANKL antibody denosumab for antiresorptive indications, including bone metastases...
September 19, 2018: Nature Reviews. Clinical Oncology
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
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
Henry T Marshall, Mustafa B A Djamgoz
Host immunity recognizes and eliminates most early tumor cells, yet immunological checkpoints, exemplified by CTLA-4, PD-1, and PD-L1, pose a significant obstacle to effective antitumor immune responses. T-lymphocyte co-inhibitory pathways influence intensity, inflammation and duration of antitumor immunity. However, tumors and their immunosuppressive microenvironments exploit them to evade immune destruction. Recent PD-1 checkpoint inhibitors yielded unprecedented efficacies and durable responses across advanced-stage melanoma, showcasing potential to replace conventional radiotherapy regimens...
2018: Frontiers in Oncology
Marco C Merlano, Anna M Merlotti, Lisa Licitra, Nerina Denaro, Elena Fea, Danilo Galizia, Massimo Di Maio, Claudia Fruttero, Paola Curcio, Stefania Vecchio, Elvio G Russi, Renzo Corvò
Introduction and background: Second-line treatment of platinum-resistant relapsed/metastatic (R/M) head and neck cancer (HNC) is a currently unmet clinical need. Clinical trials showed improvement in overall survival and quality of life of R/M-HNC patients treated with anti-PD-1 regardless of the number of prior chemotherapy lines; however, the percentage of long-term survivors remains limited.This study aims to test the hypothesis that attacking the tumor microenvironment at multiple levels can increase immunogenicity of R/M-HNC without worsening the safety profile of immune checkpoint inhibitors...
August 2018: Clinical and Translational Radiation Oncology
Patrycja Piętak, Natalia Pietrzyk, Anna Pawłowska, Dorota Suszczyk, Wiesława Bednarek, Jan Kotarski, Iwona Wertel
Ovarian cancer is a serious diagnostic and clinical issue. It belongs to the group of cancers with the highest mortality rate, that is why new, effective methods of therapy have been sought after. In recent years, researchers have been paying attention to the use of immunothetapy in the treatment of ovarian cancer. Currently, the numer of studies with the use of PD-1/PD-L1 pathway inhibitors is increasing. It has been reported that PD-1 receptor and its ligand are expressed on tumor cells and immunology system cells in patients with ovarian cancer...
2018: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
Margherita Ratti, Andrea Lampis, Jens C Hahne, Rodolfo Passalacqua, Nicola Valeri
Gastric cancer is one of the most aggressive malignancies, with limited treatment options in both locally advanced and metastatic setting, resulting in poor prognosis. Based on genomic characterization, stomach tumour has recently been described as a heterogeneous disease composed by different subtypes, each of them with peculiar molecular aspects and specific clinical behaviour. With an incidence of 22% among all western gastric tumour cases, stomach cancer with microsatellite instability was identified as one of these subgroups...
November 2018: Cellular and Molecular Life Sciences: CMLS
Daniel Eyraud, Benjamin Granger, Armelle Bardier, Yann Loncar, GaËlle Gottrand, Gilles Le Naour, Jean-Michel Siksik, Jean-Christophe Vaillant, David Klatzmann, Louis Puybasset, Frederic Charlotte, Jeremy Augustin
Cancer research has moved from investigating tumour cells to including analysis of the tumour microenvironment as well. The aim of this study was to assess the cellular infiltrate of colorectal cancer (CRC) using computer-aided analysis of whole slide digital image derived from tissue microarray (TMA). TMA slides from 31 CRC patients were immunostained for forkhead box protein 3 (FOXP3) and immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO) at four sites: centre (C) and invasive front (F) of the tumour, proximal non-metastatic draining lymph node (N-), tumour-draining lymph node with metastasis (N+) and healthy mucosa at 10 cm from the cancer (M)...
August 27, 2018: Pathology
Shivani Jain, Rashmi Gs Phulari, Rajendrasinh Rathore, Arpan K Shah, Sankalp Sancheti
Background: Oral squamous cell carcinoma (OSCC) is the most common cancer of the oral cavity. Tumor stage, thickness, lymph node metastasis (LNM), extranodal spread, perineural invasion, tumor differentiation, mutations, human papillomavirus infection and tumor microenvironment are independent prognostic indicators of OSCC. However, clinically, among all factors, LNM is considered an important prognostic factor in OSCC as it not only determines the stage of disease but also the strongest independent factor which predicts recurrence of disease...
May 2018: Journal of Oral and Maxillofacial Pathology: JOMFP
Aitziber Buqué, Lorenzo Galluzzi
Figure 1. Main Applications of Mouse Models for Tumor Immunology and Immunotherapy. Immunodeficient mice xenografted with human cancer cell lines have been at the foundation of in vivo cancer research for several decades, providing ground for the regulatory approval of multiple chemotherapeutics and targeted anticancer agents, but are intrinsically unsuitable for studying tumor immunology and immunotherapy. Similarly, patient-derived xenografts (PDXs) established in immunodeficient mice are not subjected to immunosurveillance by the host, although (depending on the protocol employed for PDX generation) some components of the patient's immune system may also be transferred to the mouse and be active, at least for some time...
September 2018: Trends in Cancer
Yu-Tzu Tai, Shih-Feng Cho, Kenneth C Anderson
Immunomodulatory drugs and monoclonal antibody-based immunotherapies have significantly improved the prognosis of the patients with multiple myeloma (MM) in the recent years. These new classes of reagents target malignant plasma cells (PCs) and further modulate the immune microenvironment, which prolongs anti-MM responses and may prevent tumor occurrence. Since MM remains an incurable cancer for most patients, there continues to be a need to identify new tumor target molecules and investigate alternative cellular approaches using gene therapeutic strategies and novel treatment mechanisms...
2018: Frontiers in Immunology
Luciana Barros, Marco Antonio Pretti, Leonardo Chicaybam, Luiza Abdo, Mariana Boroni, Martin Hernán Bonamino
The immunologic landscape of tumors has been continuously unveiled, providing a new look at the interactions between cancer cells and the immune system. Emerging tumor cells are constantly eliminated by the immune system, but some cells establish a long-term equilibrium phase leading to tumor immunoediting and, eventually, evasion. During this process, tumor cells tend to acquire more mutations. Bearing a high mutation burden leads to a greater number of neoantigens with the potential to initiate an immune response...
August 20, 2018: Clinics
Jonas Steenbrugge, Koen Breyne, Kristel Demeyere, Olivier De Wever, Niek N Sanders, Wim Van Den Broeck, Cecile Colpaert, Peter Vermeulen, Steven Van Laere, Evelyne Meyer
BACKGROUND: Murine breast cancer models relying on intraductal tumor cell inoculations are attractive because they allow the study of breast cancer from early ductal carcinoma in situ to metastasis. Using a fully immunocompetent 4T1-based intraductal model for triple-negative breast cancer (TNBC) we aimed to investigate the immunological responses that guide such intraductal tumor progression, focusing on the prominent role of macrophages. METHODS: Intraductal inoculations were performed in lactating female mice with luciferase-expressing 4T1 mammary tumor cells either with or without additional RAW264...
August 15, 2018: Journal of Experimental & Clinical Cancer Research: CR
Yutaka Kawakami
Clinical trials for immune-checkpoint inhibitors and T cell-based adoptive cell therapy have demonstrated robust clinical responses in some patients with advanced cancer of various types, including hematological malignancies. However, response rates to PD-1/PD-L1 blockade are about 10%-30% in most cancer types. To improve the efficacy of immunotherapy, combination immunotherapy using other standard cancer therapies (e.g., chemotherapy, target therapy, and radiation) and various immune modulators for crucial regulation points in antitumor T-cell responses (e...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Eva Reijmen, Luca Vannucci, Marijke De Couck, Jacques De Grève, Yori Gidron
Accumulating evidence points to a beneficial effect ofvagus nerve activity in tumor development. The vagus nerve is proposed to slow tumorigenesis because of its anti-inflammatory properties mediated through ACh and the α7nAChR. Since α7nAChRs are widely expressed by many types of immune cells we hypothesized that the vagus nerve affects the tumor microenvironment and anticancer immunity. We found direct evidence in studies using animal cancer models that vagus nerve stimulation alters immunological responses relevant to the tumor microenvironment...
August 2, 2018: Immunology Letters
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