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https://www.readbyqxmd.com/read/28342985/mast-cells-are-directly-activated-by-contact-with-cancer-cells-by-a-mechanism-involving-autocrine-formation-of-adenosine-and-autocrine-paracrine-signaling-of-the-adenosine-a3-receptor
#1
Yaara Gorzalczany, Eyal Akiva, Ofir Klein, Ofer Merimsky, Ronit Sagi-Eisenberg
Mast cells (MCs) constitute an important part of the tumor microenvironment (TME). However, their underlying mechanisms of activation within the TME remain poorly understood. Here we show that recapitulating cell-to-cell contact interactions by exposing MCs to membranes derived from a number of cancer cell types, results in MC activation, evident by the increased phosphorylation of the ERK1/2 MAP kinases and Akt, in a phosphatidylinositol 3-kinase dependent fashion. Activation is unidirectional since MC derived membranes do not activate cancer cells...
March 22, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28334399/association-of-hiv-status-with-local-immune-response-to-anal-squamous-cell-carcinoma-implications-for-immunotherapy
#2
Elizabeth L Yanik, Genevieve J Kaunitz, Tricia R Cottrell, Farah Succaria, Tracee L McMiller, Maria L Ascierto, Jessica Esandrio, Haiying Xu, Aleksandra Ogurtsova, Toby Cornish, Evan J Lipson, Suzanne L Topalian, Eric A Engels, Janis M Taube
Importance: The programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) pathway play an important immunosuppressive role in cancer and chronic viral infection, and have been effectively targeted in cancer therapy. Anal squamous cell carcinoma (SCC) is associated with both human papillomavirus and HIV infection. To date, patients with HIV have been excluded from most trials of immune checkpoint blocking agents, such as anti-PD-1 and anti-PD-L1, because it was assumed that their antitumor immunity was compromised compared with immunocompetent patients...
March 23, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28331617/current-approaches-to-increase-car-t-cell-potency-in-solid-tumors-targeting-the-tumor-microenvironment
#3
REVIEW
Irene Scarfò, Marcela V Maus
Chimeric antigen receptor (CAR) T-cell therapy represents a revolutionary treatment for haematological malignancies (i.e. B-ALL). However, the success of this type of treatment has not yet been achieved in solid tumors. One hypothesis is that the immunosuppressive nature of the tumor microenvironment (TME) influences and affects the efficacy of adoptive immunotherapy. Understanding the role of the TME and its interaction with CAR T-cells is crucial to improve the potency of adoptive immunotherapy. In this review, we discuss the strategies and potential combinatorial approaches recently developed in mouse models to enhance the efficacy of CAR T-cells, with particular emphasis on the translational potential of these approaches...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28323500/strategies-to-target-glucose-metabolism-in-tumor-microenvironment-on-cancer-by-flavonoids
#4
Gang Wang, Jun-Jie Wang, Rui Guan, Li Du, Jing Gao, Xing-Li Fu
The imbalance between glucose metabolism and cancer cell growth in tumor microenvironment (TME), which are closely related with the occurrence and progression of cancer. Accumulating evidence has demonstrated that flavonoids exert many biological properties, including antioxidant and anticarcinogenic activities. Recently, the roles and applications of flavonoids, particularly in relation to glucose metabolism in cancers, have been highlighted. Thus, the identification of flavonoids targeting alternative glucose metabolism pathways in TME may represent an attractive approach to the more effective therapeutic strategies for cancer...
March 21, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28323111/nanoparticles-for-tumor-immunotherapy
#5
REVIEW
Xinlong Zang, Xiuli Zhao, Haiyang Hu, Mingxi Qiao, Yihui Deng, Dawei Chen
Although most researches and therapies have been focused on the tumor itself, it is becoming clear that immune cells can not only suppress tumor development but support and maintain their malignant type. Promising recent developments in immunology will provide opportunities for tumor-specific immunotherapy, which can orchestrate the patients immune system to target, fight and eradicate cancer cells without destroying healthy cells. However, antitumor immunity driven by self-immune system alone may be therapeutically insufficient...
March 18, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28318643/cxcl10-alters-the-tumour-immune-microenvironment-and-disease-progression-in-a-syngeneic-murine-model-of-high-grade-serous-ovarian-cancer
#6
Katrina K Au, Nichole Peterson, Peter Truesdell, Gillian Reid-Schachter, Kasra Khalaj, Runhan Ren, Julie-Ann Francis, Charles H Graham, Andrew W Craig, Madhuri Koti
OBJECTIVE: We recently established that high STAT1 expression and associated T helper type I tumour immune microenvironment (TME) are prognostic and chemotherapy response predictive biomarkers in high-grade serous ovarian cancer (HGSC). STAT1 induced chemokine CXCL10 is key to the recruitment of lymphocytes in the TME and is significantly highly expressed in the tumours from patients with longer survival. In the current study we therefore aimed to elucidate the role CXCL10 in disease progression and tumour immune transcriptomic alterations using the ID8 syngeneic murine model of HGSC...
March 16, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28315018/influence-of-pelvic-volume-on-surgical-outcome-after-low-anterior-resection-for-rectal-cancer
#7
G Zur Hausen, J Gröne, D Kaufmann, S M Niehues, K Aschenbrenner, A Stroux, B Hamm, M E Kreis, Johannes C Lauscher
BACKGROUND: Low anterior resection (LAR) for rectal cancer is a potentially challenging operation due to limited space in the pelvis. CT pelvimetry allows to quantify pelvic space, so that its relationship with outcome after LAR may be assessed. Studies investigating this, however, yielded conflicting results. We hypothesized that a small pelvis is associated with a higher rate of incomplete mesorectal excision, anastomotic leakages, and increased rate of urinary dysfunction in patients operated for rectal cancer...
March 18, 2017: International Journal of Colorectal Disease
https://www.readbyqxmd.com/read/28292436/the-microenvironmental-landscape-of-brain-tumors
#8
REVIEW
Daniela F Quail, Johanna A Joyce
The brain tumor microenvironment (TME) is emerging as a critical regulator of cancer progression in primary and metastatic brain malignancies. The unique properties of this organ require a specific framework for designing TME-targeted interventions. Here, we discuss a number of these distinct features, including brain-resident cell types, the blood-brain barrier, and various aspects of the immune-suppressive environment. We also highlight recent advances in therapeutically targeting the brain TME in cancer...
March 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28292326/immune-mediators-in-the-tumor-microenvironment-of-prostate-cancer
#9
REVIEW
Jinlu Dai, Yi Lu, Hernan Roca, Jill M Keller, Jian Zhang, Laurie K McCauley, Evan T Keller
Prostate cancer tissue is composed of both cancer cells and host cells. The milieu of host components that compose the tumor is termed the tumor microenvironment (TME). Host cells can be those derived from the tissue in which the tumor originates (e.g., fibroblasts and endothelial cells) or those recruited, through chemotactic or other factors, to the tumor (e.g., circulating immune cells). Some immune cells are key players in the TME and represent a large proportion of non-tumor cells found within the tumor...
March 14, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28291841/prognosis-of-locally-advanced-rectal-cancer-can-be-predicted-more-accurately-using-pre-and-post-chemoradiotherapy-neutrophil-lymphocyte-ratios-in-patients-who-received-preoperative-chemoradiotherapy
#10
SooYoon Sung, Seok Hyun Son, Eun Young Park, Chul Seung Kay
PURPOSE: The neutrophil-lymphocyte ratio (NLR) has been suggested as an inflammation-related factor, but also as an indicator of systemic anti-tumor immunity. We aimed to evaluate the prognostic value of the NLR and to propose a proper cut-off value in patients with locally advanced rectal cancer who received preoperative chemoradiation (CRT) followed by curative total mesorectal excision (TME). METHODS: A total of 110 rectal cancer patients with clinical T3-4 or node-positive disease were retrospectively analyzed...
2017: PloS One
https://www.readbyqxmd.com/read/28288136/oncostatin-m-promotes-cancer-cell-plasticity-through-cooperative-stat3-smad3-signaling
#11
D J Junk, B L Bryson, J M Smigiel, N Parameswaran, C A Bartel, M W Jackson
Increasing evidence supports the idea that cancer cell plasticity promotes metastasis and tumor recurrence, resulting in patient mortality. While it is clear that the tumor microenvironment (TME) contributes to cancer cell plasticity, the specific TME factors most actively controlling plasticity remain largely unknown. Here, we performed a screen to identify TME cytokines and growth factors that promote epithelial-mesenchymal plasticity, and acquisition of cancer stem cell (CSC) properties. Of 28 TME cytokines and growth factors tested, we identified Oncostatin M (OSM) as the most potent inducer of mesenchymal/CSC properties...
March 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28282575/sorafenib-combined-with-her-2-targeted-vaccination-can-promote-effective-t-cell-immunity-in-vivo
#12
Melek M E Sunay, Jeremy B Foote, James M Leatherman, Justin P Edwards, Todd D Armstrong, Christopher J Nirschl, Jessica Hicks, Leisha A Emens
The tumor microenvironment (TME) is established and maintained through complex interactions between tumor cells and host stromal elements. Therefore, therapies that target multiple cellular components of the tumor may be most effective. Sorafenib, a multi-kinase inhibitor, alters signaling pathways in both tumor cells and host stromal cells. Thus, we explored the potential immune-modulating effects of sorafenib in a murine HER-2-(neu) overexpressing breast tumor model alone and in combination with a HER-2 targeted granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting vaccine (3T3neuGM)...
March 7, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28281474/combined-laparoscopic-and-transanal-total-mesorectal-excision-for-rectal-cancer-initial-experience-and-early-results
#13
Morten Holt Thomsen, Henrik Ovesen, Jens Ravn Eriksen
INTRODUCTION: Incomplete specimens resulting in residual mesorectum in the patient and an increased risk of local recurrence remains a problem. We have introduced transanal-total mesorectal excision (Ta-TME) in our department to potentially overcome this problem due to more direct access to the lower pelvis in patients undergoing TME for rectal cancer and this article presents our initial experience with the new procedure. MATERIALS AND METHODS: Patients with a T1-T3 mid or low rectal cancer eligible for TME or intersphincteric abdominoperineal excision were selected for a combined transanal and transabdominal laparoscopic resection...
April 2017: Journal of Minimal Access Surgery
https://www.readbyqxmd.com/read/28280037/local-activation-of-p53-in-the-tumor-microenvironment-overcomes-immune-suppression-and-enhances-antitumor-immunity
#14
Gang Guo, Miao Yu, Wei Xiao, Esteban Celis, Yan Cui
Mutations in tumor suppressor p53 remain a vital mechanism of tumor escape from apoptosis and senescence. Emerging evidence suggests that p53 dysfunction also fuels inflammation and supports tumor immune evasion, thereby serving as an immunological driver of tumorigenesis. Therefore, targeting p53 in the tumor microenvironment (TME) also represents an immunologically desirable strategy for reversing immunosuppression and enhancing antitumor immunity. Using a pharmacological p53 activator nutlin-3a, we show that local p53 activation in TME comprising overt tumor infiltrating leukocytes (TILeus) induces systemic antitumor immunity and tumor regression, but not in TME with scarce TILeus, such as B16 melanoma...
March 9, 2017: Cancer Research
https://www.readbyqxmd.com/read/28277613/activation-of-mutated-trpa1-ion-channel-by-resveratrol-in-human-prostate-cancer-associated-fibroblasts-caf
#15
Eric Vancauwenberghe, Lucile Noyer, Sandra Derouiche, Loïc Lemonnier, Pierre Gosset, Laura R Sadofsky, Pascal Mariot, Marine Warnier, Alexandre Bokhobza, Christian Slomianny, Brigitte Mauroy, Jean-Louis Bonnal, Etienne Dewailly, Philippe Delcourt, Laurent Allart, Natalia Prevarskaya, Morad Roudbaraki
Previous studies showed the effects of resveratrol (RES) on several cancer cells, including prostate cancer (PCa) cell apoptosis without taking into consideration the impact of the tumor microenvironment (TME). The TME is composed of cancer cells, endothelial cells, blood cells and cancer-associated fibroblasts (CAF), the main source of growth factors. The latter cells might modify in the TME the impact of RES on tumor cells via secreted factors. Recent data clearly show the impact of CAF on cancer cells apoptosis resistance via secreted factors...
March 9, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28275576/the-unique-molecular-and-cellular-microenvironment-of-ovarian-cancer
#16
REVIEW
Thomas Worzfeld, Elke Pogge von Strandmann, Magdalena Huber, Till Adhikary, Uwe Wagner, Silke Reinartz, Rolf Müller
The reciprocal interplay of cancer cells and host cells is an indispensable prerequisite for tumor growth and progression. Cells of both the innate and adaptive immune system, in particular tumor-associated macrophages (TAMs) and T cells, as well as cancer-associated fibroblasts enter into a malicious liaison with tumor cells to create a tumor-promoting and immunosuppressive tumor microenvironment (TME). Ovarian cancer, the most lethal of all gynecological malignancies, is characterized by a unique TME that enables specific and efficient metastatic routes, impairs immune surveillance, and mediates therapy resistance...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28271268/robotic-versus-laparoscopic-rectal-resection-for-sphincter-saving-surgery-pathological-and-short-term-outcomes-in-a-single-center-analysis-of-130-consecutive-patients
#17
Alain Valverde, Nicolas Goasguen, Olivier Oberlin, Magali Svreck, Jean-François Fléjou, Alain Sezeur, Henri Mosnier, Rémi Houdart, Renato M Lupinacci
BACKGROUND: Minimally invasive sphincter-saving rectal resection represents a challenging procedure. Robotic surgery for rectal cancer has several advantages over conventional surgery in performing precise dissection and was proved to be safe and effective in previous studies. However, comparison between laparoscopic and robotic rectal resection has drawn contradictory results. The aim of the present study was to compare robotic and laparoscopic sphincter-saving rectal resections for short-term and pathological outcomes...
March 7, 2017: Surgical Endoscopy
https://www.readbyqxmd.com/read/28271267/prior-experience-in-laparoscopic-rectal-surgery-can-minimise-the-learning-curve-for-robotic-rectal-resections-a-cumulative-sum-analysis
#18
Manfred Odermatt, Jamil Ahmed, Sofoklis Panteleimonitis, Jim Khan, Amjad Parvaiz
BACKGROUND: The learning curve for robotic colorectal surgery is ill-defined. This study aimed to investigate the learning curve of experienced laparoscopic rectal surgeons when starting with robotic total mesorectal excision (TME) using cumulative sum (CUSUM) charts. METHODS: This retrospective case series analysed patients who underwent curative and elective laparoscopic or robotic TMEs for rectal cancer performed by two surgeons. The first consecutive robotic TME cases of each surgeon were 1:1 propensity score matched to their laparoscopic TME cases using age, body mass index, American Society of Anesthesiologists grade, T stage (AJCC) and tumour location height...
March 7, 2017: Surgical Endoscopy
https://www.readbyqxmd.com/read/28270089/tissue-elasticity-bridges-cancer-stem-cells-to-the-tumor-microenvironment-through-micrornas-implications-for-a-watch-and-wait-approach-to-cancer
#19
Shengwen Calvin Li, Long T Vu, Jane Jianying Luo, Jiang F Zhong, Zhongjun Li, Brent A Dethlefs, William G Loudon, Mustafa H Kabeer
Targeting the tumor microenvironment (TME) through which cancer stem cells (CSCs) crosstalk for cancer initiation and progression, may open up new treatments different from those centered on the original hallmarks of cancer genetics thereby implying a new approach for suppression of TME-driven activation of CSCs. Cancer is dynamic, heterogeneous, evolving with the TME and can be influenced by tissue-specific elasticity. One of the mediators and modulators of the crosstalk between CSCs and mechanical forces is miRNA, which can be developmentally regulated, tissue- and cell-specific...
March 6, 2017: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28265766/combined-transanal-total-mesorectal-excision-tatme-with-laparoscopic-instruments-and-abdominal-robotic-surgery-in-rectal-cancer
#20
R Bravo, J-S Trépanier, M C Arroyave, M Fernández-Hevia, A Pigazzi, A M Lacy
Laparoscopic surgery for rectal cancer can be technically challenging. We describe a hybrid technique combining abdominal robotic dissection and transanal total mesorectal excision. This procedure was performed in a 50-year-old man with rectal adenocarcinoma at 5 cm from the dentate lane. Preoperative staging was T2N0M0. Surgery went well without complications, and estimated blood loss was less than 50 mL. Robotic surgical time was 90 min, and total operative time was 160 min. The patient was discharged on postoperative day 3...
March 6, 2017: Techniques in Coloproctology
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