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cancer immunological microenvironment

Bettzy Stephen, Joud Hajjar
Tumor exists as a complex network of structures with an ability to evolve and evade the host immune surveillance mechanism. The immune milieu which includes macrophages, dendritic cells, natural killer cells, neutrophils, mast cells, B cells, and T cells are found in the core, the invasive margin, or the adjacent stromal or lymphoid component of the tumor. The immune infiltrate is heterogeneous and varies within a patient and between patients of the same tumor histology. The location, density, functionality, and the crosstalk between the immune cells in the tumor microenvironment influence the nature of immune response, prognosis, and treatment outcomes in cancer patients...
2018: Advances in Experimental Medicine and Biology
Ru-Jun Mo, Zhao-Dong Han, Ying-Ke Liang, Jian-Heng Ye, Shu-Lin Wu, Sharron X Lin, Yan-Qiong Zhang, Sheng-Da Song, Fu-Neng Jiang, Wei-De Zhong, Chin-Lee Wu
To investigate immune profile consisting of stromal PD-L1 expression, inhibitory or non-T-cell inflamed tumor microenvironment that may predict response to anti-PD-L1/PD-1 immunotherapy in prostate cancer, we validated the specificity of a PD-L1 monoclonal antibody (E1L3N) and identified PD-L1 specific expression in prostatic stromal nerve cells. PD-L1 expression was analyzed in 73 primary prostate cancers and 7 castration-resistant prostate cancers (CRPC) by IHC and resulting data from primary prostate cancers were correlated with tumor-associated lymphocytes (TALs), clinicopathological characteristics and clinical outcome...
December 11, 2018: International Journal of Cancer. Journal International du Cancer
Jean-Philippe Foy, Chloé Bertolus, Sandra Ortiz-Cuaran, Marie-Alexandra Albaret, William N Williams, Wenhua Lang, Solène Destandau, Geneviève De Souza, Emilie Sohier, Janice Kielbassa, Emilie Thomas, Sophie Deneuve, Patrick Goudot, Alain Puisieux, Alain Viari, Li Mao, Christophe Caux, S M Lippman, P Saintigny
Oral squamous cell carcinoma (OSCC) is a major cause of cancer-associated morbidity and mortality and may develop from oral premalignant lesions (OPL). An improved molecular classification of OPL may help refining prevention strategies. We identified two main OPL gene-expression subtypes, named immunological and classical, in 86 OPL (discovery dataset). A gene expression-based score was then developed to classify OPL samples from three independent datasets, including 17 (GSE30784),13 (GSE10174) and 15 (GSE85195) OPLs, into either one of the two gene-expression subtypes...
2018: Oncoimmunology
Soizic Garaud, Pawel Zayakin, Laurence Buisseret, Undine Rulle, Karina Silina, Alexandre de Wind, Gert Van den Eyden, Denis Larsimont, Karen Willard-Gallo, Aija Linē
An important role for tumor infiltrating B lymphocytes (TIL-B) in the immune response to cancer is emerging; however, very little is known about the antigen specificity of antibodies produced in situ . The presence of IgA antibodies in the tumor microenvironment has been noted although their biological functions and clinical significance are unknown. This study used a 91-antigen microarray to examine the IgG and IgA autoantibody repertoires in breast cancer (BC). Tumor and adjacent breast tissue supernatants and plasma from BC patients together with normal breast tissue supernatants and plasma from healthy controls (patients undergoing mammary reduction and healthy blood donors) were analyzed to investigate relationships between autoantibodies and the clinical, histological and immunological features of tumors...
2018: Frontiers in Immunology
Timothy E Krueger, Daniel L J Thorek, Alan K Meeker, John T Isaacs, W Nathaniel Brennen
BACKGROUND: Prostate cancer is characterized by T-cell exclusion, which is consistent with their poor responses to immunotherapy. In addition, T-cells restricted to the adjacent stroma and benign areas are characterized by anergic and immunosuppressive phenotypes. In order for immunotherapies to produce robust anti-tumor responses in prostate cancer, this exclusion barrier and immunosuppressive microenvironment must first be overcome. We have previously identified mesenchymal stem cells (MSCs) in primary and metastatic human prostate cancer tissue...
November 28, 2018: Prostate
Guopei Luo, Na Liu
In the integrative theory, chronic irritations induce tumors with genetic alterations and rapid proliferative ability. Tumor cells reprogram the metabolism and employ aerobic glycolysis to sustain rapid growth. The host provides both the nutrients and exhaust system to support tumor growth via the tumor microenvironment. Under certain conditions, such as aging, diabetes, obesity and a high‑fat diet, the exhaust system is impaired, triggering a metabolic imbalance between the tumor and host. This is similar to a problematic car with an advanced motor with an out‑of‑date exhaust system...
November 28, 2018: International Journal of Molecular Medicine
Yun Liang, Weiguo Lü, Xiaofei Zhang, Bingjian Lü
BACKGROUND: Neoadjuvant chemotherapy (NACT) has been recently accepted as an effective alternative in patients with locally advanced cervical cancer. However, little is known about the effects of NACT on the immunological microenvironment in cervical cancers. In this study, we analyzed the alterations of tumor infiltrating lymphocytes (TILs) before and after NACT and analyzed their prognostic significance in advanced cervical cancer patients treated with platinum-based NACT. METHODS: We recruited 137 patients with stage Ib2 and IIa2 cervical cancer retrospectively...
November 24, 2018: Diagnostic Pathology
Dirk Zboralski, Anna Frömming
Clinically apparent tumors have often established an immunosuppressive tumor microenvironment which renders them "cold," meaning that there are low numbers of immune cells within the tumor. Consequently, novel immunotherapy approaches such as checkpoint inhibitors fail to reactivate the tumor-targeted immune cells. Here we describe the generation of heterotypic tumor-stroma spheroids to study various approaches aiming at the reactivation of cancer immunosurveillance. These spheroids allow to investigate whether a certain immunotherapy or a combination treatment is able to stimulate antitumor immunity in poorly immunological ("cold") tumors, by increasing the number of tumor-infiltrating immune cells ("hot" tumors)...
2019: Methods in Molecular Biology
Pil Soo Sung, Jeong Won Jang
Hepatocellular carcinoma (HCC) is currently the third leading cause of malignancy-related mortalities worldwide. Natural killer (NK) cells are involved in the critical role of first line immunological defense against cancer development. Defects in NK cell functions are recognized as important mechanisms for immune evasion of tumor cells. NK cell function appears to be attenuated in HCC, and many previous reports suggested that NK cells play a critical role in controlling HCC, suggesting that boosting the activity of dysfunctional NK cells can enhance tumor cell killing...
November 19, 2018: International Journal of Molecular Sciences
Felix Sim, Rom Leidner, Richard Bryan Bell
The immune system has a vital role in the development, establishment, and progression of head and neck squamous cell carcinoma (HNSCC). Immune evasion of cancer cells leads to progression of HNSCC. An understanding of this mechanism provides the basis for improved therapies and outcomes for patients. Through the tumor's influence on the microenvironment, the immune system can be exploited to promote metastasis, angiogenesis, and growth. This article provides an overview of the interaction between immune infiltrating cells in the tumor microenvironment, and the immunologic principles related to HNSCC...
February 2019: Oral and Maxillofacial Surgery Clinics of North America
Lifei Xie, Yang Yang, Jie Meng, Tao Wen, Jian Liu, Haiyan Xu
Macrophages are predominant immune cells in the tumor microenvironment where they display an immunosuppressive M2 phenotype to support tumor growth. Reprogramming M2-like tumor-associated macrophages (TAMs) to antitumor M1 phenotype represents as a promising strategy in cancer immunotherapy. In this work we reported that one cationic polysaccharide spermine modified pullulan (PS) could act as an effective immunological stimulator to modulating either naïve (M0) or M2 macrophages towards M1 phenotype. We showed that PS upregulated the expression of TLR1/3/4 and promoted the phosphorylation of Akt, Erk, JNK, following the activation of NF-κB, which led to the polarization towards M1...
November 13, 2018: International Journal of Biological Macromolecules
Prasenjit Chakraborty, Tanusri Karmakar, Neeraj Arora, Geetashree Mukherjee
Head and neck squamous cell carcinoma (HNSCC) is responsible for a large number of deaths each year. Oral cancer is the most frequent subtype of HNSCC. Historically, oral cancer has been associated with an increase in the consumption of tobacco and alcohol products, seen especially in the Asian subcontinent. It has also been associated with infection by the human papilloma virus (HPV), particularly strain HPV16. Treatment usually involves a multidisciplinary approach of surgery combined with chemotherapy and radiation...
October 2018: Heliyon
Molly A Ingersoll, Xue Li, Brant A Inman, John W Greiner, Peter C Black, Rosalyn M Adam
The Fourth Annual Albert Institute Bladder Cancer Care and Research Symposium was held from September 14th-16th in Houston, Texas. The symposium covered a range of topics relevant to bladder cancer, including basic science aspects of immunology and immunotherapy that inform clinical management; intravesical therapy for non-muscle invasive disease; understanding the nuances of carcinoma in situ ; and optimizing patient care and outcomes following therapy. The moving landscape of bladder cancer from an industry perspective was also discussed...
October 29, 2018: Bladder Cancer
S Kareemaghay, M Tavassoli
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, accounting for more than 550,000 cases and 380,000 deaths annually. The primary risk factors associated with HNSCC are tobacco use and alcohol consumption; nevertheless genetic predisposition and oncogenic viruses also play important roles in the development of these malignancies. The current treatments for HNSCC patients include surgery, chemotherapy, radiotherapy, and cetuximab, and combinations of these. However, these treatments are associated with significant toxicity, and many patients are either refractory to the treatment or relapse after a short period...
November 3, 2018: International Journal of Oral and Maxillofacial Surgery
Ryota Kondou, Akira Iizuka, Chizu Nonomura, Haruo Miyata, Tadashi Ashizawa, Takeshi Nagashima, Keiichi Ohshima, Kenichi Urakami, Masatoshi Kusuhara, Ken Yamaguchi, Yasuto Akiyama
In 2014, the Shizuoka Cancer Center launched project High‑tech Omics‑based Patient Evaluation (HOPE), which features whole exome sequencing (WES) and gene expression profiling (GEP) of fresh surgical specimens from cancer patients. With the development of clinical trials of programmed death‑1 (PD‑1)/PD‑ligand 1 (PD‑L1) blockade, PD‑L1 expression and a high tumor mutation burden become possible biomarkers that could be used to predict immune responses. In this study, based on WES and GEP data from 1,734 tumors from the HOPE project, we established a tumor microenvironment (TME) immune‑type classification consisting of 4 types to evaluate the immunological status of cancer patients and analyze immunological pathways specific for immune types...
November 2, 2018: International Journal of Oncology
Wenting Du, Huocong Huang, Noah Sorrelle, Rolf A Brekken
Immune checkpoint blockade has achieved significant therapeutic success for a subset of cancer patients; however, a large portion of cancer patients do not respond. Unresponsive tumors are characterized as being immunologically "cold," indicating that these tumors lack tumor antigen-specific primed cytotoxic T cells. Sitravatinib is a spectrum-selective tyrosine kinase inhibitor targeting TAM (TYRO3, AXL, MerTK) and split tyrosine-kinase domain-containing receptors (VEGFR and PDGFR families and KIT) plus RET and MET, targets that contribute to the immunosuppressive tumor microenvironment...
November 2, 2018: JCI Insight
Charles G Drake, Mark N Stein
Although kidney cancer (renal cell carcinoma [RCC]) is susceptible to immunotherapy, the immunologic aspects of the tumor microenvironment (TME) in RCC are relatively unique among tumor types. In RCC, baseline CD8 T-cell infiltration is associated with a worse prognosis. In addition, kidney cancer responds to programmed death-1/programmed death-ligand 1 blockade, despite a relatively low tumor mutation burden. Recent clinical data highlight the efficacy of combined immune checkpoint blockade and demonstrate that combining antiangiogenic agents with programmed death-1/programmed death-ligand 1 blockade has additive activity...
October 29, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Dan P Zandberg, Robert L Ferris
In head and neck cancer, we continue to work towards a more personalized approach to treatment of patients, where analysis of a patient's tumor guides targeting of molecular or immunologic pathways. Critically important to this pursuit is a better understanding of the direct biologic effect of a drug or combination on the tumor microenvironment in humans, as well as biomarker discovery. These goals are consistent with the primary purpose of a "window of opportunity" trial and while conduct of these trials requires a careful balance of benefits and potential risks, to date these trials have been both feasible and safe in HNSCC in the curative intent setting...
October 27, 2018: Current Treatment Options in Oncology
Yusheng Lu, Shu Lian, Yuying Ye, Ting Yu, Haiyan Liang, Yunlong Cheng, Jingjing Xie, Yewei Zhu, Xiaodong Xie, Suhong Yu, Yu Gao, Lee Jia
A perfect microenvironment facilitates the activated circulating tumor cells (CTCs) to spark the adhesion-invasion-extravasation metastatic cascade in their premetastatic niche. Platelet-CTC interaction contributes to the progression of tumor malignancy by protecting CTCs from shear stress and immunological assault, aiding CTCs entrapment in the capillary bed, enabling CTCs to successfully exit the bloodstream and enter the tissue, inducing epithelial-mesenchymal-like transition (EMT), and assisting in the establishment of metastatic foci...
October 23, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Angela M Magnuson, Evgeny Kiner, Ayla Ergun, Jun Seok Park, Natasha Asinovski, Adriana Ortiz-Lopez, Aoife Kilcoyne, Elisa Paoluzzi-Tomada, Ralph Weissleder, Diane Mathis, Christophe Benoist
FoxP3+ T regulatory (Treg) cells are central elements of immunologic tolerance. They are abundant in many tumors, where they restrict potentially favorable antitumor responses. We used a three-pronged strategy to identify genes related to the presence and function of Tregs in the tumor microenvironment. Gene expression profiles were generated from tumor-infiltrating Tregs (TITRs) of both human and mouse tumors and were compared with those of Tregs of lymphoid organs or normal tissues from the same individuals...
November 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
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