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tumor immunological microenvironment

Frederick S Varn, Yue Wang, Chao Cheng
Immune checkpoint inhibitors have shown great potential in treating solid tumors, inducing durable remission and prolonged survival time in responders. Despite their promise, a large fraction of patients remains unresponsive to these treatments highlighting the need for biomarkers that can predict patient sensitivity. Pre-treatment gene expression profiles for patients receiving immune checkpoint inhibitors have recently become available, establishing a new medium by which to discover biomarkers that predict therapy response...
2019: Oncoimmunology
Gijs G Zom, Marian M J H P Willems, Selina Khan, Tetje C van der Sluis, Jan Willem Kleinovink, Marcel G M Camps, Gijsbert A van der Marel, Dmitri V Filippov, Cornelis J M Melief, Ferry Ossendorp
BACKGROUND: Ligands for the Toll-like receptor (TLR) family can induce activation of cells of the innate immune system and are widely studied for their potential to enhance adaptive immunity. Conjugation of TLR2-ligand Pam3CSK4 to synthetic long peptides (SLPs) was shown to strongly enhance the induction of antitumor immunity. To further improve cancer vaccination, we have previously shown that the novel TLR2-L Amplivant (AV), a modified Pam3CSK4, potentiates the maturation effects on murine DCs...
December 12, 2018: Journal for Immunotherapy of Cancer
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
Stefania Oliva, Rossella Troia, Mattia D'Agostino, Mario Boccadoro, Francesca Gay
In the biology of multiple myeloma (MM), immune dysregulation has emerged as a critical component for novel therapeutic strategies. This dysfunction is due to a reduced antigen presentation, a reduced effector cell ability and a loss of reactive T cells against myeloma, together with a bone marrow microenvironment that favors immune escape. The Programmed Death-1 (PD-1) pathway is associated with the regulation of T cell activation and with the apoptotic pathways of effector memory T cells. Specifically, the binding with PD-1 ligand (PD-L1) on the surface of tumor plasma cells down-regulates T cell-proliferation, thus contributing to the immune escape of tumor cells...
2018: Frontiers in Immunology
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
Melanie Boxberg, Lena Leising, Katja Steiger, Moritz Jesinghaus, Aezlat Alkhamas, Marion Mielke, Nicole Pfarr, Carolin Götz, Klaus Dietrich Wolff, Wilko Weichert, Andreas Kolk
Immunotherapy shows promising results and revolutionizes treatment of oral squamous cell carcinoma (OSCC). The immunologic microenvironment might have prognostic/predictive implications. Morphologic immunologic parameters (inflammatory infiltrate, stromal content, and budding activity [BA] [potentially indicating epithelial-mesenchymal transition]) were evaluated in 66 human primary therapy-naive OSCCs. Intraepithelial/stromal tumor-infiltrating lymphocytes (TILs; CD3+ /CD4+ /CD8+ /CD4+ FOXP3+ /IL-17A+ ) were quantified, and ratios were calculated...
December 10, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Gabriele Madonna, Carmen Ballesteros-Merino, Zipei Feng, Carlo Bifulco, Mariaelena Capone, Diana Giannarelli, Domenico Mallardo, Ester Simeone, Antonio M Grimaldi, Corrado Caracò, Gerardo Botti, Bernard A Fox, Paolo A Ascierto
Background : Tumor microenvironment may have a key role in providing immunological markers that can help predict clinical response to treatment with checkpoint inhibitors. We investigated whether the baseline expression of PD-L1 in advanced melanoma patients treated with ipilimumab may correlate with clinical outcome. Methods : PD-L1 expression was assessed in 114 patients with advanced melanoma treated with ipilimumab and, in a cohort of 77 patients, a comprehensive assessment using multispectral imaging to assess the presence and distribution of CD3+, CD8+, CD163+, FOXP3+ and PD-L1+ cells inside and at periphery of the tumor was performed...
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
N Ahmadi, A Ahmadi, E Kheirali, M Hossein Yadegari, M Bayat, A Shajiei, A Ali Amini, S Ashrafi, M Abolhassani, S Faezi, S Amir Yazdanparast, M Mahdavi
OBJECTIVE: The effect of candidemia on immunologic parameters in breast tumor bearing patients is not well studied. Here, we hypothesised that candidemia in the tumor background may change the outcome of immunologic parameters and tumor condition. METHOD: Mice were divided into four groups, including normal, tumor, Candida infected (only Candidiasis) and tumor/Candidiasis groups. Tumor changes were recorded daily after tumor transplantation and induction of candidemia...
November 20, 2018: Journal de Mycologie Médicale
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
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
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
Ryan S Lane, Julia Femel, Alec P Breazeale, Christopher P Loo, Guillaume Thibault, Andy Kaempf, Motomi Mori, Takahiro Tsujikawa, Young Hwan Chang, Amanda W Lund
Mechanisms of immune suppression in peripheral tissues counteract protective immunity to prevent immunopathology and are coopted by tumors for immune evasion. While lymphatic vessels facilitate T cell priming, they also exert immune suppressive effects in lymph nodes at steady-state. Therefore, we hypothesized that peripheral lymphatic vessels acquire suppressive mechanisms to limit local effector CD8+ T cell accumulation in murine skin. We demonstrate that nonhematopoietic PD-L1 is largely expressed by lymphatic and blood endothelial cells and limits CD8+ T cell accumulation in tumor microenvironments...
October 31, 2018: Journal of Experimental Medicine
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