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tumor infiltrating lymphocytes

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https://www.readbyqxmd.com/read/28096371/cox2-mpges1-pge2-pathway-regulates-pd-l1-expression-in-tumor-associated-macrophages-and-myeloid-derived-suppressor-cells
#1
Victor Prima, Lyudmila N Kaliberova, Sergey Kaliberov, David T Curiel, Sergei Kusmartsev
In recent years, it has been established that programmed cell death protein ligand 1 (PD-L1)-mediated inhibition of activated PD-1(+) T lymphocytes plays a major role in tumor escape from immune system during cancer progression. Lately, the anti-PD-L1 and -PD-1 immune therapies have become an important tool for treatment of advanced human cancers, including bladder cancer. However, the underlying mechanisms of PD-L1 expression in cancer are not fully understood. We found that coculture of murine bone marrow cells with bladder tumor cells promoted strong expression of PD-L1 in bone marrow-derived myeloid cells...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28093487/a-pilot-trial-of-the-combination-of-vemurafenib-with-adoptive-cell-therapy-in-patients-with-metastatic-melanoma
#2
Drew C Deniger, Mei Li M Kwong, Anna Pasetto, Mark E Dudley, John R Wunderlich, Michelle M Langhan, Chyi-Chia Richard Lee, Steven A Rosenberg
PURPOSE: This pilot feasibility clinical trial evaluated the coadministration of vemurafenib, a small-molecule antagonist of BRAF(V600) mutations, and tumor-infiltrating lymphocytes (TIL) for the treatment of metastatic melanoma. EXPERIMENTAL DESIGN: A metastatic tumor was resected for growth of TILs, and patients were treated with vemurafenib for 2 weeks, followed by resection of a second lesion. Patients then received a nonmyeloablative preconditioning regimen, infusion of autologous TILs, and high-dose interleukin-2 administration...
January 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28093446/tumor-infiltrating-merkel-cell-polyomavirus-specific-t-cells-are-diverse-and-associated-with-improved-patient-survival
#3
Natalie J Miller, Candice D Church, Lichun Dong, David Crispin, Matthew P Fitzgibbon, Kristina Lachance, Lichen Jing, Michi Shinohara, Ioannis Gavvovidis, Gerald Willimsky, Martin McIntosh, Thomas Blankenstein, David M Koelle, Paul Nghiem
Tumor-infiltrating CD8(+) T cells are associated with improved survival of patients with Merkel cell carcinoma (MCC), an aggressive skin cancer causally linked to Merkel cell polyomavirus (MCPyV). However, CD8(+) T-cell infiltration is robust in only 4% to 18% of MCC tumors. We characterized the T-cell receptor (TCR) repertoire restricted to one prominent epitope of MCPyV (KLLEIAPNC, "KLL") and assessed whether TCR diversity, tumor infiltration, or T-cell avidity correlated with clinical outcome. HLA-A*02:01/KLL tetramer(+) CD8(+) T cells from MCC patient peripheral blood mononuclear cells (PBMC) and tumor-infiltrating lymphocytes (TIL) were isolated via flow cytometry...
January 16, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28088700/chlorogenic-acid-ameliorated-concanavalin-a-induced-hepatitis-by-suppression-of-toll-like-receptor-4-signaling-in-mice
#4
Yinglin Yuan, Xia Gong, Li Zhang, Rong Jiang, Junxia Yang, Bin Wang, Jingyuan Wan
Chlorogenic acid (CGA), one of the most abundant dietary polyphenolic compounds, has been reported to exhibit anti-inflammatory ability. However, the hepatoprotective effects and molecular mechanisms of CGA on concanavalin A (Con A)-induced hepatitis have not been explored. In the present study, we found that pretreatment with CGA dose-dependently inhibited the elevation of plasma aminotransferases and alleviated hepatic pathological damage as well as hepatocyte apoptosis in Con A-exposed mice. Additionally, CGA markedly suppressed the production of serum tumor necrosis factor (TNF)-α and interferon (IFN)-γ, alleviated the infiltration of hepatic macrophages, neutrophils, and activated CD4(+) T lymphocytes in Con A-primed mice...
January 12, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28075442/increased-expression-of-pd%C3%A2-l1-by-the-human-papillomavirus-16-e7-oncoprotein-inhibits-anticancer-immunity
#5
Chaoqi Liu, Jiao Lu, Huiqun Tian, Wei Du, Lin Zhao, Jing Feng, Ding Yuan, Zhiying Li
Cytotoxic T lymphocyte dysfunction is frequently associated with PD‑L1/PD‑1 pathway activation, and is a principal obstacle in cancer therapy. In the present study, the mechanisms underlying the human papillomavirus (HPV)‑induced evasion of cervical cancer cells to the host immune system via the programmed death ligand  1/programmed death 1 (PD‑L1/PD‑1) signaling pathway was investigated. A significant increase in the expression of the HPV16E7 viral protein and PD‑L1 in cervical tissues was observed when compared with normal cervical tissues...
January 5, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28074226/synergistic-effects-of-host-b7-h4-deficiency-and-gemcitabine-treatment-on-tumor-regression-and-anti-tumor-t-cell-immunity-in-a-mouse-model
#6
Joanne Leung, Philippe St-Onge, John Stagg, Woong-Kyung Suh
B7-H4 (B7x/B7S1), a B7 family inhibitor of T cell activity, is expressed in multiple human cancers and correlates with decreased infiltrating lymphocytes and poor prognosis. In murine models, tumor-expressed B7-H4 enhances tumor growth and reduces T cell immunity, and blockade of tumor-B7-H4 rescues T cell activity and lowers tumor burden. This implicates B7-H4 as a target for cancer immunotherapy, yet limits the efficacy of B7-H4 blockade exclusively to patients with B7-H4+ tumors. Given the expression of B7-H4 on host immune cells, we have previously shown that BALB/c mice lacking host B7-H4 have enhanced anti-tumor profiles, yet similar 4T1 tumor growth relative to control...
January 10, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28073775/dasatinib-changes-immune-cell-profiles-concomitant-with-reduced-tumor-growth-in-several-murine-solid-tumor-models
#7
Can Hekim, Mette Ilander, Jun Yan, Erin Michaud, Richard Smykla, Markus Vähä-Koskela, Paula Savola, Siri Tähtinen, Leena Saikko, Akseli Hemminki, Panu E Kovanen, Kimmo Porkka, Francis Yf Lee, Satu Mustjoki
Dasatinib, a broad range tyrosine kinase inhibitor (TKI), induces rapid mobilization of lymphocytes and clonal expansion of cytotoxic cells in leukemia patients. Here, we investigated whether dasatinib could induce beneficial immunomodulatory effects in solid tumor models. The effects on tumor growth and on the immune system were studied in four different syngeneic mouse models (B16.OVA melanoma, 1956 sarcoma, MC38 colon, and 4T1 breast carcinoma). Both peripheral blood (PB) and tumor samples were immunophenotyped during treatment...
January 10, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28073773/long-term-survival-and-clinical-benefit-from-adoptive-t-cell-transfer-in-stage-iv-melanoma-patients-is-determined-by-a-four-parameter-tumor-immune-signature
#8
Sara M Melief, Valeria V Visconti, Marten Visser, Merel van Diepen, Ellen H W Kapiteijn, Joost H van den Berg, John B A G Haanen, Vincent T H B M Smit, Jan Oosting, Sjoerd H van der Burg, Els M E Verdegaal
The presence of tumor-infiltrating immune cells is associated with longer survival and a better response to immunotherapy in early-stage melanoma, but a comprehensive study of the in situ immune microenvironment in stage IV melanoma has not been performed. We investigated the combined influence of a series of immune factors on survival and response to adoptive cell transfer (ACT) in stage IV melanoma patients. Metastases of 73 stage IV melanoma patients, 17 of which were treated with ACT, were studied with respect to the number and functional phenotype of lymphocytes and myeloid cells as well as for expression of galectins-1, -3, and -9...
January 10, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28072971/-expression-of-pd-1-pd-l1-in-triple-negative-breast-carcinoma-and-its-significance
#9
W Zhang, G X Xu, J J Li, X Liu, Y J Chen, F Zhang
Objective: To investigate the correlation between the expression of PD-1, PD-L1 and clinicopathologic parameters in triple negative breast carcinoma (TNBC). Methods: Samples from 151 patients with TNBC and 65 cases of other breast carcinomas (non-TNBC) were examined for PD-L1 and PD-1 expression by immunohistochemical staining on tissue microarray. Results: The expression of PD-L1 and PD-1 in the tumor cells and interstitial lymphocytes in TNBC was significantly (P<0.05)higher than that in non-TNBC.In TNBC, the expression rates of PD-L1 in the cancer nests and stroma were 16...
January 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28060552/the-root-extract-of-gentiana-macrophylla-pall-alleviates-b19-ns1-exacerbated-liver-injuries-in-nzb-w-f1-mice
#10
Ming-Jen Sheu, Chun-Ching Chiu, Deng-Jye Yang, Tsai-Ching Hsu, Bor-Show Tzang
The nonstructural protein NS1 of human parvovirus B19 (B19) is known to exacerbate disease activity in systemic lupus erythematosus (SLE). However, no specific medicine for B19 infection is available. The roots of Gentiana macrophylla Pall. (GM), the traditional Chinese medicine "Qinjiao," have been used for centuries to treat rheumatic disease, including SLE. Herein, we aimed to investigate the effects of GM root extract (100 and 300 mg/kg body weight) on B19-NS1-exacerbated liver injury in NZB/W F1 mice; liver tissues were assessed by hematoxylin-eosin staining and immunoblotting...
January 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28058667/evaluation-of-high-risk-features-of-primary-enucleation-of-patients-with-retinoblastoma-in-a-tertiary-center-of-a-developing-country-in-the-era-of-intra-arterial-chemotherapy
#11
Funda Dikkaya, Ahmet Murat Sarıcı, Firuze Erbek, Tiraje Celkan, Mehmet Serhat Mangan, Övgü Aydın, Cuyan Demirkesen, Halit Pazarlı
PURPOSE: To evaluate the frequency of high-risk histopathologic factors in Turkish children enucleated for retinoblastoma and to analyze the association between growth pattern, rosetta formation, tumor thickness, presence of necrosis, calcification, neovascularization, rate of mitosis, and high-risk histopathologic factors. METHODS: Pathology reports of 59 eyes who had received enucleation for retinoblastoma were reviewed retrospectively. The histopathologic data included presence of choroidal invasion, optic nerve invasion, scleral extension, tumor thickness, presence of necrosis, calcification, neovascularization, rosetta formation and lymphocyte infiltration, rate of mitosis, and growth pattern...
January 5, 2017: International Ophthalmology
https://www.readbyqxmd.com/read/28058578/pd-l1-expression-and-tumor-infiltrating-pd-1-%C3%A2-lymphocytes-associated-with-outcome-in-her2-%C3%A2-breast-cancer-patients
#12
Julia Y S Tsang, Wai-Ling Au, Kwan-Yin Lo, Yun-Bi Ni, Thazin Hlaing, Jintao Hu, Siu-Ki Chan, Kui-Fat Chan, Sai-Yin Cheung, Gary M Tse
PURPOSE: Clinical trials showing programmed death (PD)-1-PD-ligand 1 (L1) axis as a promising therapeutic target in melanoma and non-small cell lung cancers have made the pathway a focus of recent attention. However, the data regarding PD-L1/PD-1 in breast cancer are inconsistent. Given the heterogeneity of breast cancers, the clinical relevance of PD-L1 and PD-1 tumor infiltrating lymphocytes (TIL) may vary according to subtypes of breast cancer. We aim to investigate PD-L1 expression in a large cohort of breast cancers and analyze its clinico-pathological as well as outcome relationship according to molecular subtypes...
January 5, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28057182/auto-immunit%C3%A3-et-gestion-des-toxicit%C3%A3-s-des-traitements-par-anti-check-point-inhibiteurs
#13
Marie Senant, Delphine Giusti, Laurence Weiss, Marie-Agnès Dragon-Durey
AUTOIMMUNITY AND MANAGEMENT OF THE IMMUNE-RELATED ADVERSE EFFECTS OF THE IMMUNE CHECKPOINT INHIBITORS: The immune checkpoint molecules such as CTLA-4 and PD-1 are involved in the tolerance mechanisms preventing the immune system to react against the self-antigens. When these receptors expressed on the lymphocyte membrane, bind to their ligands, they induce a negative signal to the cell which becomes unable to be completely activated in the presence of its antigen. In a context of tumor, the infiltrating T cells are frequently exhausted due to the expression of CTLA-4 and PD-1 ligands by the microenvironment impairing the antitumoral immunity...
November 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/28057179/biomarqueurs-pr%C3%A3-dictifs-de-r%C3%A3-ponse-aux-traitements-bloquant-les-voies-de-costimulation-inhibitrices
#14
Franck Pagès, Clémence Granier, Amos Kirilovsky, Carine Elsissy, Eric Tartour
Immunotherapies targeting co-inhibitory receptors recently open a new promising approach of cancer treatment. Indeed, an objective clinical response was observed after treatment by anti-CTLA-4 and anti-PD-1 in many indications but the treatment still failed in 70 to 80 % of cases treated. Given the adverse effects and the high cost of these therapies, there is a need for the development of biomarkers. This review focus on potential predictive biomarkers. In peripheral blood, high level of Il-2 soluble receptor at baseline and absence of ICOS+ CD4-T lymphocytes induction may be associated with the absence of clinical response for melanoma patients treated by ipilimumab (anti-CTLA-4)...
November 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/28052400/programmed-death-1-ligand-1-and-2-expression-in-cutaneous-squamous-cell-carcinoma-and-their-relationship-with-tumor-infiltrating-dendritic-cells
#15
Qingqing Jiao, Cuiping Liu, Wenzhong Li, Wei Li, Fuming Fang, Qihong Qian, Xueguang Zhang
The Programmed Death-1 (PD-1) receptor ligands, PD-L1 and PD-L2, are costimulatory molecules that contribute to the negative regulation of T-lymphocyte activation. It is still unclear whether there is correlation between PD-L1 or PD-L2 and tumor infiltrating dendritic cells (TIDCs) in cutaneous squamous cell carcinoma (CSCC). The aim of this study was to analyze PD-L1 and PD-L2 expression and dendritic cells (DCs) infiltration in tumor tissue of CSCC patients and investigate their clinical significance. Immunohistochemical analysis was used to evaluate the expression of PD-L1, PD-L2, CD1a, and CD83 in 61 CSCC tissues...
January 3, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28052254/pan-cancer-immunogenomic-analyses-reveal-genotype-immunophenotype-relationships-and-predictors-of-response-to-checkpoint-blockade
#16
Pornpimol Charoentong, Francesca Finotello, Mihaela Angelova, Clemens Mayer, Mirjana Efremova, Dietmar Rieder, Hubert Hackl, Zlatko Trajanoski
The Cancer Genome Atlas revealed the genomic landscapes of human cancers. In parallel, immunotherapy is transforming the treatment of advanced cancers. Unfortunately, the majority of patients do not respond to immunotherapy, making the identification of predictive markers and the mechanisms of resistance an area of intense research. To increase our understanding of tumor-immune cell interactions, we characterized the intratumoral immune landscapes and the cancer antigenomes from 20 solid cancers and created The Cancer Immunome Atlas (https://tcia...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28052005/bortezomib-augments-lymphocyte-stimulatory-cytokine-signaling-in-the-tumor-microenvironment-to-sustain-cd8-t-cell-antitumor-function
#17
Samuel T Pellom, Duafalia F Dudimah, Menaka C Thounaojam, Roman V Uzhachenko, Ashutosh Singhal, Ann Richmond, Anil Shanker
Tumor-induced immune tolerance poses a major challenge for therapeutic interventions aimed to manage cancer. We explored approaches to overcome T-cell suppression in murine breast and kidney adenocarcinomas, and lung fibrosarcoma expressing immunogenic antigens. We observed that treatment with a reversible proteasome inhibitor bortezomib (1 mg/kg body weight) in tumor-bearing mice significantly enhanced the expression of lymphocyte-stimulatory cytokines IL-2, IL-12, and IL-15. Notably, bortezomib administration reduced pulmonary nodules of mammary adenocarcinoma 4T1...
December 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/28051835/mesothelioma-and-interferon-%C3%AE-dependent-chemokine-ip-10
#18
P Fallahi, F Ragusa
Recently it has been shown that interferon (IFN)-γ plays an important role in mesothelioma, mediated by the main IFN-γ dependent chemokines, chemokine (C-X-C motif) ligand (CXCL)10/IFN-γ- induced protein 10 (IP-10). IP-10 is up-regulated in malignant mesothelioma (MM), suggesting a relationship with development of these tumors. Nanoparticles containing nickel, that increase the risk for pleural diseases, induced increased levels of IP-10 in rat pleural mesothelial cells. Chemokine (C-X-C motif) receptor (CXCR)3 expression in CD4(+) T cells from pleural plaques and MMs was significantly decreased compared with that from healthy donors suggesting that CXCR3, IFN-γ, and IP-10 may be candidates to detect and monitor disease status...
November 2016: La Clinica Terapeutica
https://www.readbyqxmd.com/read/28045912/claudin-low-breast-cancer-clinical-pathological-characteristics
#19
Kay Dias, Anna Dvorkin-Gheva, Robin M Hallett, Ying Wu, John Hassell, Gregory R Pond, Mark Levine, Tim Whelan, Anita L Bane
Claudin-low breast cancer is a molecular type of breast cancer originally identified by gene expression profiling and reportedly associated with poor survival. Claudin-low tumors have been recognised to preferentially display a triple-negative phenotype, however only a minority of triple-negative breast cancers are claudin-low. We sought to identify an immunohistochemical profile for claudin-low tumors that could facilitate their identification in formalin fixed paraffin embedded tumor material. First, an in silico collection of ~1600 human breast cancer expression profiles was assembled and all claudin-low tumors identified...
2017: PloS One
https://www.readbyqxmd.com/read/28043482/immune-response-after-radiofrequency-ablation-and-surgical-resection-in-nonsmall-cell-lung-cancer
#20
Thomas Schneider, Hans Hoffmann, Hendrik Dienemann, Ester Herpel, Claus Peter Heussel, Alexander H Enk, Sabine Ring, Karsten Mahnke
The objective includes radiofrequency ablation (RFA) of a cancerous nodule results in immunogenic cell death. Tumor antigens are presented and the inflammatory environment may help stimulate adaptive and innate antitumor immunity. The objective of this study was to investigate the immune response following RFA and subsequent surgical resection in early stage non-small cell lung cancer (NSCLC). In methods, a single-session approach of computed tomography-guided tumor biopsy with immediate frozen section (and proof of NSCLC) was performed followed by RFA of the tumor in 4 patients with a solitary pulmonary nodule...
July 2016: Seminars in Thoracic and Cardiovascular Surgery
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