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tumor infiltrating t lymphocyte

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https://www.readbyqxmd.com/read/28741900/the-avidity-of-tumor-specific-t-cells-amplified-by-a-pdc-based-assay-can-predict-the-clinical-evolution-of-melanoma-patients
#1
Julie Charles, Laurence Chaperot, Bruno Revol, Marine Baudin, Stephane Mouret, Agnes Hamon, Marie-Therese Leccia, Joel Plumas, Caroline Aspord
The advent of immune-checkpoint blockers and targeted therapies has changed the outcome of melanoma. However, many patients experience relapses, emphasizing the need for predictive and prognostic biomarkers. We developed a strategy based on plasmacytoid dendritic cells (pDCs) loaded with melanoma-tumor antigens that allows eliciting highly efficient antitumor T-cell responses. We used it to investigate antitumor T-cell functionality in peripheral blood mononuclear cells and tumor-infiltrating lymphocytes from melanoma patients...
July 25, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28739701/the-prognostic-significance-of-the-tumor-infiltrating-programmed-cell-death-1-to-cd8-lymphocyte-ratio-in-patients-with-colorectal-cancer
#2
Masatsune Shibutani, Kiyoshi Maeda, Hisashi Nagahara, Tatsunari Fukuoka, Shigetomi Nakao, Shinji Matsutani, Kosei Hirakawa, Masaichi Ohira
BACKGROUND/AIM: Tumor-infiltrating lymphocytes (TILs) have been reported to reflect the antitumor immunity of the host and correlate with the therapeutic outcomes and survival. Nowadays TILs are attracting attention as new biomarkers of diseases such as colorectal cancer. TILs are classified into several subsets, among which CD8(+) T cells directly attack cancer cells and play a central role in antitumor immunity. A high density of CD8(+) TILs has been reported to correlate with a better clinical outcome...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28737763/melanoma-subtypes-demonstrate-distinct-pd-l1-expression-profiles
#3
Genevieve J Kaunitz, Tricia R Cottrell, Mohammed Lilo, Valliammai Muthappan, Jessica Esandrio, Sneha Berry, Haiying Xu, Aleksandra Ogurtsova, Robert A Anders, Alexander H Fischer, Stefan Kraft, Meg R Gerstenblith, Cheryl L Thompson, Kord Honda, Jonathan D Cuda, Charles G Eberhart, James T Handa, Evan J Lipson, Janis M Taube
PD-L1 expression in the tumor immune microenvironment is recognized as both a prognostic and predictive biomarker in patients with cutaneous melanoma, a finding closely related to its adaptive (IFN-γ-mediated) mechanism of expression. Approximately 35% of cutaneous melanomas express PD-L1, however, the expression patterns, levels, and prevalence in rarer melanoma subtypes are not well described. We performed immunohistochemistry for PD-L1 and CD8 on 200 formalin-fixed paraffin-embedded specimens from patients with acral (n=16), mucosal (n=36), uveal (n=103), and chronic sun-damaged (CSD) (n=45) melanomas (24 lentigo maligna, 13 'mixed' desmoplastic, and 8 'pure' desmoplastic melanomas)...
July 24, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28736431/combined-blockade-of-t-cell-immunoglobulin-and-mucin-domain-3-and-carcinoembryonic-antigen-related-cell-adhesion-molecule-1-results-in-durable-therapeutic-efficacy-in-mice-with-intracranial-gliomas
#4
Jinhu Li, Xiaodong Liu, Yijun Duan, Yueting Liu, Hongqin Wang, Shizhong Lian, Guotao Zhuang, Yimin Fan
BACKGROUND Glioblastoma multiforme (GBM) evades immune surveillance by inducing immunosuppression via receptor-ligand interactions between immune checkpoint molecules. T cell immunoglobulin and mucin domain 3 (Tim-3) is a key checkpoint receptor responsible for exhaustion and dysfunction of T cells and plays a critical role in immunosuppression. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) has been recently identified as a heterophilic ligand for Tim-3. MATERIAL AND METHODS We established an intracranial GBM model using C57BL/6 mice and GL261 cells, and treated the mice with single or combined monoclonal antibodies (mAbs) against Tim-3/CEACAM1...
July 24, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28733541/a-validated-transitional-and-translational-porcine-model-of-hepatocellular-carcinoma
#5
Kyle M Schachtschneider, Regina M Schwind, Kwame A Darfour-Oduro, Arun K De, Lauretta A Rund, Kuldeep Singh, Daniel R Principe, Grace Guzman, Charles E Ray, Howard Ozer, Ron C Gaba, Lawrence B Schook
Difficult questions are confronting clinicians attempting to improve hepatocellular carcinoma (HCC) outcomes. A large animal model with genetic, anatomical, and physiological similarities to humans is required to transition from mouse models to human clinical trials to address unmet clinical needs. To validate our previously reported inducible porcine cancer model (Oncopig) as a transitional HCC model, Oncopig hepatocyte cultures were transformed using Cre recombinase. The resulting porcine HCC cells (pHCC) expressed oncogenic TP53R167H and KRASG12D, and displayed nuclear pleomorphisms with pale to granular cytoplasm arranged in expanded plates similar to human HCC histopathology...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733349/constitutive-ido1-expression-in-human-tumors-is-driven-by-cyclooxygenase-2-and-mediates-intrinsic-immune-resistance
#6
Marc Hennequart, Luc Pilotte, Stefania Cane, Delia Hoffmann, Vincent Stroobant, Etienne De Plaen, Benoît J Van den Eynde
Tumors use various mechanisms to avoid immune destruction. Cyclooxygenase-2 (COX-2) expression may be a driver of immune suppression in melanoma, but the mechanisms involved remain elusive. Here, we show that COX-2 expression drives constitutive expression of indoleamine 2,3-dioxygenase 1 (IDO1) in human tumor cells. IDO1 is an immunosuppressive enzyme that degrades tryptophan. In a series of seven human tumor lines, constitutive IDO1 expression depends on COX-2 and prostaglandin E2 (PGE2), which, upon autocrine signaling through the EP receptor, activates IDO1 via the PKC and PI3K pathways...
July 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28731046/pd-l1-expression-and-the-immune-microenvironment-in-primary-invasive-lobular-carcinomas-of-the-breast
#7
Elizabeth D Thompson, Janis M Taube, Rebecca J Asch-Kendrick, Aleksandra Ogurtsova, Haiying Xu, Rajni Sharma, Alan Meeker, Pedram Argani, Leisha A Emens, Ashley Cimino-Mathews
Tumor-infiltrating lymphocytes and immune checkpoint proteins such as PD-L1 are potential prognostic factors and therapeutic targets in breast cancer. Most studies characterizing the breast tumor immune microenvironment have focused on ductal carcinomas. Here we investigate the tumor microenvironment of primary invasive lobular carcinomas. Previously constructed tissue microarrays of 47 lobular carcinomas were labeled by immunohistochemistry for PD-L1, CD8, CD20, and FoxP3. The stromal immune infiltrate density was qualitatively scored as a percentage of tumor area: 1+ (<5%); 2+ (5-10%); 3+ (10-15%); or 4+ (>50%)...
July 21, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28730761/tumor-infiltrating-lymphocytes-as-a-prognostic-factor-in-malignant-melanoma-review-of-the-literature
#8
Vlad A Gata, Cosmin I Lisencu, Catalin I Vlad, Doina Piciu, Alexandru Irimie, Patriciu Achimas-Cadariu
Malignant melanoma represents the major cause of mortality among skin cancers, with increasing incidence and mortality rates worldwide. Despite the numerous public health campaigns and the efforts undertaken in the last decade regarding the establishment of a rapid diagnostic and an efficient treatment for these patients, the long-term prognosis has not been significantly improved. Thus, numerous studies were conducted in order to establish a more accurate prognosis, tumor infiltrating lymphocytes (TILs) being considered in many studies as independent prognostic factors of lymph node metastasis and overall survival in patients with melanoma...
May 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28728868/pdl1-expression-in-desmoplastic-melanoma-is-associated-with-tumor-aggressiveness-and-progression
#9
Stefan Kraft, Maria-Teresa Fernandez-Figueras, Nina A Richarz, Keith T Flaherty, Mai P Hoang
BACKGROUND: The prognostic role of programmed death ligand 1 (PDL1), CD8, and forkhead box p3 (FoxP3) expression in desmoplastic melanomas is unclear. METHODS: We correlated PDL1, p53, and Ki-67 expression with CD8(+) and FoxP3(+) immune infiltrates with clinicopathologic variables and patient outcomes in a series of 66 desmoplastic melanomas. RESULTS: Tumoral PDL1 expression (≥25%), which was seen in 21% of patients (14 of 66), significantly correlated with mixed histology, tumor thickness, mitoses, recurrence, and metastasis...
July 17, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28728856/achaete-scute-complex-homologue-2-accelerates-the-development-of-sj%C3%A3-gren-s-syndrome-like-disease-in-the-nod-shiltj-mouse
#10
Sung-Min Kim, Jeong-Eun Kwon, Jin-Sil Park, Hyeon-Beom Seo, Kyung-Ah Jung, Young-Mee Moon, Jennifer Lee, Seung-Ki Kwok, Mi-La Cho, Sung-Hwan Park
Achaete-scute complex homologue 2 (Ascl2) has been reported to induce the differentiation and activation of follicular helper T (TFH) cells, which are essential for development of Sjögren's syndrome (SS). This study examined whether Ascl2 plays a role in the development of SS. NOD/ShiLtJ mice were injected with an Ascl2-overexpression vector, and the infiltration of lymphocytes into salivary and lacrimal glands was assessed. The expression of inflammatory cytokines and chemoattractants for T or B cells was measured...
July 17, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28725958/immune-surveillance-plays-a-role-in-locally-aggressive-giant-cell-lesions-of-bone
#11
REVIEW
Ahmad Al-Sukaini, Francis J Hornicek, Zachary S Peacock, Leonard B Kaban, Soldano Ferrone, Joseph H Schwab
BACKGROUND: Giant cell lesions are locally aggressive intraosseous neoplasms with capacity to metastasize. The role of immune surveillance in the pathophysiology of giant cell lesions is poorly understood, and understanding what role the immune system plays in giant cell lesions may lead to the development of more effective treatment. The aim of this study was to explore the role of immune surveillance in giant cell lesions by examining the expression of the HLA class I and class II antigens and tumor infiltrating lymphocytes...
July 19, 2017: Clinical Orthopaedics and related Research
https://www.readbyqxmd.com/read/28724802/partially-exhausted-tumor-infiltrating-lymphocytes-predict-response-to-combination-immunotherapy
#12
Kimberly Loo, Katy K Tsai, Kelly Mahuron, Jacqueline Liu, Mariela L Pauli, Priscila M Sandoval, Adi Nosrati, James Lee, Lawrence Chen, Jimmy Hwang, Lauren S Levine, Matthew F Krummel, Alain P Algazi, Michael D Alvarado, Michael D Rosenblum, Adil I Daud
BACKGROUND: Programmed death 1 (PD-1) inhibition activates partially exhausted cytotoxic T lymphocytes (peCTLs) and induces tumor regression. We previously showed that the peCTL fraction predicts response to anti-PD-1 monotherapy. Here, we sought to correlate peCTL and regulatory T lymphocyte (Treg) levels with response to combination immunotherapy, and with demographic/disease characteristics, in metastatic melanoma patients. METHODS: Pretreatment melanoma samples underwent multiparameter flow cytometric analysis...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28723667/resistance-to-ctla-4-checkpoint-inhibition-reversed-through-selective-elimination-of-granulocytic-myeloid-cells
#13
Paul E Clavijo, Ellen C Moore, Jianhong Chen, Ruth J Davis, Jay Friedman, Young Kim, Carter Van Waes, Zhong Chen, Clint T Allen
PURPOSE: Local immunosuppression remains a critical problem that limits clinically meaningful response to checkpoint inhibition in patients with head and neck cancer. Here, we assessed the impact of MDSC elimination on responses to CTLA-4 checkpoint inhibition. EXPERIMENTAL DESIGN: Murine syngeneic carcinoma immune infiltrates were characterized by flow cytometry. Granulocytic MDSCs (gMDSCs) were depleted and T-lymphocyte antigen-specific responses were measured...
June 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723659/data-driven-analysis-of-immune-infiltrate-in-a-large-cohort-of-breast-cancer-and-its-association-with-disease-progression-er-activity-and-genomic-complexity
#14
Ruth Dannenfelser, Marianne Nome, Andliena Tahiri, Josie Ursini-Siegel, Hans Kristian Moen Vollan, Vilde D Haakensen, Åslaug Helland, Bjørn Naume, Carlos Caldas, Anne-Lise Børresen-Dale, Vessela N Kristensen, Olga G Troyanskaya
The tumor microenvironment is now widely recognized for its role in tumor progression, treatment response, and clinical outcome. The intratumoral immunological landscape, in particular, has been shown to exert both pro-tumorigenic and anti-tumorigenic effects. Identifying immunologically active or silent tumors may be an important indication for administration of therapy, and detecting early infiltration patterns may uncover factors that contribute to early risk. Thus far, direct detailed studies of the cell composition of tumor infiltration have been limited; with some studies giving approximate quantifications using immunohistochemistry and other small studies obtaining detailed measurements by isolating cells from excised tumors and sorting them using flow cytometry...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722673/expression-and-clinical-association-of-programmed-cell-death-1-programmed-death-ligand-1-and-cd8-lymphocytes-in-primary-sarcomas-is-subtype-dependent
#15
Anke E M van Erp, Yvonne M H Versleijen-Jonkers, Melissa H S Hillebrandt-Roeffen, Laurens van Houdt, Mark A J Gorris, Laura S van Dam, Thomas Mentzel, Marije E Weidema, C Dilara Savci-Heijink, Ingrid M E Desar, Hans H M Merks, Max M van Noesel, Janet Shipley, Winette T A van der Graaf, Uta E Flucke, Friederike A G Meyer-Wentrup
In order to explore the potential of immune checkpoint blockade in sarcoma, we investigated expression and clinical relevance of programmed cell death-1 (PD-1), programmed death ligand-1 (PD-L1) and CD8 in tumors of 208 sarcoma patients. Primary untreated osteosarcoma (n = 46), Ewing sarcoma (n = 32), alveolar rhabdomyosarcoma (n = 20), embryonal rhabdomyosarcoma (n = 77), synovial sarcoma (n = 22) and desmoplastic small round cell tumors (DSRCT) (n = 11) were examined immunohistochemically. PD-L1 expression was predominantly detected in alveolar and embryonal rhabdomyosarcomas (15% and 16%, respectively)...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722666/tumor-pd-l1-status-and-cd8-tumor-infiltrating-t-cells-markers-of-improved-prognosis-in-oropharyngeal-cancer
#16
Astrid De Meulenaere, Tijl Vermassen, Sandrine Aspeslagh, Philippe Deron, Fréderic Duprez, Debby Laukens, Jo Van Dorpe, Liesbeth Ferdinande, Sylvie Rottey
INTRODUCTION: The aim of this study was to evaluate the expression of PD-L1 in oropharyngeal squamous cell carcinoma. Its relation with clinicopathological variables such as amount and type of tumor infiltrating lymphocytes, HPV status and survival was also determined. RESULTS: Positive PD-L1 status for the SP142 clone related with improved overall survival in oropharyngeal squamous cell carcinoma. Tumors heavily infiltrated by tumor infiltrating lymphocytes were also linked with better outcome, and this as well for the total number of tumor infiltrating lymphocytes as for the CD3+ and CD8+ T cell count...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28718360/inflammatory-myopathy-in-horses-with-chronic-piroplasmosis
#17
Maria P Pasolini, Teresa B Pagano, Alessandro Costagliola, Davide De Biase, Barbara Lamagna, Luigi Auletta, Gerardo Fatone, Michele Greco, Pierpaolo Coluccia, Veneziano Veneziano, Claudio Pirozzi, Giuseppina Mattace Raso, Pasquale Santoro, Giuseppe Manna, Serenella Papparella, Orlando Paciello
Horses affected by chronic piroplasmosis may develop poor performance and muscle atrophy. Here we investigate the pathological and immunopathological aspects of myopathy occurring in chronic equine piroplasmosis. The study included 16 horses serologically positive for equine piroplasms presenting with clinical signs and supporting serum biochemical evidence of a myopathy. Skeletal muscle was evaluated by histopathology, immunohistochemistry, indirect immunofluorescence, and molecular detection of piroplasms and inflammatory cytokines in skeletal muscle...
January 1, 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/28716985/two-microrna-signatures-for-malignancy-and-immune-infiltration-predict-overall-survival-in-advanced-epithelial-ovarian-cancer
#18
Ilya Korsunsky, Janaki Parameswaran, Iuliana Shapira, John Lovecchio, Andrew Menzin, Jill Whyte, Lisa Dos Santos, Sharon Liang, Tawfiqul Bhuiya, Mary Keogh, Houman Khalili, Cassandra Pond, Anthony Liew, Andrew Shih, Peter K Gregersen, Annette T Lee
MicroRNAs have been established as key regulators of tumor gene expression and as prime biomarker candidates for clinical phenotypes in epithelial ovarian cancer (EOC). We analyzed the coexpression and regulatory structure of microRNAs and their co-localized gene targets in primary tumor tissue of 20 patients with advanced EOC in order to construct a regulatory signature for clinical prognosis. We performed an integrative analysis to identify two prognostic microRNA/mRNA coexpression modules, each enriched for consistent biological functions...
July 17, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28716484/the-anti-tumor-activity-of-the-stat3-inhibitor-stx-0119-occurs-via-promotion-of-tumor-infiltrating-lymphocyte-accumulation-in-temozolomide-resistant-glioblastoma-cell-line
#19
Yasuto Akiyama, Chizu Nonomura, Tadashi Ashizawa, Akira Iizuka, Ryota Kondou, Haruo Miyata, Takashi Sugino, Koichi Mitsuya, Nakamasa Hayashi, Yoko Nakasu, Akira Asai, Mamoru Ito, Yoshio Kiyohara, Ken Yamaguchi
STAT3 is considered to be a key molecule to mediating tumor-induced immunosuppression in various manners at tumor sites, by acting through immune-regulatory cytokines derived from the tumor cells. Specific anti-STAT3 inhibitors have been developed using nude mouse models transplanted with human tumor cells. However, mouse systems cannot accurately represent the human immune response induced by STAT3 inhibitors, and more humanized therapeutic model based on human immune cells and tumors are needed. In the present study, an immune-deficient NOG mouse with the deletion of both MHC-class I and class II genes, an MHC-double knockout mouse (dKO-NOG), was developed and used to establish humanized immunotherapeutic model...
July 15, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28710334/stem-cell-released-oncolytic-herpes-simplex-virus-has-therapeutic-efficacy-in-brain-metastatic-melanomas
#20
Wanlu Du, Ivan Seah, Oumaima Bougazzoul, GiHun Choi, Katrina Meeth, Marcus W Bosenberg, Hiroaki Wakimoto, David Fisher, Khalid Shah
The recent Food and Drug Administration approval of immunogenic oncolytic virus (OV) has opened a new era in the treatment of advanced melanoma; however, approximately 50% of patients with melanoma develop brain metastasis, and currently there are no beneficial treatment options for such patients. To model the progression of metastases seen in patients and to overcome the hurdles of systemic delivery of OV, we developed melanoma brain metastasis models in immunocompromised and immunocompetent mice, and tested the fate and efficacy of oncolytic herpes simplex virus (oHSV)-armed mesenchymal stem cells (MSCs)...
July 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
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