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tumor infiltrating t lymphocyte

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https://www.readbyqxmd.com/read/28641100/bruton-s-tyrosine-kinase-btk-as-a-promising-target-in-solid-tumors
#1
REVIEW
J Molina-Cerrillo, T Alonso-Gordoa, P Gajate, E Grande
Bruton's tyrosine kinase (BTK) is a non-receptor intracellular kinase that belongs to the TEC-family tyrosine kinases together with bone marrow-expressed kinase (BMX), redundant-resting lymphocyte kinase (RLK), and IL-2 inducible T-Cell kinase (ITK). All these proteins play a key role in the intracellular signaling of both B and T lymphocytes. Recently, some preclinical data have demonstrated that BTK is present in certain tumor subtypes and in other relevant cells that are contributing to the tumor microenvironment such as dendritic cells, macrophages, myeloid derived suppressor cells and endothelial cells...
June 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28634284/co-administration-of-rankl-and-ctla4-antibodies-enhances-lymphocyte-mediated-anti-tumor-immunity-in-mice
#2
Elizabeth Ahern, Heidi Harjunpaa, Deborah Barkauskas, Stacey Allen, Kazuyoshi Takeda, Hideo Yagita, David Wyld, William C Dougall, Michele W L Teng, Mark J Smyth
Purpose: Novel partners for established immune checkpoint inhibitors in the treatment of cancer are needed to address the problems of primary and acquired resistance. The efficacy of combination RANKL and CTLA4 blockade in anti-tumor immunity has been suggested by recent case reports in melanoma. Here we provide a rationale for this combination in mouse models of cancer. <br />Experimental Design: The efficacy and mechanism of a combination of RANKL and CTLA4 blockade was examined by tumor infiltrating lymphocyte analysis, tumor growth and metastasis using a variety of neutralizing antibodies and gene-targeted mice...
June 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28632936/peritumoral-cuffing-by-t-cell-tumor-infiltrating-lymphocytes-distinguishes-hpv-related-oropharyngeal-squamous-cell-carcinoma-from-oral-cavity-squamous-cell-carcinoma
#3
Kate Poropatich, David Hernandez, Joel Fontanarosa, Koshonna Brown, Gayle Woloschak, Ajit Paintal, Kirtee Raparia, Sandeep Samant
BACKGROUND: It is unclear why human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) has improved clinical behavior compared to HPV-negative HNSCC. We sought to better characterize the immune microenvironment of tongue cancers by examining the CD3 and CD8 TIL pattern in HPV-positive and -negative tumors. METHODS: Histologic sections from 40 oral tongue and oropharyngeal cases were analyzed (n= 21 HPV DNA-positive, n= 19 HPV DNA-negative)...
June 20, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/28629762/targeting-the-tumor-and-its-associated-stroma-one-and-one-can-make-three-in-adoptive-t-cell-therapy-of-solid-tumors
#4
Anna Mondino, Gerlanda Vella, Laura Icardi
Adoptive T cell therapy (ACT) has become a promising immunotherapeutic option for cancer patients. The proof for ACT therapeutic efficacy was first obtained with allogenic T cells and then reproduced with T cells isolated from patients' tumor samples (i.e. tumor-infiltrating lymphocytes). It is now clear that specificity of ACT products can be educated by genetically engineering T cells with classical T Cell Receptors (TCR) or chimeric antigen receptors (CAR). To date a poor accessibility of the tumor mass and a hostile microenvironment, influenced by genetic and epigenetic instability, mainly limit ACT therapeutic efficacy in the case of solid tumors...
June 15, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28628234/tumor-targeting-salmonella-typhimurium-a1-r-promotes-tumoricidal-cd8-t-cell-tumor-infiltration-and-arrests-growth-in-a-syngeneic-pancreatic-cancer-orthotopic-mouse-model
#5
Takashi Murakami, Yukihiko Hiroshima, Yong Zhang, Ming Zhao, Tasuku Kiyuna, Ho Kyoung Hwang, Kentaro Miyake, Yuki Homma, Ryutaro Mori, Ryusei Matsuyama, Takashi Chishima, Yasushi Ichikawa, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M Hoffman
The present study determined the effect of tumor-targeting Salmonella typhimurium (S. typhimurium) A1-R on CD8(+) tumor-infiltrating lymphocytes (TILs) in a syngeneic pancreatic cancer orthotopic mouse model. The effect of tumor-targeting Salmonella typhimurium A1-R on CD8(+) TILs was determined on Pan02 murine pancreatic adenocarcinoma cells implanted orthotopically on the pancreatic tail of C57BL/6 mice. Three weeks after orthotopic implantation, mice were randomized into G1: untreated control group (n = 8); and G2: Salmonella typhimurium A1-R treatment group (n = 8, 1 × 10(7) CFU/body, iv, weekly, 3 weeks)...
June 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28628092/tissue-resident-memory-features-are-linked-to-the-magnitude-of-cytotoxic-t-cell-responses-in-human-lung-cancer
#6
Anusha-Preethi Ganesan, James Clarke, Oliver Wood, Eva M Garrido-Martin, Serena J Chee, Toby Mellows, Daniela Samaniego-Castruita, Divya Singh, Grégory Seumois, Aiman Alzetani, Edwin Woo, Peter S Friedmann, Emma V King, Gareth J Thomas, Tilman Sanchez-Elsner, Pandurangan Vijayanand, Christian H Ottensmeier
Therapies that boost the anti-tumor responses of cytotoxic T lymphocytes (CTLs) have shown promise; however, clinical responses to the immunotherapeutic agents currently available vary considerably, and the molecular basis of this is unclear. We performed transcriptomic profiling of tumor-infiltrating CTLs from treatment-naive patients with lung cancer to define the molecular features associated with the robustness of anti-tumor immune responses. We observed considerable heterogeneity in the expression of molecules associated with activation of the T cell antigen receptor (TCR) and of immunological-checkpoint molecules such as 4-1BB, PD-1 and TIM-3...
June 19, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28626618/cytoplasmic-expression-of-c-myc-protein-is-associated-with-risk-stratification-of-mantle-cell-lymphoma
#7
Yi Gong, Xi Zhang, Rui Chen, Yan Wei, Zhongmin Zou, Xinghua Chen
AIM: To investigate the association of C-MYC protein expression and risk stratification in mantle cell lymphoma (MCL), and to evaluate the utility of C-MYC protein as a prognostic biomarker in clinical practice. METHODS: We conducted immunohistochemical staining of C-MYC, Programmed cell death ligand 1 (PD-L1), CD8, Ki-67, p53 and SRY (sex determining region Y) -11 (SOX11) to investigate their expression in 64 patients with MCL. The staining results and other clinical data were evaluated for their roles in risk stratification of MCL cases using ANOVA, Chi-square, and Spearman's Rank correlation coefficient analysis...
2017: PeerJ
https://www.readbyqxmd.com/read/28622514/landscape-of-infiltrating-t-cells-in-liver-cancer-revealed-by-single-cell-sequencing
#8
Chunhong Zheng, Liangtao Zheng, Jae-Kwang Yoo, Huahu Guo, Yuanyuan Zhang, Xinyi Guo, Boxi Kang, Ruozhen Hu, Julie Y Huang, Qiming Zhang, Zhouzerui Liu, Minghui Dong, Xueda Hu, Wenjun Ouyang, Jirun Peng, Zemin Zhang
Systematic interrogation of tumor-infiltrating lymphocytes is key to the development of immunotherapies and the prediction of their clinical responses in cancers. Here, we perform deep single-cell RNA sequencing on 5,063 single T cells isolated from peripheral blood, tumor, and adjacent normal tissues from six hepatocellular carcinoma patients. The transcriptional profiles of these individual cells, coupled with assembled T cell receptor (TCR) sequences, enable us to identify 11 T cell subsets based on their molecular and functional properties and delineate their developmental trajectory...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28614908/adenoviral-production-of-interleukin-2-at-the-tumor-site-removes-the-need-for-systemic-postconditioning-in-adoptive-cell-therapy
#9
Joao Manuel Santos, Riikka Havunen, Mikko Siurala, Víctor Cervera-Carrascon, Siri Tähtinen, Suvi Sorsa, Marjukka Anttila, Pauliina Karell, Anna Kanerva, Akseli Hemminki
Systemic high-dose interleukin-2 (IL-2) postconditioning has long been utilized in boosting the efficacy of T cells in adoptive cell therapy (ACT) of solid tumors. The resulting severe off-target toxicity of these regimens renders local production at the tumor an attractive concept with possible safety gains. We evaluated the efficacy and safety of intratumorally administered IL-2-coding adenoviruses in combination with tumor-infiltrating lymphocyte therapy in syngeneic Syrian hamsters bearing HapT1 pancreatic tumors and with T cell receptor transgenic ACT in B16...
June 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28614802/mitochondrial-dysregulation-and-glycolytic-insufficiency-functionally-impair-cd8-t-cells-infiltrating-human-renal-cell-carcinoma
#10
Peter J Siska, Kathryn E Beckermann, Frank M Mason, Gabriela Andrejeva, Allison R Greenplate, Adam B Sendor, Yun-Chen J Chiang, Armando L Corona, Lelisa F Gemta, Benjamin G Vincent, Richard C Wang, Bumki Kim, Jiyong Hong, Chiu-Lan Chen, Timothy N Bullock, Jonathan M Irish, W Kimryn Rathmell, Jeffrey C Rathmell
Cancer cells can inhibit effector T cells (Teff) through both immunomodulatory receptors and the impact of cancer metabolism on the tumor microenvironment. Indeed, Teff require high rates of glucose metabolism, and consumption of essential nutrients or generation of waste products by tumor cells may impede essential T cell metabolic pathways. Clear cell renal cell carcinoma (ccRCC) is characterized by loss of the tumor suppressor von Hippel-Lindau (VHL) and altered cancer cell metabolism. Here, we assessed how ccRCC influences the metabolism and activation of primary patient ccRCC tumor infiltrating lymphocytes (TIL)...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28613923/the-era-of-checkpoint-blockade-in-lung-cancer-taking-the-brakes-off-the-immune-system
#11
Edmund K Moon, Corey J Langer, Steven M Albelda
Despite recent advances with targeted kinase inhibitors and better tolerated chemotherapy, the treatment of metastatic non-small cell lung cancer (NSCLC) remains suboptimal. One recent advance that holds great promise is immunotherapy - an approach that enhances a patient's immune system to better recognize and react to abnormal cells. The most successful immunotherapeutic strategy to date uses antibodies to block inhibitory receptors (also called "checkpoints") that are upregulated on the T cells that infiltrate the tumor...
June 14, 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28611304/immune-profiling-of-nf1-associated-tumors-reveals-histologic-subtype-distinctions-and-heterogeneity-implications-for-immunotherapy
#12
Kellie B Haworth, Michael A Arnold, Christopher R Pierson, Kwangmin Choi, Nicholas D Yeager, Nancy Ratner, Ryan D Roberts, Jonathan L Finlay, Timothy P Cripe
Successful treatment of neurofibromatosis type 1 (NF1)-associated tumors poses a significant clinical challenge. While the primary underlying genetic defect driving RAS signaling is well described, recent evidence suggests immune dysfunction contributes to tumor pathogenesis and malignant transformation. As immunologic characterizations, prognostic and predictive of immunotherapeutic clinical response in other cancers, are not fully described for benign and malignant NF1-related tumors, we sought to define their immunologic profiles...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28611085/ccr6-cc-chemokine-receptor-6-is-essential-for-the-migration-of-detrimental-natural-interleukin-17-producing-%C3%AE-%C3%AE-t-cells-in-stroke
#13
Priyadharshini Arunachalam, Peter Ludewig, Patrick Melich, Thiruma Valavan Arumugam, Christian Gerloff, Immo Prinz, Tim Magnus, Mathias Gelderblom
BACKGROUND AND PURPOSE: Immune-mediated tissue damage after stroke evolves within the first days, and lymphocytes contribute to the secondary injury. Our goal was to identify T-cell subpopulations, which trigger the immune response. METHODS: In a model of experimental stroke, we analyzed the immune phenotype of interleukin-17 (IL-17)-producing γδ T cells and explored the therapeutic potential of neutralizing anti-IL-17 antibodies in combination with mild therapeutic hypothermia...
June 13, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28611044/characterization-of-mk-4166-a-clinical-agonistic-antibody-that-targets-human-gitr-and-inhibits-the-generation-and-suppressive-effects-of-t-regulatory-cells
#14
Selvakumar Sukumar, Douglas C Wilson, Ying Yu, Jerelyn Wong, Saraswathi Naravula, Grigori Ermakov, Romina Riener, Bhagyashree Bhagwat, Antoaneta S Necheva, Jeff Grein, Tatyana Churakova, Ruban Mangadu, Peter Georgiev, Denise Manfra, Elaine M Pinheiro, Venkataraman Sriram, Wendy J Bailey, Danuta Herzyk, Terrill K McClanahan, Aarron Willingham, Amy M Beebe, Svetlana Sadekova
GITR is a T cell co-stimulatory receptor that enhances cellular and humoral immunity. The agonist anti-mouse GITR antibody DTA-1 has demonstrated efficacy in murine models of cancer primarily by attenuation of Treg-mediated immune suppression, but the translatability to human GITR biology has not been fully explored. Here we report the potential utility of MK-4166, a humanized GITR monoclonal antibody selected to bind to an epitope analogous to the DTA-1 epitope, which enhances the proliferation of both naïve and tumor-infiltrating T lymphocytes (TILs)...
June 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28608409/neoadjuvant-chemoradiotherapy-of-pancreatic-cancer-induces-a-favorable-immunogenic-tumor-microenvironment-associated-with-increased-major-histocompatibility-complex-class-i-related-chain-a-b-expression
#15
Takashi Murakami, Yuki Homma, Ryusei Matsuyama, Ryutaro Mori, Kentaro Miyake, Yusaku Tanaka, Kanechika Den, Yoji Nagashima, Masatoshi Nakazawa, Yukihiko Hiroshima, Michio Ueda, Kuniya Tanaka, Robert M Hoffman, Michael Bouvet, Itaru Endo
BACKGROUND: Damage-associated molecular patterns (DAMPs) are related to immune responses in malignant tumors including tumor-infiltrating lymphocytes (TILs). The aim of the present study was to determine the relationship between expression of components of DAMPs and TILs in pancreatic cancer patients who underwent neoadjuvant chemoradiotherapy (NACRT) versus those who did not. METHODS: NACRT was administered to 51 patients with borderline-resectable pancreatic cancer and not to 33 patients with resectable pancreatic cancer...
June 12, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28607807/immunohistochemical-evaluation-of-vitamin-d-receptor-vdr-expression-in-cutaneous-melanoma-tissues-and-four-vdr-gene-polymorphisms
#16
Francesco La Marra, Giuseppe Stinco, Cinzia Buligan, Giovanni Chiriacò, Diego Serraino, Carla Di Loreto, Sabina Cauci
OBJECTIVE: : Vitamin D receptor (VDR) mediates vitamin D activity. We examined whether VDR expression in excised melanoma tissues is associated with VDR gene (VDR) polymorphisms. METHODS: : We evaluated VDR protein expression (by monoclonal antibody immunostaining), melanoma characteristics, and carriage of VDR-FokI-rs2228570 (C>T),VDR-BsmI-rs1544410 (G>A),VDR-ApaI-rs7975232 (T>G), andVDR-TaqI-rs731236 (T>C) polymorphisms (by restriction fragment length polymorphism)...
May 2017: Cancer Biology & Medicine
https://www.readbyqxmd.com/read/28603527/intratumoral-foxp3-helios-regulatory-t-cells-upregulating-immunosuppressive-molecules-are-expanded-in-human-colorectal-cancer
#17
Azharuddin Sajid Syed Khaja, Salman M Toor, Haytham El Salhat, Bassam R Ali, Eyad Elkord
Regulatory T cells (Tregs) can be antitumorigenic or pro-tumorigenic in colorectal cancer (CRC) depending on the presence of different Treg subsets with various immunosuppressive molecules. Some studies reported the phenotypic characteristics of tumor-infiltrating immune cells in CRC, but limited studies have focused on the co-expression of suppressive molecules on immune cells. The aim of this study was to characterize immune cells in the tumor microenvironment (TME), compared to paired adjacent non-tumor colon tissue of CRC patients...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28601728/do-tumor-infiltrating-lymphocytes-really-indicate-favorable-prognosis-in-epithelial-ovarian-cancer
#18
Nuri Yildirim, Levent Akman, Kamuran Acar, Sibel Demir, Sultan Ozkan, Nuran Alan, Osman Zekioglu, M Cosan Terek, Necmettin Ozdemir, Aydin Ozsaran
OBJECTIVE: The aim of this study is to evaluate the impact of lymphocyte infiltration on prognostic parameters, recurrence and survival in ovarian cancer. STUDY DESIGN: Sixty-two patients who were primarily operated for epithelial ovarian carcinoma between 1997 and 2008 were included. CD3, CD4, CD8, CD20 and FoxP3 expressions were evaluated immunohistochemically on sections obtained from paraffin-embedded tissues. RESULTS: Median follow up was 87 months...
June 4, 2017: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/28601064/types-of-immune-inflammatory-responses-as-a-reflection-of-cell-cell-interactions-under-conditions-of-tissue-regeneration-and-tumor-growth
#19
REVIEW
L A Tashireva, V M Perelmuter, V N Manskikh, E V Denisov, O E Savelieva, E V Kaygorodova, M V Zavyalova
Inflammatory infiltration of tumor stroma is an integral reflection of reactions that develop in response to any damage to tumor cells including immune responses to antigens or necrosis caused by vascular disorders. In this review, we use the term "immune-inflammatory response" (IIR) that allows us to give an integral assessment of the cellular composition of the tumor microenvironment. Two main types of IIRs are discussed: type 1 and 2 T-helper reactions (Th1 and Th2), as well as their inducers: immunosuppressive responses and reactions mediated by Th22 and Th17 lymphocytes and capable of modifying the main types of IIRs...
May 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28600479/trabectedin-overrides-osteosarcoma-differentiative-block-and-reprograms-the-tumor-immune-environment-enabling-effective-combination-with-immune-checkpoint-inhibitors
#20
Chiara Ratti, Laura Botti, Valeria Cancila, Silvia Galvan, Ilaria Torselli, Cecilia Garofalo, Maria Cristina Manara, Lucia Bongiovanni, Cesare F Valenti, Alessia Burocchi, Mariella Parenza, Barbara Cappetti, Sabina Sangaletti, Claudio Tripodo, Katia Scotlandi, Mario P Colombo, Claudia Chiodoni
Purpose: Osteosarcoma (OS), the most common primary bone tumor, is characterized by an aggressive behavior with high tendency to develop lung metastases as well as by multiple genetic aberrations that have hindered the development of targeted therapies. New therapeutic approaches are urgently needed; however, novel combinations with immunotherapies and checkpoint inhibitors require suitable preclinical models with intact immune systems to be properly tested. <p>Experimental Design: We have developed immuno-competent OS models that grow orthotopically in the bone and spontaneously metastasize to the lungs, mimicking human OS...
June 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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