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TIL&isolation

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https://www.readbyqxmd.com/read/29769722/bystander-cd8-t-cells-are-abundant-and-phenotypically-distinct-in-human-tumour-infiltrates
#1
Yannick Simoni, Etienne Becht, Michael Fehlings, Chiew Yee Loh, Si-Lin Koo, Karen Wei Weng Teng, Joe Poh Sheng Yeong, Rahul Nahar, Tong Zhang, Hassen Kared, Kaibo Duan, Nicholas Ang, Michael Poidinger, Yin Yeng Lee, Anis Larbi, Alexis J Khng, Emile Tan, Cherylin Fu, Ronnie Mathew, Melissa Teo, Wan Teck Lim, Chee Keong Toh, Boon-Hean Ong, Tina Koh, Axel M Hillmer, Angela Takano, Tony Kiat Hon Lim, Eng Huat Tan, Weiwei Zhai, Daniel S W Tan, Iain Beehuat Tan, Evan W Newell
Various forms of immunotherapy, such as checkpoint blockade immunotherapy, are proving to be effective at restoring T cell-mediated immune responses that can lead to marked and sustained clinical responses, but only in some patients and cancer types1-4 . Patients and tumours may respond unpredictably to immunotherapy partly owing to heterogeneity of the immune composition and phenotypic profiles of tumour-infiltrating lymphocytes (TILs) within individual tumours and between patients5,6 . Although there is evidence that tumour-mutation-derived neoantigen-specific T cells play a role in tumour control2,4,7-10 , in most cases the antigen specificities of phenotypically diverse tumour-infiltrating T cells are largely unknown...
May 16, 2018: Nature
https://www.readbyqxmd.com/read/29743124/effects-of-habitat-fragmentation-on-the-genetic-diversity-and-differentiation-of-dendrolimus-punctatus-lepidoptera-lasiocampidae-in-thousand-island-lake-china-based-on-mitochondrial-coi-gene-sequences
#2
K Lv, J-R Wang, T-Q Li, J Zhou, J-Q Gu, G-X Zhou, Z-H Xu
Thousand Island Lake (TIL) is a typical fragmented landscape and an ideal model to study ecological effects of fragmentation. Partial fragments of the mitochondrial cytochrome oxidase subunit I gene of 23 island populations of Dendrolimus punctatus in TIL were sequenced, 141 haplotypes being identified. The number of haplotypes increased significantly with the increase in island area and shape index, whereas no significant correlation was detected between three island attributes (area, shape and isolation) and haplotype diversity...
May 10, 2018: Bulletin of Entomological Research
https://www.readbyqxmd.com/read/29712685/novel-effector-phenotype-of-tim-3-regulatory-t-cells-leads-to-enhanced-suppressive-function-in-head-and-neck-cancer-patients
#3
Zhuqing Liu, Elizabeth L McMichael, Gulidanna Shayan, Jing Li, Kevin Chen, Raghvendra M Srivastava, Lawrence P Kane, Binfeng Lu, Robert L Ferris
PURPOSE: Regulatory T (Treg) cells are important suppressive cells among tumor infiltrating lymphocytes (TIL). Treg express the well-known immune checkpoint receptor PD-1, which is reported to mark "exhausted" Treg with lower suppressive function. T cell immunoglobulin mucin (Tim)-3, a negative regulator of Th1 immunity, is expressed by a sizeable fraction of TIL Tregs, but the functional status of Tim-3+ Tregs remains unclear. EXPERIMENTAL DESIGN: CD4+CTLA-4+CD25high Treg were sorted from freshly excised head and neck squamous cell carcinoma (HNSCC) TIL based on Tim-3 expression...
April 30, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29710374/peri-tumoural-granulomatous-reaction-in-endometrial-carcinoma-association-with-dna-mismatch-repair-protein-deficiency-particularly-loss-of-pms2-expression
#4
Colin Jr Stewart, Amy Pearn, Nicholas Pachter, Adeline Tan
AIMS: The observation of peri-tumoural granulomatous reactions (PGRs) in two endometrial carcinomas (ECs) with a PMS2-deficient/ MLH1-intact expression pattern led us to investigate whether PGRs in EC were specifically associated with DNA mismatch repair (MMR) protein deficiency, particularly PMS2 loss. METHODS AND RESULTS: Hysterectomy specimens from 22 MMR protein-intact and 54 MMR protein-deficient ECs were reviewed with specific attention to the presence of a PGR and a tumour-associated lymphoid reaction (including tumour-infiltrating lymphocytes (TILs) and stromal lymphoid infiltrates)...
April 30, 2018: Histopathology
https://www.readbyqxmd.com/read/29688262/t-cells-isolated-from-patients-with-checkpoint-inhibitor-resistant-melanoma-are-functional-and-can-mediate-tumor-regression
#5
R Andersen, T H Borch, A Draghi, A Gokuldass, M A H Rana, M Pedersen, M Nielsen, P Kongsted, J W Kjeldsen, M C W Westergaard, H D Radic, C A Chamberlain, L R Hölmich, H W Hendel, M S Larsen, Ö Met, I M Svane, M Donia
Background: The majority of patients with metastatic melanoma obtain only short-term or no benefit at all from checkpoint inhibitor (CPI) immunotherapy. In this study, we investigated whether the immune system of patients progressing following CPI treatment was able to generate functional tumor-specific immune responses. Materials and methods: Tumor-infiltrating lymphocytes (TILs) were isolated and expanded from metastatic melanoma lesions which progressed during or after anti-PD-1 and anti-CTLA-4 treatment...
April 24, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29576222/blocking-tim-3-or-and-pd-1-reverses-dysfunction-of-tumor-infiltrating-lymphocytes-in-hbv-related-hepatocellular-carcinoma
#6
Furong Liu, Gucheng Zeng, Shaotang Zhou, Xiaoshun He, Nianfeng Sun, Xiaofeng Zhu, Anbin Hu
BACKGROUND: The immunosuppression of tumor-infiltrating lymphocytes (TILs) is associated with rapid progression of hepatitis B virus-related hepatocellular carcinoma (HBV-HCC). T cell Ig- and mucin-domain-containing molecule-3 (Tim-3) and programmed cell death 1 (PD-1) are important inhibitory molecules expressed on the surface of T cells, but their roles in the function of TILs in HBV-HCC are poorly understood. We aimed to study the roles of these two markers in HBV-HCC. METHODS: Ninety patients with pathologically confirmed HBV-associated HCC were enrolled in our study...
March 22, 2018: Bulletin du Cancer
https://www.readbyqxmd.com/read/29506120/granulosa-cells-from-human-primordial-and-primary-follicles-show-differential-global-gene-expression-profiles
#7
E H Ernst, S Franks, K Hardy, P Villesen, K Lykke-Hartmann
STUDY QUESTION: Can novel genetic candidates involved in follicle dormancy, activation and integrity be identified from transcriptomic profiles of isolated granulosa cells from human primordial and primary follicles? SUMMARY ANSWER: The granulosa cell compartment of the human primordial and primary follicle was extensively enriched in signal transducer and activator of transcription 3 (STAT3) and cAMP-response element binding protein (CREB) signalling, and several other putative signalling pathways that may also be mediators of follicle growth and development were identified...
April 1, 2018: Human Reproduction
https://www.readbyqxmd.com/read/29437767/t-cell-exhaustion-signatures-vary-with-tumor-type-and-are-severe-in-glioblastoma
#8
Karolina Woroniecka, Pakawat Chongsathidkiet, Kristen E Rhodin, Hanna R Kemeny, Cosette A Dechant, Samuel H Farber, Aladine A Elsamadicy, Xiuyu Cui, Shohei Koyama, Christina C Jackson, Landon J Hansen, Tanner M Johanns, Luis Sanchez-Perez, Vidyalakshmi Chandramohan, Yen-Rei A Yu, Darell D Bigner, Amber J Giles, Patrick Healy, Glenn Dranoff, Kent J Weinhold, Gavin P Dunn, Peter E Fecci
PURPOSE: T cell dysfunction is a hallmark of GBM. While anergy and tolerance have been well characterized, T cell exhaustion remains relatively unexplored. Exhaustion, characterized in part by the upregulation of multiple immune checkpoints, is a known contributor to failures amidst immune checkpoint blockade, a strategy that has lacked success thus far in GBM. This study is among the first to examine, and credential as bona fide, exhaustion among T cells infiltrating human and murine GBM...
February 7, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29399404/frequent-adaptive-immune-responses-against-arginase-1
#9
Evelina Martinenaite, Rasmus Erik Johansson Mortensen, Morten Hansen, Morten Orebo Holmström, Shamaila Munir Ahmad, Nicolai Grønne Dahlager Jørgensen, Özcan Met, Marco Donia, Inge Marie Svane, Mads Hald Andersen
The enzyme arginase-1 reduces the availability of arginine to tumor-infiltrating immune cells, thus reducing T-cell functionality in the tumor milieu. Arginase-1 is expressed by some cancer cells and by immune inhibitory cells, such as myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), and its expression is associated with poor prognosis. In the present study, we divided the arginase-1 protein sequence into overlapping 20-amino-acid-long peptides, generating a library of 31 peptides covering the whole arginase-1 sequence...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29392704/flow-cytometric-identification-of-tumor-infiltrating-lymphocytes-from-glioblastoma
#10
Karolina Woroniecka, Pakawat Chongsathidkiet, Aladine Elsamadicy, Harrison Farber, Xiuyu Cui, Peter E Fecci
We describe an isolation method of tumor-infiltrating lymphocytes (TILs) from glioblastoma tumors for the purpose of analysis by flow cytometry. This protocol is unique from many others in that the use of a selective lymphocyte isolation procedure, such as a Ficoll or Percoll gradient, is not used. We find that staining of TILs and analysis by flow cytometry is not affected by the presence of heterogeneous populations, while other selective isolation procedures can significantly decrease lymphocyte yield from already rare populations...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29301752/t-cell-responses-in-the-microenvironment-of-primary-renal-cell-carcinoma-implications-for-adoptive-cell-therapy
#11
Rikke Andersen, Marie Christine Wulff Westergaard, Julie Westerlin Kjeldsen, Anja Müller, Natasja Wulff Pedersen, Sine Reker Hadrup, Özcan Met, Barbara Seliger, Bjarne Kromann-Andersen, Thomas Hasselager, Marco Donia, Inge Marie Svane
In vitro expansion of large numbers of highly potent tumor-reactive T cells appears a prerequisite for effective adoptive cell therapy (ACT) with autologous tumor-infiltrating lymphocytes (TIL) as shown in metastatic melanoma (MM). We therefore sought to determine whether renal cell carcinomas (RCC) are infiltrated with tumor-reactive T cells that could be efficiently employed for adoptive transfer immunotherapy. TILs and autologous tumor cell lines (TCL) were successfully generated from 22 (92%) and 17 (77%) of 24 consecutive primary RCC specimens and compared with those generated from metastatic melanoma...
February 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29188500/metastasectomy-for-tumor-infiltrating-lymphocytes-an-emerging-operative-indication-in-surgical-oncology
#12
Joseph G Crompton, Nicholas Klemen, Udai S Kammula
Adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TILs) is an emerging immunotherapy for metastatic cancer. Surgeons play a central role in ACT treatments by performing resection of tumors from which TILs are isolated. It is important that surgeons have familiarity with this emerging treatment method because it is increasingly performed for an expanding variety of solid tumors at institutions around the world. This report offers a brief introduction to ACT for cancer, highlights historical milestones in its development, and provides patient selection and operative considerations for surgeons called upon to perform metastasectomy for the purpose of isolating TILs...
February 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29174843/an-efficient-single-cell-rna-seq-approach-to-identify-neoantigen-specific-t-cell-receptors
#13
Yong-Chen Lu, Zhili Zheng, Paul F Robbins, Eric Tran, Todd D Prickett, Jared J Gartner, Yong F Li, Satyajit Ray, Zulmarie Franco, Valery Bliskovsky, Peter C Fitzgerald, Steven A Rosenberg
The adoptive transfer of neoantigen-reactive tumor-infiltrating lymphocytes (TILs) can result in tumor regression in patients with metastatic cancer. To improve the efficacy of adoptive T cell therapy targeting these tumor-specific mutations, we have proposed a new therapeutic strategy, which involves the genetic modification of autologous T cells with neoantigen-specific T cell receptors (TCRs) and the transfer of these modified T cells back to cancer patients. However, the current techniques to isolate neoantigen-specific TCRs are labor intensive, time consuming, and technically challenging, not suitable for clinical applications...
February 7, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29147628/trial-watch-adoptively-transferred-cells-for-anticancer-immunotherapy
#14
REVIEW
Carole Fournier, François Martin, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi, Lionel Apetoh
Immunotherapies aimed at strengthening immune effector responses against malignant cells are growing at exponential rates. Alongside, the impressive benefits obtained by patients with advanced melanoma who received adoptively transferred tumor-infiltrating lymphocytes (TILs) have encouraged the scientific community to pursue adoptive cell transfer (ACT)-based immunotherapy. ACT involves autologous or allogenic effector lymphocytes that are generally obtained from the peripheral blood or resected tumors, expanded and activated ex vivo , and administered to lymphodepleted patients...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29113296/mesothelin-as-a-novel-biomarker-and-immunotherapeutic-target-in-human-glioblastoma
#15
Zhenjiang Liu, Martin Rao, Thomas Poiret, Silvia Nava, Qingda Meng, Anna von Landenberg, Jiri Bartek, Shanshan Xie, Georges Sinclair, Inti Peredo, Ernest Dodoo, Markus Maeurer
Glioblastoma multiforme (GBM) presents the most malignant form of glioma, with a 5-year survival rate below 3% despite standard therapy. Novel immune-based therapies in improving treatment outcomes in GBM are therefore warranted. Several molecularly defined targets have been identified mediating anti-GBM cellular immune responses. Mesothelin is a tumor-associated antigen (TAA) which is expressed in several solid tumors with different histology. Here, we report the immunological significance of mesothelin in human malignant glioma...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29067023/selection-of-shared-and-neoantigen-reactive-t-cells-for-adoptive-cell-therapy-based-on-cd137-separation
#16
Sivan Seliktar-Ofir, Efrat Merhavi-Shoham, Orit Itzhaki, Sharon Yunger, Gal Markel, Jacob Schachter, Michal J Besser
Adoptive cell therapy (ACT) of autologous tumor infiltrating lymphocytes (TIL) is an effective immunotherapy for patients with solid tumors, yielding objective response rates of around 40% in refractory patients with metastatic melanoma. Most clinical centers utilize bulk, randomly isolated TIL from the tumor tissue for ex vivo expansion and infusion. Only a minor fraction of the administered T cells recognizes tumor antigens, such as shared and mutation-derived neoantigens, and consequently eliminates the tumor...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29036438/a-selective-sphingosine-1-phosphate-receptor-1-agonist-sew-2871-aggravates-gastric-cancer-by-recruiting-myeloid-derived-suppressor-cells
#17
Yujing Zhou, Feng Guo
The immune status of tumor microenvironment in gastric cancer is poorly understood, which limits the development of novel strategies in this field. Sphingosine-1-phosphate (S1P) acts as an immune modulator, but the role of S1P in gastric cancer is elusive. Here, we aim to investigate S1P receptor 1 (S1P1)-mediated effect of S1P in gastric cancer. We generated a xenograft mouse model and used SEW-2871, a S1P1 specific agonist to activate S1P1 signalling. Tumor-infiltrating lymphocytes (TILs) were isolated and analysed using flow cytometry...
January 1, 2018: Journal of Biochemistry
https://www.readbyqxmd.com/read/29021139/paxillin-binding-to-the-cytoplasmic-domain-of-cd103-promotes-cell-adhesion-and-effector-functions-for-cd8-resident-memory-t-cells-in-tumors
#18
Ludiane Gauthier, Stéphanie Corgnac, Marie Boutet, Gwendoline Gros, Pierre Validire, Georges Bismuth, Fathia Mami-Chouaib
CD8+ /CD103+ tissue-resident memory T cells (TRM cells) accumulate in several human solid tumors, where they have been associated with a favorable prognosis. However, the role of CD103, the α subunit of the integrin αE β7 (also known as CD103), in the retention and functions of these TRM is undefined. In this report, we investigated the role of CD103 cytoplasmic domain and the focal adhesion-associated protein paxillin (Pxn) in downstream signaling and functional activities triggered through αE /CD103 chain...
December 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28854595/dormancy-and-activation-of-human-oocytes-from-primordial-and-primary-follicles-molecular-clues-to-oocyte-regulation
#19
E H Ernst, M L Grøndahl, S Grund, K Hardy, A Heuck, L Sunde, S Franks, C Y Andersen, P Villesen, K Lykke-Hartmann
STUDY QUESTION: Do specific transcriptome dynamics in human oocytes from primordial and primary follicles identify novel pathways in oocyte activation? SUMMARY ANSWER: The transcriptomic profiles in oocytes from primordial and primary follicles, respectively, revealed several new canonical pathways as putative mediators of oocyte dormancy and activation. WHAT IS KNOWN ALREADY: Cellular signaling pathways including PI3K/AKT and AKT/mTOR as well as TGF-β and IGF signaling are known to regulate the primordial-to-primary transition in mammalian follicle development...
August 1, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28825599/treg-depletion-potentiates-checkpoint-inhibition-in-claudin-low-breast-cancer
#20
Nicholas A Taylor, Sarah C Vick, Michael D Iglesia, W June Brickey, Bentley R Midkiff, Karen P McKinnon, Shannon Reisdorf, Carey K Anders, Lisa A Carey, Joel S Parker, Charles M Perou, Benjamin G Vincent, Jonathan S Serody
Claudin-low breast cancer is an aggressive subtype that confers poor prognosis and is found largely within the clinical triple-negative group of breast cancer patients. Here, we have shown that intrinsic and immune cell gene signatures distinguish the claudin-low subtype clinically as well as in mouse models of other breast cancer subtypes. Despite adaptive immune cell infiltration in claudin-low tumors, treatment with immune checkpoint inhibitory antibodies against cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed death receptor 1 (PD-1) were ineffective in controlling tumor growth...
September 1, 2017: Journal of Clinical Investigation
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