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https://www.readbyqxmd.com/read/29301752/t-cell-responses-in-the-microenvironment-of-primary-renal-cell-carcinoma-implications-for-adoptive-cell-therapy
#1
Rikke Andersen, Marie Christine Wulff Westergaard, Julie Westerlin Kjeldsen, Anja Mueller, Natasja Wulff Pedersen, Sine Reker Hadrup, Ozcan 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 (TCLs) were successfully generated from 22 (92%) and 17 (77%) of 24 consecutive primary RCC specimens and compared to those generated from MM...
January 4, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29188500/metastasectomy-for-tumor-infiltrating-lymphocytes-an-emerging-operative-indication-in-surgical-oncology
#2
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...
November 29, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29174843/an-efficient-single-cell-rna-seq-approach-to-identify-neoantigen-specific-t-cell-receptors
#3
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...
October 28, 2017: 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
#4
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
#5
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
#6
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
#7
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 signaling. Tumor-infiltrating lymphocytes (TILs) were isolated and analyzed using flow cytometry...
October 3, 2017: 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
#8
Ludiane Gauthier, Stephanie 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 αEβ7 (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...
October 11, 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
#9
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
#10
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
https://www.readbyqxmd.com/read/28648905/antibodies-against-immune-checkpoint-molecules-restore%C3%A2-functions-of-tumor-infiltrating-t-cells-in-hepatocellular%C3%A2-carcinomas
#11
Guoying Zhou, Dave Sprengers, Patrick P C Boor, Michail Doukas, Hannah Schutz, Shanta Mancham, Alexander Pedroza-Gonzalez, Wojciech G Polak, Jeroen de Jonge, Marcia Gaspersz, Haidong Dong, Kris Thielemans, Qiuwei Pan, Jan N M IJzermans, Marco J Bruno, Jaap Kwekkeboom
BACKGROUND & AIMS: Ligand binding to inhibitory receptors on immune cells, such as programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA4), down-regulates the T-cell-mediated immune response (called immune checkpoints). Antibodies that block these receptors increase antitumor immunity in patients with melanoma, non-small-cell lung cancer, and renal cell cancer. Tumor-infiltrating CD4+ and CD8+ T cells in patients with hepatocellular carcinoma (HCC) have been found to be functionally compromised...
October 2017: Gastroenterology
https://www.readbyqxmd.com/read/28522749/expansion-of-tumor-infiltrating-cd8-t-cells-expressing-pd-1-improves-the-efficacy-of-adoptive-t-cell-therapy
#12
Sarita M Fernandez-Poma, Diego Salas-Benito, Teresa Lozano, Noelia Casares, Jose-Ignacio Riezu-Boj, Uxua Mancheño, Edurne Elizalde, Diego Alignani, Natalia Zubeldia, Itziar Otano, Enrique Conde, Pablo Sarobe, Juan Jose Lasarte, Sandra Hervas-Stubbs
Recent studies have found that tumor-infiltrating lymphocytes (TIL) expressing PD-1 can recognize autologous tumor cells, suggesting that cells derived from PD-1(+) TILs can be used in adoptive T-cell therapy (ACT). However, no study thus far has evaluated the antitumor activity of PD-1-selected TILs in vivo In two mouse models of solid tumors, we show that PD-1 allows identification and isolation of tumor-specific TILs without previous knowledge of their antigen specificities. Importantly, despite the high proportion of tumor-reactive T cells present in bulk CD8 TILs before expansion, only T-cell products derived from sorted PD-1(+), but not from PD-1(-) or bulk CD8 TILs, specifically recognized tumor cells...
July 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28443127/transcriptome-analysis-of-a-female-sterile-mutant-fsm-in-chinese-cabbage-brassica-campestris-ssp-pekinensis
#13
Shengnan Huang, Zhiyong Liu, Chengyu Li, Runpeng Yao, Danyang Li, Li Hou, Xiang Li, Wenjie Liu, Hui Feng
Female-sterile mutants are ideal materials for studying pistil development in plants. Here, we identified a female-sterile mutant fsm in Chinese cabbage. This mutant, which exhibited stable inheritance, was derived from Chinese cabbage DH line 'FT' using a combination of isolated microspore culture and ethyl methanesulfonate mutagenesis. Compared with the wild-type line 'FT,' the fsm plants exhibited pistil abortion, and floral organs were also relatively smaller. Genetic analysis indicated that the phenotype of fsm is controlled by a single recessive nuclear gene...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28377481/characterization-of-an-immunogenic-mutation-in-a-patient-with-metastatic-triple-negative-breast-cancer
#14
Yasmine Assadipour, Nikolaos Zacharakis, Jessica S Crystal, Todd D Prickett, Jared J Gartner, Robert P T Somerville, Hui Xu, Mary A Black, Li Jia, Harshini Chinnasamy, Isaac Kriley, Lily Lu, John R Wunderlich, Zhili Zheng, Yong-Chen Lu, Paul F Robbins, Steven A Rosenberg, Stephanie L Goff, Steven A Feldman
Purpose: The administration of autologous tumor-infiltrating lymphocytes (TILs) can mediate durable tumor regressions in patients with melanoma likely based on the recognition of immunogenic somatic mutations expressed by the cancer. There are limited data regarding the immunogenicity of mutations in breast cancer. We sought to identify immunogenic nonsynonymous mutations in a patient with triple-negative breast cancer (TNBC) to identify and isolate mutation-reactive TILs for possible use in adoptive cell transfer...
August 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28278692/habitat-fragmentation-influences-gene-structure-and-gene-differentiation-among-the-loxoblemmus-aomoriensis-populations-in-the-thousand-island-lake
#15
Kun Lv, Jing Zhou, Jian-Qiang Gu, Guo-Xing Zhou, Wei Wang, Zhi-Hong Xu
Thousand Island Lake (TIL) is a fragmented landscape consisting of more than 1000 land-bridge islands isolated during reservoir formation. To evaluate the effects of fragmentation and island attributes on insect populations, we examined the genetic structure of Loxoblemmus aomoriensis, a species of cricket widely distributed in TIL, and compared genetic diversity between islands samples. Population genetic analyses was conducted based on mitochondrial DNA haplotype frequencies of 10 sample islands. By comparing three island attributes with population genetic diversity reveals that island area influenced population genetic diversity (r(2 )=( )0...
February 16, 2017: Mitochondrial DNA. Part A. DNA Mapping, Sequencing, and Analysis
https://www.readbyqxmd.com/read/28226203/characteristic-changes-in-decidual-gene-expression-signature-in-spontaneous-term-parturition
#16
Haidy El-Azzamy, Andrea Balogh, Roberto Romero, Yi Xu, Christopher LaJeunesse, Olesya Plazyo, Zhonghui Xu, Theodore G Price, Zhong Dong, Adi L Tarca, Zoltan Papp, Sonia S Hassan, Tinnakorn Chaiworapongsa, Chong Jai Kim, Nardhy Gomez-Lopez, Nandor Gabor Than
BACKGROUND: The decidua has been implicated in the "terminal pathway" of human term parturition, which is characterized by the activation of pro-inflammatory pathways in gestational tissues. However, the transcriptomic changes in the decidua leading to terminal pathway activation have not been systematically explored. This study aimed to compare the decidual expression of developmental signaling and inflammation-related genes before and after spontaneous term labor in order to reveal their involvement in this process...
May 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28213366/tumor-infiltrating-and-peripheral-blood-t-cell-immunophenotypes-predict-early-relapse-in-localized-clear-cell-renal-cell-carcinoma
#17
Nicolas A Giraldo, Etienne Becht, Yann Vano, Florent Petitprez, Laetitia Lacroix, Pierre Validire, Rafael Sanchez-Salas, Alexandre Ingels, Stephane Oudard, Audrey Moatti, Benedicte Buttard, Sarah Bourass, Claire Germain, Xavier Cathelineau, Wolf H Fridman, Catherine Sautès-Fridman
Purpose: The efficacy of PD-1 checkpoint blockade as adjuvant therapy in localized clear cell renal cell carcinoma (ccRCC) is currently unknown. The identification of tumor microenvironment (TME) prognostic biomarkers in this setting may help define which patients could benefit from checkpoint blockade and uncover new therapeutic targets.Experimental Design: We performed multiparametric flow cytometric immunophenotypic analysis of T cells isolated from tumor tissue [tumor-infiltrating lymphocytes (TIL)], adjacent non-malignant renal tissue [renal-infiltrating lymphocytes (RIL)], and peripheral blood lymphocytes (PBL), in a cohort of patients (n = 40) with localized ccRCC...
August 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28197366/compensatory-upregulation-of-pd-1-lag-3-and-ctla-4-limits-the-efficacy-of-single-agent-checkpoint-blockade-in-metastatic-ovarian-cancer
#18
Ruea-Yea Huang, Ariel Francois, Aj Robert McGray, Anthony Miliotto, Kunle Odunsi
Tumor-associated or -infiltrating lymphocytes (TALs or TILs) co-express multiple immune inhibitory receptors that contribute to immune suppression in the ovarian tumor microenvironment (TME). Dual blockade of PD-1 along with LAG-3 or CTLA-4 has been shown to synergistically enhance T-cell effector function, resulting in a delay in murine ovarian tumor growth. However, the mechanisms underlying this synergy and the relative contribution of other inhibitory receptors to immune suppression in the ovarian TME are unknown...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28114254/adoptive-cell-therapy-for-metastatic-melanoma
#19
REVIEW
Efrat Merhavi-Shoham, Orit Itzhaki, Gal Markel, Jacob Schachter, Michal J Besser
Adoptive cell therapy (ACT) of tumor-infiltrating lymphocytes (TILs) is a powerful form of immunotherapy by inducing durable complete responses that significantly extend the survival of melanoma patients. Mutation-derived neoantigens were recently identified as key factors for tumor recognition and rejection by TILs. The isolation of T-cell receptor (TCR) genes directed against neoantigens and their retransduction into peripheral T cells may provide a new form of ACT.Genetic modifications of T cells with chimeric antigen receptors (CARs) have demonstrated remarkable clinical results in hematologic malignancies, but are so far less effective in solid tumors...
January 2017: Cancer Journal
https://www.readbyqxmd.com/read/28093446/tumor-infiltrating-merkel-cell-polyomavirus-specific-t-cells-are-diverse-and-associated-with-improved-patient-survival
#20
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...
February 2017: Cancer Immunology Research
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