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Oncoimmunology

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https://www.readbyqxmd.com/read/28533942/hla-a24-ligandome-analysis-of-colon-and-lung-cancer-cells-identifies-a-novel-cancer-testis-antigen-and-a-neoantigen-that-elicits-specific-and-strong-ctl-responses
#1
Vitaly Kochin, Takayuki Kanaseki, Serina Tokita, Sho Miyamoto, Yosuke Shionoya, Yasuhiro Kikuchi, Daichi Morooka, Yoshihiko Hirohashi, Tomohide Tsukahara, Kazue Watanabe, Shingo Toji, Yasuo Kokai, Noriyuki Sato, Toshihiko Torigoe
This study focused on HLA-A24 and comprehensively analyzed the ligandome of colon and lung cancer cells without the use of MHC-binding in silico prediction algorithms. Affinity purification using the antibody specific to HLA-A24 followed by LC-MS/MS sequencing was used to detect peptides, which harbored the known characteristics of HLA-A24 peptides in terms of length and anchor motifs. Ligandome analysis demonstrated the natural presentation of two different types of novel tumor-associated antigens. The ligandome contained a peptide derived from SUV39H2, a gene found to be expressed in a variety of cancers but not in normal tissues (except for the testis)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507814/erratum
#2
(no author information available yet)
[This corrects the article DOI: 10.1080/2162402X.2016.1249558.].
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507813/deep-exploration-of-the-immune-infiltrate-and-outcome-prediction-in-testicular-cancer-by-quantitative-multiplexed-immunohistochemistry-and-gene-expression-profiling
#3
Peter J Siska, Romany A N Johnpulle, Alice Zhou, Jennifer Bordeaux, Ju Young Kim, Bashar Dabbas, Naveen Dakappagari, Jeffrey C Rathmell, W Kimryn Rathmell, Alicia K Morgans, Justin M Balko, Douglas B Johnson
Platinum-based chemotherapy is usually curative for patients with testicular germ cell tumors (TGCT), but a subset of patients experience disease progression and poor clinical outcomes. Here, we tested whether immune profiling of TGCT could identify novel prognostic markers and therapeutic targets for this patient cohort. We obtained primary and metastatic TGCT samples from one center. We performed immune profiling using multiplexed fluorescence immunohistochemistry (FIHC) for T-cell subsets and immune checkpoints, and targeted gene expression profiling (Nanostring nCounter Immune panel)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507812/a-barf1-specific-mab-as-a-new-immunotherapeutic-tool-for-the-management-of-ebv-related-tumors
#4
Riccardo Turrini, Anna Merlo, Debora Martorelli, Damiana Antonia Faè, Roberta Sommaggio, Isabella Monia Montagner, Vito Barbieri, Oriano Marin, Paola Zanovello, Riccardo Dolcetti, Antonio Rosato
The use of monoclonal antibodies (mAb) for the diagnosis and treatment of malignancies is acquiring an increasing clinical importance, thanks to their specificity, efficacy and relative easiness of use. However, in the context of Epstein-Barr virus (EBV)-related malignancies, only cancers of B-cell origin can benefit from therapeutic mAb targeting specific B-cell lineage antigens. To overcome this limitation, we generated a new mAb specific for BARF1, an EBV-encoded protein with transforming and immune-modulating properties...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507811/adoptive-natural-killer-cell-therapy-is-effective-in-reducing-pulmonary-metastasis-of-ewing-sarcoma
#5
Alexander A Tong, Hasan Hashem, Saada Eid, Frederick Allen, Daniel Kingsley, Alex Y Huang
The survival of patients with metastatic or relapsed Ewing sarcoma (ES) remains dismal despite intensification of combination chemotherapy and radiotherapy, precipitating the need for novel alternative therapies with minimal side effects. Natural killer (NK) cells are promising additions to the field of cellular immunotherapy. Adoptive NK cell therapy has shown encouraging results in hematological malignancies. Despite these initial promising successes, however, NK cell therapy for solid tumors remains to be investigated using in vivo tumor models...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507810/tie-2-expressing-monocytes-in-human-cancers
#6
Riccardo Turrini, Angélique Pabois, Ioannis Xenarios, George Coukos, Jean-François Delaloye, Marie-Agnès Doucey
Tumor-associated macrophages (TAM) are well known as a key player in the tumor microenvironment, which support cancer progression. More recently, a lineage of monocytes characterized by the expression of the TIE-2/Tek angiopoietin receptor identified a subset of circulating and tumor-associated monocytes endowed with proangiogenic activity. TIE-2 expressing monocytes (TEM) were found both in humans and mice. Here, we review the phenotypes and functions of TEM reported so far in human cancer and their potential use as markers of cancer progression and metastasis...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507809/t-cell-therapy-targeting-a-public-neoantigen-in-microsatellite-instable-colon-cancer-reduces-in-vivo-tumor-growth
#7
Else M Inderberg, Sébastien Wälchli, Marit R Myhre, Sissel Trachsel, Hilde Almåsbak, Gunnar Kvalheim, Gustav Gaudernack
T-cell receptor (TCR) transfer is an attractive strategy to increase the number of cancer-specific T cells in adoptive cell therapy. However, recent clinical and pre-clinical findings indicate that careful consideration of the target antigen is required to limit the risk of off-target toxicity. Directing T cells against mutated proteins such as frequently occurring frameshift mutations may thus be a safer alternative to tumor-associated self-antigens. Furthermore, such frameshift mutations result in novel polypeptides allowing selection of TCRs from the non-tolerant T-cell repertoire circumventing the problem of low affinity TCRs due to central tolerance...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507808/pro-necrotic-molecules-impact-local-immunosurveillance-in-human-breast-cancer
#8
Gautier Stoll, Yuting Ma, Heng Yang, Oliver Kepp, Laurence Zitvogel, Guido Kroemer
Necrosis culminates in spilling cellular content through the permeabilized plasma membrane, thereby releasing potentially immunostimulatory molecules in the pericellular space of dead cells. Accordingly, molecules involved in necroptotic signaling, such as receptor-interacting serine/threonine-protein kinase 3 (RIPK3) and mixed lineage kinase-like (MLKL) have been found to stimulate anticancer immune responses in mouse models of chemotherapy. mRNAs encoding prominent pro-necrotic gene products (RIPK1, RIPK3, MLKL, PGAM5 and DFNA5) were correlated with immune-related metagenes in several cancer types (breast, colorectal, lung, ovary, melanoma), revealing the strongest associations in breast cancer...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507807/host-antitumor-resistance-improved-by-the-macrophage-polarization-in-a-chimera-model-of-patients-with-hcc
#9
Akira Asai, Yusuke Tsuchimoto, Hideko Ohama, Shinya Fukunishi, Yasuhiro Tsuda, Makiko Kobayashi, Kazuhide Higuchi, Fujio Suzuki
Despite major advances in curative and palliative approaches, hepatocellular carcinoma (HCC) is still the third leading cause of cancer-related death worldwide. M1 macrophages (Mϕ) play a key role in host antitumor defenses in HCC. In our study, CD14(+) cells were isolated from the peripheral blood of four groups of HCC patients (group-1, patients with stage 0 HCC; group-2, patients with stage A HCC; group-3, patients with stage B HCC; and group-4, patients with stage C HCC) and characterized phenotypically...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507806/preclinical-efficacy-of-immune-checkpoint-monotherapy-does-not-recapitulate-corresponding-biomarkers-based-clinical-predictions-in-glioblastoma
#10
Abhishek D Garg, Lien Vandenberk, Matthias Van Woensel, Jochen Belmans, Marco Schaaf, Louis Boon, Steven De Vleeschouwer, Patrizia Agostinis
Glioblastoma (GBM) is resistant to most multimodal therapies. Clinical success of immune-checkpoint inhibitors (ICIs) has spurred interest in applying ICIs targeting CTLA4, PD1 or IDO1 against GBM. This amplifies the need to ascertain GBM's intrinsic susceptibility (or resistance) toward these ICIs, through clinical biomarkers that may also "guide and prioritize" preclinical testing. Here, we interrogated the TCGA and/or REMBRANDT human patient-cohorts to predict GBM's predisposition toward ICIs. We exploited various broad clinical biomarkers, including mutational or predicted-neoantigen burden, pre-existing or basal levels of tumor-infiltrating T lymphocytes (TILs), differential expression of immune-checkpoints within the tumor and their correlation with particular TILs/Treg-associated functional signature and prognostic impact of differential immune-checkpoint expression...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507805/generation-and-functional-characterization-of-mdsc-like-cells
#11
Annkristin Heine, Stefanie Andrea Erika Held, Jonas Schulte-Schrepping, Julia Friederike Andrea Wolff, Kathrin Klee, Thomas Ulas, Niklas Arndt Schmacke, Solveig Nora Daecke, Kati Riethausen, Joachim L Schultze, Peter Brossart
Myeloid-derived suppressor cells (MDSC) are critical in regulating immune responses by suppressing antigen presenting cells (APC) and T cells. We previously observed that incubation of peripheral blood monocytes with interleukin (IL)-10 during their differentiation to monocyte-derived dendritic cells (moDCs) results in the generation of an APC population with a CD14(+)HLA-DR(low)phenotype (IL-10-APC) with reduced stimulatory capacity similar to human MDSC. Co-incubation experiments now revealed that the addition of IL-10-APC to moDC caused a reduction of DC-induced T-cell proliferation, of the expression of maturation markers, and of secreted cytokines and chemokines such as TNF-α, IL-6, MIP-1α and Rantes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507804/hla-dependent-immune-escape-mechanisms-in-b-cell-lymphomas-implications-for-immune-checkpoint-inhibitor-therapy
#12
Marcel Nijland, Rianne N Veenstra, Lydia Visser, Chuanhui Xu, Kushi Kushekhar, Gustaaf W van Imhoff, Philip M Kluin, Anke van den Berg, Arjan Diepstra
Antigen presentation by tumor cells in the context of Human Leukocyte Antigen (HLA) is generally considered to be a prerequisite for effective immune checkpoint inhibitor therapy. We evaluated cell surface HLA class I, HLA class II and cytoplasmic HLA-DM staining by immunohistochemistry (IHC) in 389 classical Hodgkin lymphomas (cHL), 22 nodular lymphocyte predominant Hodgkin lymphomas (NLPHL), 137 diffuse large B-cell lymphomas (DLBCL), 39 primary central nervous system lymphomas (PCNSL) and 19 testicular lymphomas...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507803/pd-l1-expression-on-malignant-cells-is-no-prerequisite-for-checkpoint-therapy
#13
Jan Willem Kleinovink, Koen A Marijt, Mark J A Schoonderwoerd, Thorbald van Hall, Ferry Ossendorp, Marieke F Fransen
Immunotherapy with PD-1/PD-L1-blocking antibodies is clinically effective for several tumor types, but the mechanism is not fully understood. PD-L1 expression on tumor biopsies is generally regarded as an inclusion criterion for this cancer therapy. Here, we describe the PD-L1-blocking therapeutic responses of preclinical tumors in which PD-L1 expression was removed from cancer cells, but not from immune infiltrate. Lack of PD-L1 expression on malignant cells delayed tumor outgrowth in a CD8(+) T cell-mediated fashion, showing the importance of this molecule in immune suppression...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507802/b-cells-and-the-humoral-response-in-melanoma-the-overlooked-players-of-the-tumor-microenvironment
#14
REVIEW
Giulia Chiaruttini, Silvia Mele, James Opzoomer, Silvia Crescioli, Kristina M Ilieva, Katie E Lacy, Sophia N Karagiannis
Evidence of tumor-resident mature B cell and antibody compartments and reports of associations with favorable prognosis in malignant melanoma suggest that humoral immunity could participate in antitumor defense. Likely striving to confer immunological protection while being subjected to tumor-promoting immune tolerance, B cells may engender multiple functions, including antigen processing and presentation, cytokine-mediated signaling, antibody class switching, expression and secretion. We review key evidence in support of multifaceted immunological mechanisms by which B cells may counter or contribute to malignant melanoma, and we discuss their potential translational implications...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507801/the-novel-negative-checkpoint-regulator-vista-is-expressed-in-gastric-carcinoma-and-associated-with-pd-l1-pd-1-a-future-perspective-for-a-combined-gastric-cancer-therapy
#15
Christine Böger, Hans-Michael Behrens, Sandra Krüger, Christoph Röcken
A combined blockade of V-domain Ig suppressor of T-cell activation (VISTA) and PD-1 is a promising new cancer treatment option, which was efficient in murine tumor models and is currently tested in first phase I studies. Here, we analyzed the VISTA expression in a large and well-characterized gastric cancer (GC) cohort on 464 therapy-naive GC samples and 14 corresponding liver metastases using immunohistochemistry. Staining results were correlated with clinico-pathological characteristics, genetic alterations and survival...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507800/formyl-peptide-receptor-1-suppresses-gastric-cancer-angiogenesis-and-growth-by-exploiting-inflammation-resolution-pathways
#16
Nella Prevete, Federica Liotti, Anna Illiano, Angela Amoresano, Piero Pucci, Amato de Paulis, Rosa Marina Melillo
Chronic inflammation can result from inadequate engagement of resolution mechanisms, mainly accomplished by specialized pro-resolving mediators (SPMs) arising from the metabolic activity of lipoxygenases (ALOX5/15) on ω-6 or ω-3 essential polyunsaturated fatty acids (PUFA). We previously demonstrated that formyl peptide receptor 1 (FPR1) suppresses gastric cancer (GC) by inhibiting its inflammatory/angiogenic potential. In this study, we asked whether FPR1 exploits inflammation resolution pathways to suppress GC angiogenesis and growth...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507799/characterization-of-a-human-anti-tumoral-nk-cell-population-expanded-after-bcg-treatment-of-leukocytes
#17
Eva M García-Cuesta, Gloria Esteso, Omodele Ashiru, Sheila López-Cobo, Mario Álvarez-Maestro, Ana Linares, Mei M Ho, Luis Martínez-Piñeiro, Hugh T Reyburn, Mar Valés-Gómez
Immunotherapy, via intra-vesical instillations of BCG, is the therapy of choice for patients with high-risk non-muscle invasive bladder cancer. The subsequent recruitment of lymphocytes and myeloid cells, as well as the release of cytokines and chemokines, is believed to induce a local immune response that eliminates these tumors, but the detailed mechanisms of action of this therapy are not well understood. Here, we have studied the phenotype and function of the responding lymphocyte populations as well as the spectrum of cytokines and chemokines produced in an in vitro model of human peripheral blood mononuclear cells (PBMCs) co-cultured with BCG...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507798/tumor-infiltrating-neutrophils-predict-benefit-from-adjuvant-chemotherapy-in-patients-with-muscle-invasive-bladder-cancer
#18
Lin Zhou, Le Xu, Lingli Chen, Qiang Fu, Zheng Liu, Yuan Chang, Zongming Lin, Jiejie Xu
Growing evidence shows tumor-infiltrating neutrophils (TINs) involvement in tumorigenesis. The objective of this study is to assess the prognostic effect of TINs and its impact on adjuvant chemotherapy benefits in muscle invasive bladder cancer (MIBC). A total of 142 MIBC patients from Zhongshan Hospital, 119 MIBC patients from FUSCC, and 405 MIBC patients from TCGA cohort were enrolled in the study. TINs were evaluated by immunohistochemical staining of CD66b or the CIBERSORT method. Patients with high TINs had a significantly poorer overall survival (p = 0...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507797/il15-induces-a-potent-antitumor-activity-in-nk-cells-isolated-from-malignant-pleural-effusions-and-overcomes-the-inhibitory-effect-of-pleural-fluid
#19
D Croxatto, S Martini, L Chiossone, F Scordamaglia, C F Simonassi, L Moretta, M C Mingari, P Vacca
Natural Killer (NK) cells are capable of recognizing and killing cancer cells and play an important role in tumor immunosurveillance. However, tumor-infiltrating NK cells are frequently impaired in their functional capability. A remarkable exception is represented by NK cells isolated from malignant pleural effusions (PE) that are not anergic and, upon IL2-induced activation, efficiently kill tumor cells. Although IL2 is used in various clinical trials, severe side effects may occur in treated patients. In this study, we investigated whether also other clinical-grade cytokines could induce strong cytotoxicity in NK cells isolated from pleural fluid of patients with primary or metastatic tumors of different origins...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507796/lyg1-exerts-antitumor-function-through-promoting-the-activation-proliferation-and-function-of-cd4-t-cells
#20
Huihui Liu, Yanfei Zhang, Zhengyang Liu, Pingzhang Wang, Xiaoning Mo, Weiwei Fu, Wanchang Liu, Yingying Cheng, Wenling Han
Identification of novel stimulatory cytokines with antitumor function would have great value in tumor immunotherapy investigations. Here, we report LYG1 (Lysozyme G-like 1) identified through the strategy of Immunogenomics as a novel classical secretory protein with tumor-inhibiting function. LYG1 recombinant protein (rhLYG1) could significantly suppress the growth of B16 tumors in WT B6 mice, but not in SCID-beige mice, Rag1(-/-) mice, CD4(+)- or CD8(+) T cell-deleted mice. It could increase the number of CD4(+) and CD8(+) T cells in tumor-infiltrating lymphocytes, tumor-draining lymph nodes, and spleens, and promote IFNγ production by T cells in tumor-bearing mice...
2017: Oncoimmunology
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