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Cancer Immunology, Immunotherapy: CII

Joseph M Obeid, Nolan A Wages, Yinin Hu, Donna H Deacon, Craig L Slingluff
INTRODUCTION: Infiltration of non-small-cell lung cancer (NSCLC) by CD8(+) T lymphocytes predicts improved patient survival; however, heterogeneity of intratumoral localization complicates this assessment. Strategies for tumor sampling may not accurately represent the whole tumor. We hypothesized that sampling strategies may alter the identification of tumors with high CD8 density and affect the prognostic significance. PATIENTS AND METHODS: Twenty-three primary NSCLC tumors were immunohistochemically stained for CD8 and were assessed using automated software with eight different sampling strategies or the whole tumor...
October 21, 2016: Cancer Immunology, Immunotherapy: CII
Young Kwang Chae, Lauren Chiec, Nisha Mohindra, Ryan Gentzler, Jyoti Patel, Francis Giles
Immune checkpoint inhibitors such as pembrolizumab, ipilimumab, and nivolumab, now FDA-approved for use in treating several types of cancer, have been associated with immune-related adverse effects. Specifically, the antibodies targeting the programmed-cell death-1 immune checkpoint, pembrolizumab and nivolumab, have been rarely reported to induce the development of type 1 diabetes mellitus. Here we describe a case of a patient who developed antibody-positive type 1 diabetes mellitus following treatment with pembrolizumab in combination with systemic chemotherapy for metastatic adenocarcinoma of the lung...
October 19, 2016: Cancer Immunology, Immunotherapy: CII
Wataru Obara, Takashi Karashima, Kazuyoshi Takeda, Renpei Kato, Yoichiro Kato, Mitsugu Kanehira, Ryo Takata, Keiji Inoue, Toyomasa Katagiri, Taro Shuin, Yusuke Nakamura, Tomoaki Fujioka
PURPOSE: Through genome-wide expression profile analysis, hypoxia-inducible protein 2 (HIG2) has previously been identified as an oncoprotein involved in development/progression of renal cell carcinoma (RCC). We subsequently identified a highly immunogenic HLA-A*0201/0206-restricted epitope peptide (HIG2-9-4) corresponding to a part of HIG2 and applied it as a therapeutic vaccine. We conducted a phase I clinical trial using the HIG2-9-4 peptide for patients with advanced RCC. MATERIALS AND METHODS: Nine patients having HLA-A*0201 or HLA-A*0206 with metastatic or unresectable RCC after failure of the cytokine and/or tyrosine kinase inhibitor therapies were enrolled in this study...
October 18, 2016: Cancer Immunology, Immunotherapy: CII
Andrew Zloza, Neal D Dharmadhikari, Erica J Huelsmann, Joseph R Broucek, Tasha Hughes, Frederick J Kohlhapp, Howard L Kaufman
Recombinant interleukin-2 (rIL-2) is associated with objective responses in 15-20 % of patients with metastatic melanoma and renal cell carcinoma. More recently, rIL-2 has also demonstrated improved clinical activity in patients with melanoma. Given the toxicity of high-dose rIL-2 and the availability of many new immunotherapy agents, it has been suggested that lower doses of rIL-2 may be preferred for combination clinical studies. In order to determine the impact of low doses of rIL-2 on anti-tumor immunity and therapeutic effectiveness, we challenged C57BL/6 mice with poorly immunogenic B16-F10 melanoma and treated them with varying doses of rIL-2 (range 10(3)-10(5) IU)...
October 18, 2016: Cancer Immunology, Immunotherapy: CII
Peter L Stern, Richard Harrop
The natural history of a patient's cancer is often characterised by genetic diversity and sequential sweeps of clonal dominance. It is therefore not surprising that identifying the most appropriate tumour-associated antigen for targeted intervention is challenging. The 5T4 oncofoetal antigen was identified by searching for surface molecules shared between human trophoblast and cancer cells with the rationale that they may function to allow survival of the foetus as a semi-allograft in the mother or a tumour in its host...
October 18, 2016: Cancer Immunology, Immunotherapy: CII
Dan Ishihara, Laurentiu Pop, Tsuguhide Takeshima, Puneeth Iyengar, Raquibul Hannan
Cancer immunotherapy exploits the immune system's ability to differentiate between tumor target cells and host cells. Except for limited success against a few tumor types, most immunotherapies have not achieved the desired clinical efficacy until recently. The field of cancer immunotherapy has flourished with a variety of new agents for clinical use, and remarkable progress has been made in the design of effective immunotherapeutic regimens. Furthermore, the therapeutic outcome of these novel agents is enhanced when combined with conventional cancer treatment modalities including radiotherapy (RT)...
October 14, 2016: Cancer Immunology, Immunotherapy: CII
Jason Miska, Aida Rashidi, Alan L Chang, Megan E Muroski, Yu Han, Lingjiao Zhang, Maciej S Lesniak
Regulatory T cells (Tregs) are potently immunosuppressive cells that accumulate within the glioma microenvironment. The reduction in their function and/or trafficking has been previously shown to enhance survival in preclinical models of glioma. Glucocorticoid-induced TNFR-related protein (GITR) is a tumor necrosis factor superfamily receptor enriched on Tregs that has shown promise as a target for immunotherapy. An agonistic antibody against GITR has been demonstrated to inhibit Tregs in a number of models and has only been recently addressed in glioma...
October 12, 2016: Cancer Immunology, Immunotherapy: CII
Anning Li, Yue Wu, Jenny Linnoila, Benjamin Pulli, Cuihua Wang, Matthias Zeller, Muhammad Ali, Grant K Lewandrowski, Jinghui Li, Benoit Tricot, Edmund Keliher, Gregory R Wojtkiewicz, Giulia Fulci, Xiaoyuan Feng, Bakhos A Tannous, Zhenwei Yao, John W Chen
Currently, there is no stable and flexible method to label and track cytotoxic T lymphocytes (CTLs) in vivo in CTL immunotherapy. We aimed to evaluate whether the sulfo-hydroxysuccinimide (NHS)-biotin-streptavidin (SA) platform could chemically modify the cell surface of CTLs for in vivo tracking. CD8+ T lymphocytes were labeled with sulfo-NHS-biotin under different conditions and then incubated with SA-Alexa647. Labeling efficiency was proportional to sulfo-NHS-biotin concentration. CD8+ T lymphocytes could be labeled with higher efficiency with sulfo-NHS-biotin in DPBS than in RPMI (P < 0...
October 8, 2016: Cancer Immunology, Immunotherapy: CII
Ajjai Alva, Gregory A Daniels, Michael K K Wong, Howard L Kaufman, Michael A Morse, David F McDermott, Joseph I Clark, Sanjiv S Agarwala, Gerald Miletello, Theodore F Logan, Ralph J Hauke, Brendan Curti, John M Kirkwood, Rene Gonzalez, Asim Amin, Mayer Fishman, Neeraj Agarwal, James N Lowder, Hong Hua, Sandra Aung, Janice P Dutcher
High-dose interleukin-2 (HD IL-2) was approved for treatment of metastatic renal cell carcinoma (mRCC) in 1992 and for metastatic melanoma (mM) in 1998, in an era predating targeted therapies and immune checkpoint inhibitors. The PROCLAIM(SM) registry was established to collect and analyze data for patients treated with HD IL-2 in the current era. This analysis includes 170 patients with mM and 192 patients with mRCC treated between 2005 and 2012 with survival data current as of July 27, 2015. For patients with mM, complete response (CR) was observed in 5 %, partial response (PR) in 10 %, stable disease (SD) in 22 %, and 63 % had progressive disease (PD)...
October 6, 2016: Cancer Immunology, Immunotherapy: CII
Peter Ellmark, Sara M Mangsbo, Christina Furebring, Per Norlén, Thomas H Tötterman
The most important goals for the field of immuno-oncology are to improve the response rate and increase the number of tumor indications that respond to immunotherapy, without increasing adverse side effects. One approach to achieve these goals is to use tumor-directed immunotherapy, i.e., to focus the immune activation to the most relevant part of the immune system. This may improve anti-tumor efficacy as well as reduce immune-related adverse events. Tumor-directed immune activation can be achieved by local injections of immune modulators in the tumor area or by directing the immune modulator to the tumor using bispecific antibodies...
October 6, 2016: Cancer Immunology, Immunotherapy: CII
John O Richards, Alex J Albers, Thomas S Smith, Judy A Tjoe
No abstract text is available yet for this article.
October 1, 2016: Cancer Immunology, Immunotherapy: CII
Wei Wang, Amy K Erbe, Mikayla Gallenberger, KyungMann Kim, Lakeesha Carmichael, Dustin Hess, Eneida A Mendonca, Yiqiang Song, Jacquelyn A Hank, Su-Chun Cheng, Sabina Signoretti, Michael Atkins, Alexander Carlson, Jonathan M Weiss, James Mier, David Panka, David F McDermott, Paul M Sondel
NK cells play a role in many cancer immunotherapies. NK cell activity is tightly regulated by killer immunoglobulin-like receptor (KIR) and KIR-ligand interactions. Inhibitory KIR-ligands have been identified as HLA molecules, while activating KIR-ligands are largely unknown. Individuals that have not inherited the corresponding KIR-ligand for at least one inhibitory KIR gene are termed the "KIR-ligand missing" genotype, and they are thought to have a subset of NK cells that express inhibitory KIRs for which the corresponding KIR-ligand is missing on autologous tissue, and thus will not be inhibited through KIR-ligand recognition...
September 30, 2016: Cancer Immunology, Immunotherapy: CII
Emily A Lanzel, M Paula Gomez Hernandez, Amber M Bates, Christopher N Treinen, Emily E Starman, Carol L Fischer, Deepak Parashar, Janet M Guthmiller, Georgia K Johnson, Taher Abbasi, Shireen Vali, Kim A Brogden
PURPOSE: Interaction of the programmed death-1 (PD-1) co-receptor on T cells with the programmed death-ligand 1 (PD-L1) on tumor cells can lead to immunosuppression, a key event in the pathogenesis of many tumors. Thus, determining the amount of PD-L1 in tumors by immunohistochemistry (IHC) is important as both a diagnostic aid and a clinical predictor of immunotherapy treatment success. Because IHC reactivity can vary, we developed computational simulation models to accurately predict PD-L1 expression as a complementary assay to affirm IHC reactivity...
September 29, 2016: Cancer Immunology, Immunotherapy: CII
Yasuharu Akasaki, Tetsuro Kikuchi, Sadamu Homma, Shigeo Koido, Toshifumi Ohkusa, Tetsunori Tasaki, Kazumi Hayashi, Hideo Komita, Nobuyuki Watanabe, Yuta Suzuki, Yohei Yamamoto, Ryosuke Mori, Takao Arai, Toshihide Tanaka, Tatsuhiro Joki, Takaaki Yanagisawa, Yuichi Murayama
BACKGROUND: This trial was designed to evaluate the safety and clinical responses to a combination of temozolomide (TMZ) chemotherapy and immunotherapy with fusions of DCs and glioma cells in patients with glioblastoma (GBM). METHOD: GBM patients were assigned to two groups: a group of recurrent GBMs after failing TMZ-chemotherapy against the initially diagnosed glioma (Group-R) or a group of newly diagnosed GBMs (Group-N). Autologous cultured glioma cells obtained from surgical specimens were fused with autologous DCs using polyethylene glycol...
September 29, 2016: Cancer Immunology, Immunotherapy: CII
Lydia Dyck, Mieszko M Wilk, Mathilde Raverdeau, Alicja Misiak, Louis Boon, Kingston H G Mills
The co-inhibitory molecule PD-1 suppresses T cell responses and has been targeted in the treatment of cancer. Here, we examined the role of PD-1 in regulating the balance between regulatory and effector T cells and whether blocking PD-1 could enhance tumour vaccine-induced protective immunity. A significantly higher proportion of tumour-resident T cells expressed PD-1 and Foxp3 compared with T cells in the tumour circulation or draining lymph nodes, and this correlated with a lower frequency of IFN-γ- and TNF-secreting CD8 T cells...
September 28, 2016: Cancer Immunology, Immunotherapy: CII
Toshiko Kamata, Akane Suzuki, Naoko Mise, Fumie Ihara, Mariko Takami, Yuji Makita, Atsushi Horinaka, Kazuaki Harada, Naoki Kunii, Shigetoshi Yoshida, Ichiro Yoshino, Toshinori Nakayama, Shinichiro Motohashi
The role of invariant natural killer T (iNKT) cells in antitumor immunity has been studied extensively, and clinical trials in patients with advanced cancer have revealed a prolonged survival in some cases. In recent years, humanized blocking antibodies against co-stimulatory molecules such as PD-1 have been developed. The enhancement of T cell function is reported to improve antitumor immunity, leading to positive clinical effects. However, there are limited data on the role of PD-1/programmed death ligand (PDL) molecules in human iNKT cells...
September 15, 2016: Cancer Immunology, Immunotherapy: CII
Sarah Maria Johler, Jörg Fuchs, Guido Seitz, Sorin Armeanu-Ebinger
Macrophage migration inhibitory factor (MIF) is known to be involved in oncogenic transformation, tumour progression, and immunosuppression and is overexpressed in many solid tumours, including paediatric rhabdomyosarcoma (RMS). We investigated the function of MIF in RMS during treatment with cytotoxic drugs. RMS cell lines were analysed by flow cytometry, immunofluorescence staining, and ELISA. We demonstrated the overexpression of MIF in RMS cells and the enhanced expression and secretion after treatment with cytotoxic agents...
September 15, 2016: Cancer Immunology, Immunotherapy: CII
Mariëtte I E van Poelgeest, Valeria V Visconti, Zohara Aghai, Vanessa J van Ham, Moniek Heusinkveld, Maarten L Zandvliet, A Rob P M Valentijn, Renske Goedemans, Caroline E van der Minne, Els M E Verdegaal, J Baptist M Z Trimbos, Sjoerd H van der Burg, Marij J P Welters
Adoptive transfer of tumor-specific T cells, expanded from tumor-infiltrating lymphocytes or from peripheral blood, is a promising immunotherapeutic approach for the treatment of cancer. Here, we studied whether the tumor-draining lymph nodes (TDLN) of patients with human papillomavirus (HPV)-induced cervical cancer can be used as a source for ACT. The objectives were to isolate lymph node mononuclear cells (LNMC) from TDLN and optimally expand HPV-specific CD4+ and CD8+ T cells under clinical grade conditions...
September 12, 2016: Cancer Immunology, Immunotherapy: CII
Michele Maio, Erica Bertocci, Carolina Fazio, Carla Chiarucci, Ornella Cutaia, Elisa Scala, Gianluca Giacobini, Maria Fortunata Lofiego, Ester Fonsatti, Cristina Maccalli, Hugues J M G Nicolay, Giorgio Parmiani
No abstract text is available yet for this article.
September 12, 2016: Cancer Immunology, Immunotherapy: CII
Irina V Tiper, Tonya J Webb
Histone deacetylases (HDACs) are a family of enzymes that influence expression of genes implicated in tumor initiation, progression, and anti-tumor responses. In addition to their canonical role in deacetylation of histones, HDACs regulate many non-canonical targets, such as Signal Transducer and Activator of Transcription 3 (STAT3). We hypothesize that tumors use epigenetic mechanisms to dysregulate CD1d-mediated antigen presentation, thereby impairing the ability of natural killer T (NKT) cells to recognize and destroy malignant cells...
September 10, 2016: Cancer Immunology, Immunotherapy: CII
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