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Cancer Immunology, Immunotherapy: CII

Ying Xiong, Li Liu, Yu Xia, Yangyang Qi, Yifan Chen, Lingli Chen, Peipei Zhang, Yunyi Kong, Yang Qu, Zewei Wang, Zhiyuan Lin, Xiang Chen, Zhuoyi Xiang, Jiajun Wang, Qi Bai, Weijuan Zhang, Yuanfeng Yang, Jianming Guo, Jiejie Xu
PURPOSE: Hypoxia-inducible factor 2α (HIF-2α) overexpression leads to activation of angiogenic pathways. However, little is known about the association between HIF-2α expression and anti-tumor immunity in clear cell renal cell carcinoma (ccRCC). We aimed to explore how HIF-2α influenced the microenvironment and the underlying mechanisms. EXPERIMENTAL DESIGN: We immunohistochemically evaluated immune cells infiltrations and prognostic value of HIF-2α expression in a retrospective Zhongshan Hospital cohort of 280 ccRCC patients...
February 13, 2019: Cancer Immunology, Immunotherapy: CII
Inge M Werter, Charlotte M Huijts, Sinéad M Lougheed, Paul Hamberg, Marco B Polee, Metin Tascilar, Maartje Los, John B A G Haanen, Helgi H Helgason, Henk M Verheul, Tanja D de Gruijl, Hans J van der Vliet
INTRODUCTION: Metastatic renal cell cancer (mRCC) patients have a median overall survival (mOS) of approximately 28 months. Until recently, mammalian target of rapamycin (mTOR) inhibition with everolimus was the standard second-line treatment regimen for mRCC patients, improving median progression-free survival (mPFS). Treatment with everolimus supports the expansion of immunosuppressive regulatory T cells (Tregs), which exert a negative effect on antitumor immune responses. In a phase 1 dose-escalation study, we have recently demonstrated that a low dose of 50 mg oral cyclophosphamide once daily can be safely combined with everolimus in mRCC patients and prevents the everolimus-induced increase in Tregs...
February 11, 2019: Cancer Immunology, Immunotherapy: CII
Linh T Nguyen, Samuel D Saibil, Valentin Sotov, Michael X Le, Leila Khoja, Danny Ghazarian, Luisa Bonilla, Habeeb Majeed, David Hogg, Anthony M Joshua, Michael Crump, Norman Franke, Anna Spreafico, Aaron Hansen, Ayman Al-Habeeb, Wey Leong, Alexandra Easson, Michael Reedijk, David P Goldstein, David McCready, Kazuhiro Yasufuku, Thomas Waddell, Marcelo Cypel, Andrew Pierre, Bianzheng Zhang, Sarah Boross-Harmer, Jane Cipollone, Megan Nelles, Elizabeth Scheid, Michael Fyrsta, Charlotte S Lo, Jessica Nie, Jennifer Y Yam, Pei Hua Yen, Diana Gray, Vinicius Motta, Alisha R Elford, Stephanie DeLuca, Lisa Wang, Stephanie Effendi, Ragitha Ellenchery, Naoto Hirano, Pamela S Ohashi, Marcus O Butler
Adoptive cell therapy using autologous tumor-infiltrating lymphocytes (TIL) has shown significant clinical benefit, but is limited by toxicities due to a requirement for post-infusion interleukin-2 (IL-2), for which high dose is standard. To assess a modified TIL protocol using lower dose IL-2, we performed a single institution phase II protocol in unresectable, metastatic melanoma. The primary endpoint was response rate. Secondary endpoints were safety and assessment of immune correlates following TIL infusion...
February 11, 2019: Cancer Immunology, Immunotherapy: CII
Dmitry A Aronov, Viacheslav V Zhukov, Svetlana G Semushina, Ekaterina V Moiseeva
The development of new approaches to breast cancer (BC) early diagnosis is an important objective of modern oncology. Although the role of the immune system in cancer initiation process was experimentally well established, the prognostic value of cellular blood immunological parameters (CBIPs) for BC onset prediction was not demonstrated either in clinics or in mouse models. In this study, we focused on revealing informative CBIPs for mammary cancer (MC) onset prediction in the BLRB/BYRB mouse model with a high incidence of natural MC development...
February 11, 2019: Cancer Immunology, Immunotherapy: CII
Ernest Nadal, Bartomeu Massuti, Manuel Dómine, Rosario García-Campelo, Manuel Cobo, Enriqueta Felip
Immune checkpoint inhibitors (ICIs) targeting the programmed cell death-1 (PD-1)-programmed cell death ligand-1 (PD-L1) axis have shown promising results in non-small cell lung cancer (NSCLC) patients, some of them with persistent responses to these agents that form a population of long-term survivors. Despite the variable definition of PD-L1 positivity in tumors, an association between expression and response has been reasonably consistent in advanced NSCLC. In addition, the clinical efficacy of ICIs seems to be related to the genomic landscape of the tumor in terms of mutational burden and clonal neoantigens...
February 6, 2019: Cancer Immunology, Immunotherapy: CII
Lorena P Suarez-Kelly, Kala M Levine, Thomas E Olencki, Sara E Martin Del Campo, Elizabeth A Streacker, Taylor R Brooks, Volodymyr I Karpa, Joseph Markowitz, Anissa K Bingman, Susan M Geyer, Kari L Kendra, William E Carson
No abstract text is available yet for this article.
February 6, 2019: Cancer Immunology, Immunotherapy: CII
Anna Felberg, Aleksandra Urban, Anna Borowska, Grzegorz Stasiłojć, Michał Taszner, Andrzej Hellmann, Anna Maria Blom, Marcin Okrój
Anti-CD20 monoclonal antibodies (mAbs) rituximab and ofatumumab are potent activators of the classical complement pathway, and have been approved for the treatment of B-cell malignancies. However, complement exhaustion and overexpression of complement inhibitors by cancer cells diminish their therapeutic potential. The strategies of targeting membrane complement inhibitors by function-blocking antibodies and the supplementation with fresh frozen plasma have been proposed to overcome tumour cell resistance. We present a novel approach, which utilizes gain-of-function variants of complement factor B (FB), a component of alternative C3/C5 convertases, which augment mAb-activated reactions through a positive feedback mechanism called an amplification loop...
February 6, 2019: Cancer Immunology, Immunotherapy: CII
Sandra P D'Angelo, Matthias Hunger, Andrew S Brohl, Paul Nghiem, Shailender Bhatia, Omid Hamid, Janice M Mehnert, Patrick Terheyden, Kent C Shih, Isaac Brownell, Céleste Lebbé, Karl D Lewis, Gerald P Linette, Michele Milella, Michael Schlichting, Meliessa H Hennessy, Murtuza Bharmal
BACKGROUND: Response rates are primary endpoints in many oncology trials; however, correlation with overall survival (OS) is not uniform across cancer types, treatments, or lines of therapy. This study explored the association between objective response (OR) and OS in patients with chemotherapy-refractory metastatic Merkel cell carcinoma who received avelumab (anti-PD-L1). METHODS: Eighty-eight patients enrolled in JAVELIN Merkel 200 (part A; NCT02155647) received i...
February 5, 2019: Cancer Immunology, Immunotherapy: CII
Amedeo Sciarra, Inês Monteiro, Christine Ménétrier-Caux, Christophe Caux, Benoit Gilbert, Nermin Halkic, Stefano La Rosa, Pedro Romero, Christine Sempoux, Laurence de Leval
The following information must be added to the published article.
February 5, 2019: Cancer Immunology, Immunotherapy: CII
David Agdashian, Mei ElGindi, Changqing Xie, Milan Sandhu, Drew Pratt, David E Kleiner, William D Figg, Julie A Rytlewski, Catherine Sanders, Erik C Yusko, Bradford Wood, David Venzon, Gagandeep Brar, Austin G Duffy, Tim F Greten, Firouzeh Korangy
BACKGROUND: Checkpoint inhibitors have recently been approved for the treatment of patients with hepatocellular carcinoma (HCC). However, biomarkers, which will help identify patients responding to therapy, are missing. We recently tested the combination of anti-CTLA4 treatment (tremelimumab) with loco-regional therapy in patients with HCC and reported a partial response rate of 26%. METHODS: Here, we report updated survival analyses and results from our immune monitoring studies on peripheral blood mononuclear cells (PBMCs) and tumors from these patients...
January 28, 2019: Cancer Immunology, Immunotherapy: CII
Luca Cassetta, Espen S Baekkevold, Sven Brandau, Anna Bujko, Marco A Cassatella, Anca Dorhoi, Carsten Krieg, Ang Lin, Karin Loré, Olivia Marini, Jeffrey W Pollard, Mikael Roussel, Patrizia Scapini, Viktor Umansky, Gosse J Adema
In cancer, infection and inflammation, the immune system's function can be dysregulated. Instead of fighting disease, immune cells may increase pathology and suppress host-protective immune responses. Myeloid cells show high plasticity and adapt to changing conditions and pathological challenges. Despite their relevance in disease pathophysiology, the identity, heterogeneity and biology of myeloid cells is still poorly understood. We will focus on phenotypical and functional markers of one of the key myeloid regulatory subtypes, the myeloid derived suppressor cells (MDSC), in humans, mice and non-human primates...
January 25, 2019: Cancer Immunology, Immunotherapy: CII
Ryungsa Kim, Ami Kawai, Megumi Wakisaka, Yuri Funaoka, Naomi Yasuda, Masayuki Hidaka, Yukitaka Morita, Shoichro Ohtani, Mitsuya Ito, Koji Arihiro
Tumor-infiltrating lymphocytes are an important prognostic factor after neoadjuvant chemotherapy (NAC) in patients with breast cancer. Natural killer (NK) cells play critical roles in antitumor immune surveillance. Here, we assessed the relationship between peripheral natural killer (pNK) cell activity, tumor microenvironmental factors (TMEFs), and the therapeutic efficacy of preoperative chemotherapy in patients with breast cancer. In a cohort of 39 patients diagnosed with stage II-IV breast cancer who received NAC, we measured pNK cell activity by chromium release assay and assessed TMEF levels by next-generation sequencing...
January 23, 2019: Cancer Immunology, Immunotherapy: CII
Julia Schollbach, Stefan Kircher, Armin Wiegering, Florian Seyfried, Ingo Klein, Andreas Rosenwald, Christoph-Thomas Germer, Stefan Löb
The prognostic value of the local immune phenotype in patients with colorectal cancer has been extensively studied. Neoadjuvant radiotherapy and/or chemotherapy may potentially influence these immune responses. In this study, we examined the prognostic role of indoleamine-2,3-Dioxygenase (IDO1) and infiltrating cytotoxic T lymphocytes (CD8+) in locally advanced rectal carcinomas after neoadjuvant treatment. Expression of IDO1 and CD8 was evaluated by immunohistochemistry in 106 archival tumour tissue samples from patients following neoadjuvant chemoradiation and radical resection...
January 22, 2019: Cancer Immunology, Immunotherapy: CII
Hamzah Abu-Sbeih, Faisal S Ali, Wei Qiao, Yang Lu, Sapna Patel, Adi Diab, Yinghong Wang
BACKGROUND: Gastrointestinal (GI) immune-related adverse events (irAEs) commonly limit immune checkpoint inhibitors' (ICIs) treatment, which is very effective for metastatic melanoma. The independent impact of GI-irAEs on patients' survival is not well studied. We aimed to assess the impact of GI-irAEs on survival rates of patients with metastatic melanoma using multivariate model. METHODS: This is a retrospective study of patients with metastatic melanoma who developed GI-irAEs from 1/2010 through 4/2018...
January 21, 2019: Cancer Immunology, Immunotherapy: CII
Vaianu Leroy, Emilie Gerard, Caroline Dutriaux, Sorilla Prey, Aurelia Gey, Cécile Mertens, Marie Beylot-Barry, Anne Pham-Ledard
BACKGROUND: Checkpoint inhibitors are first-line therapies in melanoma, but safety in older adults has not yet been assessed. Ipilimumab improves survival, but immunologic-related adverse events (AEs) can be threatening, and its use in elderly people raises questions. AIM: To assess safety in a cohort of very elderly patients treated with ipilimumab. METHODS: All patients over 80 years treated with ipilimumab for melanoma were retrospectively included...
January 19, 2019: Cancer Immunology, Immunotherapy: CII
Elodie Pliquet, Claude Ruffie, Marie Escande, Jessie Thalmensi, Valérie Najburg, Chantal Combredet, Thomas Bestetti, Marion Julithe, Christelle Liard, Thierry Huet, Simon Wain-Hobson, Frédéric Tangy, Pierre Langlade-Demoyen
Cancer immunotherapy is seeing an increasing focus on vaccination with tumor-associated antigens (TAAs). Human telomerase (hTERT) is a TAA expressed by most tumors to overcome telomere shortening. Tolerance to hTERT can be easily broken both naturally and experimentally and hTERT DNA vaccine candidates have been introduced in clinical trials. DNA prime/boost strategies have been widely developed to immunize efficiently against infectious diseases. We explored the use of a recombinant measles virus (MV) hTERT vector to boost DNA priming as recombinant live attenuated measles virus has an impressive safety and efficacy record...
January 17, 2019: Cancer Immunology, Immunotherapy: CII
Charlotte M Huijts, Sinéad M Lougheed, Zuhir Bodalal, Carla M van Herpen, Paul Hamberg, Metin Tascilar, John B Haanen, Henk M Verheul, Tanja D de Gruijl, Hans J van der Vliet
For the treatment of metastatic renal cell cancer several strategies are used among which the mTOR inhibitor everolimus. As mTOR plays an important role in the immune system, e.g., by controlling the expression of the transcription factor FoxP3 thereby regulating regulatory T cells (Tregs), it plays a key role in the balance between tolerance and inflammation. Previous reports showed stimulatory effects of mTOR inhibition on the expansion of Tregs, an effect that can be considered detrimental in terms of cancer control...
January 17, 2019: Cancer Immunology, Immunotherapy: CII
Morten Nørgaard Andersen, Anders Etzerodt, Jonas H Graversen, Lisa C Holthof, Søren K Moestrup, Marianne Hokland, Holger J Møller
Tumor-associated macrophages (TAMs) are of major importance in cancer-related immune suppression, and tumor infiltration by CD163pos TAMs is associated with poor outcome in most human cancers. Therefore, therapeutic strategies for reprogramming TAMs from a tumor-supporting (M2-like) phenotype towards a tumoricidal (M1-like) phenotype are of great interest. Activation of the transcription factor STAT3 within the tumor microenvironment is associated with worse prognosis, and STAT3 activation promotes the immunosuppressive phenotype of TAMs...
January 14, 2019: Cancer Immunology, Immunotherapy: CII
Anna Malyshkina, Elisabeth Littwitz-Salomon, Kathrin Sutter, Jean Alexander Ross, Annette Paschen, Sonja Windmann, Simone Schimmer, Ulf Dittmer
T cell responses are crucial for anti-tumor immunity. In chronic viral infections, anti-tumor T cell responses can be compromised due to various immunological mechanisms, including T cell exhaustion. To study mechanisms of anti-tumor immunity during a chronic viral infection, we made use of the well-established Friend virus (FV) mouse model. Chronically FV-infected mice are impaired in their ability to reject FBL-3 cells-a virus-induced tumor cell line of C57BL/6 origin. Here we aimed to explore therapeutic strategies to overcome the influence of T cell exhaustion during chronic viral infection, and reactivate effector CD8+ and CD4+ T cells to eliminate tumor cells...
January 11, 2019: Cancer Immunology, Immunotherapy: CII
Amedeo Sciarra, Inês Monteiro, Christine Ménétrier-Caux, Christophe Caux, Benoit Gilbert, Nermin Halkic, Stefano La Rosa, Pedro Romero, Christine Sempoux, Laurence de Leval
BACKGROUND: The tumor-expressed CD73 ectonucleotidase generates immune tolerance and promotes invasiveness via adenosine production from degradation of AMP. While anti-CD73 blockade treatment is a promising tool in cancer immunotherapy, a characterization of CD73 expression in human hepatobiliopancreatic system is lacking. PATIENTS AND METHODS: CD73 expression was investigated by immunohistochemistry in a variety of non-neoplastic and neoplastic conditions of the liver, pancreas, and biliary tract...
January 4, 2019: Cancer Immunology, Immunotherapy: CII
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