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PD1 cancer

Jifu E, Feihu Yan, Zhengchun Kang, Liangliang Zhu, Junjie Xing, Enda Yu
Tumor-draining lymph nodes (TDLNs) are the primary sites of tumor antigen presentation, as well as the origin of metastasis in most cases. Hence, the type and function of immune cells in TDLNs are critical to the microenvironment and potentially affect the clinical outcome of the malignancy. CD8+ CXCR5+ T cells are recently described to present high effector functions in infectious diseases, but their role in colorectal cancer (CRC) remains unclear. In forty-four Stage III CRC patients, we examined the CD8+ CXCR5+ T cells in blood, tumor, and TDLN...
March 12, 2018: Human Immunology
Franz L Ricklefs, Quazim Alayo, Harald Krenzlin, Ahmad B Mahmoud, Maria C Speranza, Hiroshi Nakashima, Josie L Hayes, Kyungheon Lee, Leonora Balaj, Carmela Passaro, Arun K Rooj, Susanne Krasemann, Bob S Carter, Clark C Chen, Tyler Steed, Jeffrey Treiber, Scott Rodig, Katherine Yang, Ichiro Nakano, Hakho Lee, Ralph Weissleder, Xandra O Breakefield, Jakub Godlewski, Manfred Westphal, Katrin Lamszus, Gordon J Freeman, Agnieszka Bronisz, Sean E Lawler, E Antonio Chiocca
Binding of programmed death ligand-1 (PD-L1) to programmed cell death protein-1 (PD1) leads to cancer immune evasion via inhibition of T cell function. One of the defining characteristics of glioblastoma, a universally fatal brain cancer, is its profound local and systemic immunosuppression. Glioblastoma has also been shown to generate extracellular vesicles (EVs), which may play an important role in tumor progression. We thus hypothesized that glioblastoma EVs may be important mediators of immunosuppression and that PD-L1 could play a role...
March 2018: Science Advances
Maria Rita Gaiser, Nikolas von Bubnoff, Christoffer Gebhardt, Jochen Sven Utikal
During the last six years, several innovative, systemic therapies for the treatment of metastatic malignant melanoma (MM) have emerged. Conventional chemotherapy has been superseded by novel first-line therapies, including systemic immunotherapies (anti-CTLA4 and anti-PD1; authorization of anti-PDL1 is anticipated) and therapies targeting specific mutations (BRAF, NRAS, and c-KIT). Thus, treating physicians are confronted with new challenges, such as stratifying patients for appropriate treatments and monitoring long-term responders for progression...
March 7, 2018: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
Jessica Moskovitz, Jennifer Moy, Robert L Ferris
PURPOSE OF REVIEW: Discussion of current strategies targeting the immune system related to solid tumors with emphasis on head and neck squamous cell carcinoma (HNSCC).This review will outline the current challenges with immunotherapy and future goals for treatment using these agents. RECENT FINDINGS: Agents targeting immune checkpoint receptors (IR) such as program death 1 (PD1) have been used in the clinical realm for melanoma and non-small cell lung cancer (NSCLC), and the use of these agents for these malignancies has provided crucial information about how and why patients respond or not to inhibitory checkpoint receptor blockade therapy (ICR)...
March 3, 2018: Current Oncology Reports
Jakob Nikolas Kather, Niels Halama, Dirk Jaeger
Colorectal cancer (CRC) is a common and lethal disease with a high therapeutic need. For most patients with metastatic CRC, chemotherapy is the only viable option. Currently, immunotherapy is restricted to the particular genetic subgroup of mismatch-repair deficient (MMRd)/microsatellite instable (MSI) CRC. Anti-PD1 therapy was recently FDA-approved as a second-line treatment in this subgroup. However, in a metastatic setting, these MMRd/MSI tumors are vastly outnumbered by mismatch-repair proficient (MMRp)/microsatellite stable (MSS) tumors...
March 1, 2018: Seminars in Cancer Biology
Erik Ladomersky, Lijie Zhai, Alicia Lenzen, Kristen L Lauing, Jun Qian, Denise M Scholtens, Galina Gritsina, Xuebing Sun, Ye Liu, Fenglong Yu, Wenfeng Gong, Yong Liu, Beibei Jiang, Zhiyu Tang, Ricky Patel, Leonidas C Platanias, C David James, Roger Stupp, Rimas V Lukas, David C Binder, Derek A Wainwright
PURPOSE: Glioblastoma (GBM) is the most aggressive primary brain tumor in adults with a median survival of 15-20 months. Numerous approaches and novel therapeutics for treating GBM have been investigated in the setting of phase III clinical trials, including a recent analysis of the immune checkpoint inhibitor, Nivolumab (anti-PD-1), which failed to improve recurrent GBM patient survival. However, rather than abandoning immune checkpoint inhibitor treatment for GBM, which has shown promise in other types of cancer, ongoing studies are currently evaluating this therapeutic class when combined with other agents...
March 2, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Yanxia Guo, Alice M Walsh, Mary Canavan, Mihir D Wechalekar, Suzanne Cole, Xuefeng Yin, Brittney Scott, Mathew Loza, Carl Orr, Trudy McGarry, Michele Bombardieri, Frances Humby, Susanna M Proudman, Costantino Pitzalis, Malcolm D Smith, Joshua R Friedman, Ian Anderson, Loui Madakamutil, Douglas J Veale, Ursula Fearon, Sunil Nagpal
Immune checkpoint blockade with therapeutic anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 (Ipilimumab) and anti-programmed death (PD)-1 (Nivolumab and Pembrolizumab) antibodies alone or in combination has shown remarkable efficacy in multiple cancer types, concomitant with immune-related adverse events, including arthralgia and inflammatory arthritis (IA) in some patients. Herein, using Nivolumab (anti-PD-1 antagonist)-responsive genes along with transcriptomics of synovial tissue from multiple stages of rheumatoid arthritis (RA) disease progression, we have interrogated the activity status of PD-1 pathway during RA development...
2018: PloS One
Jooeun Bae, Teru Hideshima, Yu-Tzu Tai, Yan Song, Paul Richardson, Noopur Raje, Nikhil C Munshi, Kenneth C Anderson
Histone deacetylases (HDAC) are therapeutic targets in multiple cancers. ACY241, an HDAC6 selective inhibitor, has shown anti-multiple myeloma (MM) activity in combination with immunomodulatory drugs and proteasome inhibitors. Here we show ACY241 significantly reduces the frequency of CD138+ MM cells, CD4+ CD25+ FoxP3+ regulatory T cells, and HLA-DRLow/- CD11b+ CD33+ myeloid-derived suppressor cells; and decreases expression of PD1/PD-L1 on CD8+ T cells and of immune checkpoints in bone marrow cells from myeloma patients...
February 22, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Arnaud Jannin, Emilie Merlen, Christine Do Cao, Nicolas Penel
Recently developed immunotherapeutic agents, like anti-cytotoxic T lymphocyte antigen 4 antibody (CTLA4), anti-programmed cell death 1 (PD1) or anti-programmed cell death-ligand 1 (PDL1), have demonstrated substantial potential for the treatment of a variety of malignancies. Autoimmune side effects from these agents are diverse and can include multiple endocrinopathies like immunotherapy induced hypophysitis (IH). These toxicities appear to be more frequent in patients receiving anti-CTLA4 antibody compared to PD1/PDL1 agents...
February 20, 2018: Bulletin du Cancer
Manish R Patel
Immune therapy has now been incorporated into the standard of care for non-small-cell lung cancer based on randomized trials showing superiority of anti-PD1 antibodies compared with chemotherapy. Thus there is a renewed interest in immune approaches to treating lung cancer. One promising approach is with oncolytic viruses that either naturally or through engineering, preferentially infect or kill cancer cells. In preclinical models of different thoracic cancers, it has been found that these viruses can induce immune responses through multiple mechanisms...
April 2018: Immunotherapy
Marta Elosua-González, Ana Pampín-Franco, Ramón Mazzucchelli-Esteban, Xabier Mielgo-Rubio, Ximena Rodriguez-Vásquez, Elena García-Zamora, Jose Luis López-Estebaranz
Nivolumab, a monoclonal antibody against the programmed cell death protein 1 (PD-1), has shown promising results in patients with advanced malignancies, including melanoma, lung cancer, and renal cancer. Immune-related adverse events (irAEs) have been reported, including both organ-specific toxicities and skin toxicities. Herein, we report a case of predominantly palmoplantar psoriasis with severe nail involvement, psoriatic arthritis, and autoimmune hypothyroidism after receiving nivolumab treatment for lung cancer...
August 15, 2017: Dermatology Online Journal
Ichiyo Shibahara, Mitsuto Hanihara, Takashi Watanabe, Mitsuru Dan, Sumito Sato, Hiroki Kuroda, Akinori Inamura, Madoka Inukai, Atsuko Hara, Yoshie Yasui, Toshihiro Kumabe
Biomaterials to treat cancers hold therapeutic potential; however, their translation to bedside treatment requires further study. The carmustine (1,3-bis (2-chloroethyl)-1-nitrosourea; BCNU) wafer, a biodegradable polymer, currently is the only drug that is able to be placed at the surgical site to treat malignant tumors. However, how this wafer affects the surrounding tumor microenvironment is not well understood to date. We retrospectively reviewed all patients with glioblastoma treated with and without BCNU wafers who underwent repeat resection at tumor recurrence...
February 21, 2018: Journal of Neuro-oncology
Purnima Bhat, Anne-Sophie Bergot, Nigel Waterhouse, Ian Hector Frazer
Cervical cancer is a malignant transformation of keratinocytes initiated by the E7 oncoprotein of human papillomavirus (HPV). These tumors are characterized by keratinocyte hyperproliferation and are often infiltrated with activated CD8 T cells. HPV infection confers changes to gain immunological advantage to promote chronic infection, and these persist with malignant transformation. We investigated the relative importance of the many redundant mechanisms of cytotoxicity used by CD8 T cells to kill keratinocytes expressing HPV E7 oncoprotein using extended-duration time-lapse microscopy that allows examination of cell-to-cell interactions during killing...
January 19, 2018: Oncotarget
Shiraj Sen, Kenneth Hess, David S Hong, Aung Naing, Sarina Piha-Paul, Filip Janku, Siqing Fu, Ishwaria M Subbiah, Holly Liu, Rahil Khanji, Le Huang, Shhyam Moorthy, Daniel D Karp, Apostolia Tsimberidou, Funda Meric-Bernstam, Vivek Subbiah
BACKGROUND: We sought to develop a prognostic scoring system to aid in patient selection for immune checkpoint inhibitor (ICI) phase 1 clinical trials. METHODS: Clinical data from patients treated in phase 1 ICI clinical trials at MD Anderson (MDA) Center were analysed. Seventeen clinical factors were studied. Recursive partitioning analysis, a tree-based model, was used to develop a regression tree and identify optimal cut-points based on differences in survival for each clinical factor...
February 20, 2018: British Journal of Cancer
San-Chi Chen, Peter Mu-Hsin Chang, Hsiao-Jung Wang, Shyh-Kuan Tai, Pen-Yuan Chu, Muh-Hwa Yang
PD-L1 expression is critical in helping tumor cells evade the immune system. However, the level of PD-L1 expression in non-oropharyngeal head and neck squamous cell carcinoma (non-OPHNSCC) and its association with patient prognosis remains unclear. A retrospective clinicopathological analysis was performed on 106 patients with non-OPHNSCC diagnosed between 2007 and 2014. In the current study, tissue arrays from paraffin-embedded non-OPHNSCC samples obtained from patients were constructed, and PD-L1 and p16 INK4A expression were determined using immunohistochemistry...
February 2018: Oncology Letters
Patrick Lee, Shashi Gujar
The clinical effectiveness of immunotherapies for prostate cancer remains subpar compared with that for other cancers. The goal of most immunotherapies is the activation of immune effectors, such as T cells and natural killer cells, as the presence of these activated mediators positively correlates with patient outcomes. Clinical evidence shows that prostate cancer is immunogenic, accessible to the immune system, and can be targeted by antitumour immune responses. However, owing to the detrimental effects of prostate-cancer-associated immunosuppression, even the newest immunotherapeutic approaches fail to initiate the clinically desired antitumour immune reaction...
February 13, 2018: Nature Reviews. Urology
Salvatore Alfieri, Stefano Cavalieri, Lisa Licitra
PURPOSE OF REVIEW: In the last decade, after cetuximab (anti-epidermal growth factor receptor), none of the novel investigated compounds has demonstrated benefit in head and neck squamous cell cancers (HNSCC), both in advanced and curative settings. Therefore, prognosis of recurrent/metastatic (R/M) HNSCC patients remains dismal, especially in platinum-refractory cohort. In the last few years, a new important class of drugs has affirmed its role. HNSCC, even if less 'immunogenic' than other malignancies (e...
April 2018: Current Opinion in Otolaryngology & Head and Neck Surgery
Paul Zolkind, Dariusz Przybylski, Nemanja Marjanovic, Lan Nguyen, Tianxiang Lin, Tanner Johanns, Anton Alexandrov, Liye Zhou, Clint T Allen, Alexander P Miceli, Robert D Schreiber, Maxim Artyomov, Gavin P Dunn, Ravindra Uppaluri
Head and neck squamous cell carcinomas (HNSCC) are an ideal immunotherapy target due to their high mutation burden and frequent infiltration with lymphocytes. Preclinical models to investigate targeted and combination therapies as well as defining biomarkers to guide treatment represent an important need in the field. Immunogenomics approaches have illuminated the role of mutation-derived tumor neoantigens as potential biomarkers of response to checkpoint blockade as well as representing therapeutic vaccines...
January 9, 2018: Oncotarget
Ho Liam Pock, Teo Yi Wei Bryan, Tan Puay Hoon, Jabed Iqbal, Linn Yeh Ching, Goh Yeow Tee, Tan Kar Wai, Toh Han Chong, Ong Kong Wee, Yeoh Kheng Wei
AIM: The new radioimmunotherapeutic regime GAP15R aims to stimulate glucocorticoid-induced TNF-related protein (G) to overcome Treg suppression; add IFN-α (A) to promote inflammatory milieu; block PD1 (P) to disinhibit T effector cytotoxicity; add IL-15 (15) to enhance danger signals & T-cell expansion; and apply radiation (R) at critical time point to sustain localized inflammation. Patients & methods/materials & methods: This was tested in a murine 4T1 metastatic breast carcinoma model given GAP15R with regular monitoring of tumor volume and complications...
February 1, 2018: Immunotherapy
Kyriaki Papadopoulou, Samuel Murray, Kyriaki Manousou, Ioannis Tikas, Christos Dervenis, Joseph Sgouros, Dimitra Rontogianni, Sotirios Lakis, Mattheos Bobos, Christos Poulios, Stavroula Pervana, Georgios Lazaridis, George Fountzilas, Vassiliki Kotoula
Biliary tract cancer (BTC) represents a heterogeneous disease with dismal outcome. Herein, we examined genotype and angiogenesis features in BTC. We applied genotyping (Sanger, qPCR, 101-gene panel NGS), mRNA relative quantification methods, and β-catenin immunohistochemistry in 84 FFPE BTC (55 gallbladder [GBC], 14 intrahepatic [ICC], 15 extrahepatic [ECC] carcinomas). We identified 541 mutations in 68 (81%) tumors. Top mutated genes were CTNNB1 (36%); PTEN (33%); TP53 (31%); PIK3R1 (29%); PIK3CA (13%); BRCA2 and KRAS (12%); BRCA1 (11%)...
2018: American Journal of Cancer Research
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