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https://www.readbyqxmd.com/read/29326088/age-effects-of-distinct-immune-checkpoint-blockade-treatments-in-a-mouse-melanoma-model
#1
Álvaro Padrón, Vincent Hurez, Harshita B Gupta, Curtis A Clark, Sri Lakshmi Pandeswara, Bin Yuan, Robert S Svatek, Mary Jo Turk, Justin M Drerup, Rong Li, Tyler J Curiel
Cancer immunotherapy has shown remarkable recent progress. Immune checkpoint blocking antibodies have become the most successful anti-cancer agent class ever developed, with six distinct agents approved since 2011 for a wide variety of cancers. Although age is the biggest risk factor for cancer (aside from selected early-onset pediatric cancers), these agents were tested pre-clinically in young hosts, and there is remarkably little published on the effects of host age on treatment outcomes in pre-clinical studies or human clinical trials...
January 8, 2018: Experimental Gerontology
https://www.readbyqxmd.com/read/29305257/the-expression-of-mctla-4-in-skin-lesion-inversely-correlates-with-the-severity-of-psoriasis
#2
Panpan Liu, Yijing He, Honglin Wang, Yehong Kuang, Wangqing Chen, Jie Li, Mingliang Chen, Jianglin Zhang, Juan Su, Shuang Zhao, Menglin Chen, Juan Tao, Xiang Chen, Wu Zhu
BACKGROUND: Psoriasis is a chronic inflammatory disease characterized by epidermal hyperplasia and increased T cell infiltration. Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a key factor that affects T cell function and immune response. However, whether the expression of CTLA-4 affects the severity of psoriasis is still unknown. OBJECTIVE: The aim of the project was to investigate the correlation between the expression of CTLA-4 and the severity of psoriasis. METHODS: The plasma soluble CTLA-4 levels and membrane CTLA-4 expression were measured by enzyme-linked immunosorbent assay and immunohistochemistry analysis in mild, moderate and severe psoriasis patients, respectively...
November 22, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29303289/-small-cell-lung-cancer-epidemiology-diagnostics-and-therapy
#3
Miloš Pešek, Jan Mužík
Authors present actual overview of information on diagnostic and therapeutic procedures in small-cell lung cancer (SCLC). This highly aggressive type of lung cancer is diagnosed in 14.8 % of Czech lung cancer patients. Vast majority of those patients (87 %) suffer from advanced and metastatic disease in the time of diagnosis. In this issue are presented prognostic factors, staging diagnostic procedures and therapeutic recommendations. The backbone of actual SCLC treatment is combined chemotherapy and radiotherapy and less frequently, carefully in selected cases, surgical procedures...
2018: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/29301960/genomic-correlates-of-response-to-immune-checkpoint-therapies-in-clear-cell-renal-cell-carcinoma
#4
Diana Miao, Claire A Margolis, Wenhua Gao, Martin H Voss, Wei Li, Dylan J Martini, Craig Norton, Dominick Bossé, Stephanie M Wankowicz, Dana Cullen, Christine Horak, Megan Wind-Rotolo, Adam Tracy, Marios Giannakis, Frank Stephen Hodi, Charles G Drake, Mark W Ball, Mohamad E Allaf, Alexandra Snyder, Matthew D Hellmann, Thai Ho, Robert J Motzer, Sabina Signoretti, William G Kaelin, Toni K Choueiri, Eliezer M Van Allen
Immune checkpoint inhibitors targeting the programmed cell death-1 receptor (PD-1) improve survival in a subset of patients with clear cell renal cell carcinoma (ccRCC). To identify genomic alterations in ccRCC that correlate with response to anti-PD-1 monotherapy, we performed whole exome sequencing of metastatic ccRCC from 35 patients. We found that clinical benefit was associated with loss-of-function mutations in the PBRM1 gene (p=0.012), which encodes a subunit of a SWI/SNF chromatin remodeling complex (the PBAF subtype)...
January 4, 2018: Science
https://www.readbyqxmd.com/read/29296965/infiltration-of-effector-regulatory-t-cells-predicts-poor-prognosis-of-diffuse-large-b-cell-lymphoma-not-otherwise-specified
#5
Shoko Nakayama, Taiji Yokote, Toshikazu Akioka, Nobuya Hiraoka, Uta Nishiwaki, Takuji Miyoshi, Kazuki Iwaki, Ayami Takayama, Yuki Masuda, Jun Hatooka, Mayumi Fujimoto, Yasuichiro Nishimura, Motomu Tsuji
Regulatory T cells (Tregs) specifically express the transcription factor forkhead box P3 (FOXP3) and contribute to tumor progression. FOXP3-positive cells have been recently proven to be heterogeneous in phenotype and function, including effector Tregs (eTregs), naïve Tregs, and non-Tregs, which harbor no suppressive function. Therefore, it is crucial to investigate the "true Treg (eTreg)" population, rather than the entire FOXP3 population, with regards to their effect on tumor immunity. In particular, in diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), FOXP3-positive cells correlated with a better prognosis...
March 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/29278210/biologics-in-inflammatory-and-immunomediated-arthritis
#6
Michele Maria Luchetti, Devis Benfaremo, Armando Gabrielli
BACKGROUND: Biologic drugs, introduced in clinical practice almost twenty years ago, represent nowadays a prominent treatment option in patients with chronic inflammatory arthritis, such as Rheumatoid Arthritis, Psoriatic Arthritis and Spondyloarthritis, that include ankylosing spondylitis and non-radiographic axial spondyloarthritis. METHODS: Several compounds targeting different pathways have been marketed and approved for the treatment of inflammatory arthritis, with a significant impact on the clinical outcomes and the natural history of the diseases...
December 26, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/29275461/tumor-immuno-environment-in-cancer-progression-and-therapy
#7
Pawel Kalinski, James E Talmadge
The approvals of Provenge (Sipuleucel-T), Ipilimumab (Yervoy/anti-CTLA-4) and blockers of the PD-1 - PD-L1/PD-L2 pathway, such as nivolumab (Opdivo), pembrolizumab (Keytruda), or atezolizumab (Tecentriq), have established immunotherapy as a key component of comprehensive cancer care. Further, murine mechanistic studies and studies in immunocompromised patients have documented the critical role of immunity in effectiveness of radio- and chemotherapy. However, in addition to the ability of the immune system to control cancer progression, it can also promote tumor growth, via regulatory T cells (Tregs), myeloid-derived dendritic cells (MDSCs) and tumor associated macrophages (TAM), which can enhance survival of cancer cells directly or via the regulation of the tumor stroma...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29258739/combination-immunotherapy-of-muc1-mrna-nano-vaccine-and-ctla-4-blockade-effectively-inhibits-growth-of-triple-negative-breast-cancer
#8
Lina Liu, Yuhua Wang, Lei Miao, Qi Liu, Sara Musetti, Jun Li, Leaf Huang
Triple negative breast cancer (TNBC), which constitutes 10%-20% of all breast cancers, is associated with aggressive progression, a high rate of metastasis, and poor prognosis. The treatment of patients with TNBC remains a great clinical challenge. Preclinical reports support the combination immunotherapy of cancer vaccines and immune checkpoint blockades in non-immunogenic tumors. In this study, we constructed nanoparticles (NPs) to deliver an mRNA vaccine encoding tumor antigen MUC1 to dendritic cells (DCs) in lymph nodes to activate and expand tumor-specific T cells...
December 5, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29245905/the-sexist-behaviour-of-immune-checkpoint-inhibitors-in-cancer-therapy
#9
Andrea Botticelli, Concetta Elisa Onesti, Ilaria Zizzari, Bruna Cerbelli, Paolo Sciattella, Mario Occhipinti, Michela Roberto, Francesca Di Pietro, Adriana Bonifacino, Michele Ghidini, Patrizia Vici, Laura Pizzuti, Chiara Napoletano, Lidia Strigari, Giulia D'Amati, Federica Mazzuca, Marianna Nuti, Paolo Marchetti
Background: Immune checkpoint inhibitors, targeting the molecules CTLA-4, PD-1 and PD-L1, showed efficacy against several type of cancers and are currently used in clinical practice. An important biological variable that influences innate and adaptive immunity is the sex, acting through genetic, hormonal and environmental factors. The overall differences between sexes could be crucial to evaluate the response to ICIs. Materials and methods: We performed a meta-analysis of Phase II-III Clinical Trials published up to June 2017 in which anti-CTLA-4, anti-PD-1 and anti-PD-L1 were studied...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29239194/-immunotherapy-of-renal-cell-carcinoma
#10
A Poprach, R Lakomý, T Büchler
Treatment of renal cell carcinoma is still palliative. Targeted therapy increases response rates and prolongs overall survival and progression-free survival compared with cytokines and chemotherapy. Checkpoint inhibitors constitute the up-date of therapeutic approaches, and anti-PD-1 antibody, one checkpoint inhibitor, is now well established as a second and/or third palliative treatment for patients with renal cell carcinoma. In this study, we present the latest data from current studies on cytokines, cancer vaccines, ipilimumab, and nivolumab...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/29238906/thyroid-dysfunctions-secondary-to-cancer-immunotherapy
#11
REVIEW
P Chalan, G Di Dalmazi, F Pani, A De Remigis, A Corsello, P Caturegli
BACKGROUND: Immunotherapy is a firmly established pillar in the treatment of cancer, alongside the traditional approaches of surgery, radiotherapy, and chemotherapy. Like every treatment, also cancer immunotherapy causes a diverse spectrum of side effects, collectively referred to as immune-related adverse events. OBJECTIVE: This review will examine the main forms of immunotherapy, the proposed mechanism(s) of action, and the incidence of thyroid dysfunctions. METHODS: A comprehensive MEDLINE search was performed for articles published up to March 30, 2017...
December 13, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/29237802/phase-1-dose-escalation-study-of-anti-ctla-4-antibody-ipilimumab-and-lenalidomide-in-patients-with-advanced-cancers
#12
Divya Sakamuri, Isabella C Glitza, Sonia L Betancourt Cuellar, Vivek Subbiah, Siqing Fu, Apostolia M Tsimberidou, Jennifer J Wheler, David S Hong, Aung Naing, Gerald S Falchook, Michelle A Fanale, Maria E Cabanillas, Filip Janku
Preclinical data suggest that combining a check point inhibition with immunomodulatory derivative can increase anticancer response. We designed a dose escalation study using a 3+3 design to determine the safety, maximum tolerated dose (MTD) or recommended phase 2 dose (R2PD) and dose limiting toxicities (DLT) of the anti-CTLA-4 antibody ipilimumab (1.5-3mg/kg intravenously every 28 days x 4) and lenalidomide (10-25mg orally daily for 21 of 28 days until disease progression or unacceptable toxicity) in advanced cancers...
December 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29217585/patient-hla-class-i-genotype-influences-cancer-response-to-checkpoint-blockade-immunotherapy
#13
Diego Chowell, Luc G T Morris, Claud M Grigg, Jeffrey K Weber, Robert M Samstein, Vladimir Makarov, Fengshen Kuo, Sviatoslav M Kendall, David Requena, Nadeem Riaz, Benjamin Greenbaum, James Carroll, Edward Garon, David M Hyman, Ahmet Zehir, David Solit, Michael Berger, Ruhong Zhou, Naiyer A Rizvi, Timothy A Chan
CD8+ T cell-dependent killing of cancer cells requires efficient presentation of tumor antigens by human leukocyte antigen class I (HLA-I) molecules. However, the extent to which patient-specific HLA-I genotype influences response to anti-PD-1 or anti-CTLA-4 is currently unknown. We determined the HLA-I genotype of 1,535 advanced cancer patients treated with immune checkpoint blockade (ICB). Maximal heterozygosity at HLA-I loci (A, B, and C) improved overall survival after ICB compared to patients who were homozygous for at least one HLA locus...
December 7, 2017: Science
https://www.readbyqxmd.com/read/29213157/immunotherapy-and-gene-therapy-as-novel-treatments-for-cancer
#14
REVIEW
Martha Montserrat Rangel-Sosa, Estuardo Aguilar-Córdova, Augusto Rojas-Martínez
The immune system interacts closely with tumors during the disease development and progression to metastasis. The complex communication between the immune system and the tumor cells can prevent or promote tumor growth. New therapeutic approaches harnessing protective immunological mechanisms have recently shown very promising results. This is performed by blocking inhibitory signals or by activating immunological effector cells directly. Immune checkpoint blockade with monoclonal antibodies directed against the inhibitory immune receptors CTLA-4 and PD-1 has emerged as a successful treatment approach for patients with advanced melanoma...
September 30, 2017: Colombia Médica: CM
https://www.readbyqxmd.com/read/29207143/screening-and-antitumor-effect-of-an-anti%C3%A2-ctla%C3%A2-4-nanobody
#15
Ruirong Wan, Aiqun Liu, Xiaoqiong Hou, Zongqiang Lai, Jieping Li, Nuo Yang, Juntao Tan, Fengzhen Mo, Zixi Hu, Xiaomei Yang, Yongxiang Zhao, Xiaoling Lu
Cytotoxic T‑lymphocyte antigen‑4 (CTLA‑4) is a critical negative regulator of immune responses. CTLA‑4 is rapidly upregulated following T‑cell activation, and then binds to B7 molecules with a higher affinity than CD28. CTLA‑4 may abolish the initiation of the responses of T cells by raising the threshold of signals required for full activation of T cells, and it also may terminate ongoing T-cell responses. This regulatory role has led to the development of monoclonal antibodies (mAbs) designed to block CTLA‑4 activity for enhancing immune responses against cancer...
December 4, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29204524/distant-intracranial-failure-in-melanoma-brain-metastases-treated-with-stereotactic-radiosurgery-in-the-era-of-immunotherapy-and-targeted-agents
#16
Sahaja Acharya, Mustafaa Mahmood, Daniel Mullen, Deshan Yang, Christina I Tsien, Jiayi Huang, Stephanie M Perkins, Keith Rich, Michael Chicoine, Eric Leuthardt, Joshua Dowling, Gavin Dunn, Jesse Keller, Clifford G Robinson, Christopher Abraham
Purpose: Stereotactic radiosurgery (SRS) in combination with immunotherapy (IMT) or targeted therapy is increasingly being used in the setting of melanoma brain metastases (MBMs). The synergistic properties of combination therapy are not well understood. We compared the distant intracranial failure rates of intact MBMs treated with SRS, SRS + IMT, and SRS + targeted therapy. Methods and materials: Combination therapy was defined as delivery of SRS within 3 months of IMT (anti-CTLA-4 /anti-PD-1 therapy) or targeted therapy (BRAF/MEK inhibitors)...
October 2017: Advances in Radiation Oncology
https://www.readbyqxmd.com/read/29203894/combining-intratumoral-treg-depletion-with-androgen-deprivation-therapy-adt-preclinical-activity-in-the-myc-cap-model
#17
Ying-Chun Shen, Ali Ghasemzadeh, Christina M Kochel, Thomas R Nirschl, Brian J Francica, Zoila A Lopez-Bujanda, Maria A Carrera Haro, Ada Tam, Robert A Anders, Mark J Selby, Alan J Korman, Charles G Drake
BACKGROUND: Immune checkpoint blockade has shown promising antitumor activity against a variety of tumor types. However, responses in castration-resistant prostate cancer remain relatively rare-potentially due to low baseline levels of infiltration. Using an immunocompetent cMyc-driven model (Myc-CaP), we sought to understand the immune infiltrate induced by androgen deprivation therapy (ADT) and to leverage that infiltration toward therapeutic benefit. METHODS: Using flow cytometry, qPCR and IHC, we quantified ADT-induced immune infiltration in terms of cell type and function...
December 4, 2017: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/29189388/cd11c-targeted-delivery-of-dna-to-dendritic-cells-leads-to-cgas-and-sting-dependent-maturation
#18
Marlene F Laursen, Esben Christensen, Laura L T Degn, Kasper Jønsson, Martin R Jakobsen, Ralf Agger, Emil Kofod-Olsen
Immunotherapeutic activation of tumor-specific T cells has proven to be an interesting approach in anticancer treatment. Particularly, anti-CTLA-4 and anti-PD-1/PD-L1 treatment looks promising, and conceivably, even better clinical results might be obtained if such treatment could be combined with boosting the existing tumor-specific T-cell response. One way to achieve this could be by increasing the level of maturation of dendritic cells locally and in the draining lymph nodes. When exposed to cancer cells, dendritic cells may spontaneously mature because of danger-associated molecular patterns derived from the tumor cells...
November 17, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29187493/braf-nras-and-c-kit-advanced-melanoma-clinico-pathological-features-targeted-therapy-strategies-and-survival
#19
Giovanni Ponti, Marco Manfredini, Stefano Greco, Giovanni Pellacani, Roberta Depenni, Aldo Tomasi, Monia Maccaferri, Stefano Cascinu
BACKGROUND/AIM: The mutational status of stage III and IV melanomas should be recognized in order to allow for targeted therapies. The aim of our study was the characterization of BRAF, NRAS and C-KIT melanoma patients, in order to define their optimal management. PATIENTS AND METHODS: Between 1991 and 2015, 63 mutated melanoma patients were treated and monitored during their diagnostic and therapeutic management at a single institution. RESULTS: BRAF-mutated melanoma patients were the most common, representing 70% of the study population, while NRAS- and C-KIT-mutated melanoma represented 19% and 11% respectively...
December 2017: Anticancer Research
https://www.readbyqxmd.com/read/29180896/checkpoint-blockade-in-solid-tumors-and-b-cell-malignancies-with-special-consideration-of-the-role-of-cd200
#20
REVIEW
Reginald M Gorczynski, Fang Zhu
In the ontogeny of a normal immune response, a series of checkpoints must be overcome to ensure that unwanted and/or harmful self-directed activation responses are avoided. Many of the molecules now known to be active in this overseeing of the evolving immune activation cascade, contributing inhibitory signals to dampen an overexuberant response, belong to the immunoglobulin supergene family. These include members of the CD28/CTLA-4:B7.1/B7.2 receptor/ligand family, PD-1 and PDL-1, CD200 and CD200R, and the more recently described V-domain immunoglobulin suppressor of T-cell activation and its ligand (VSIG-3/IGSF11)...
2017: Cancer Management and Research
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