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Tumor immunotherapy

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https://www.readbyqxmd.com/read/28734176/cancer-immunotherapy-moving-forward-with-peptide-t-cell-vaccines
#1
REVIEW
Takumi Kumai, Aaron Fan, Yasuaki Harabuchi, Esteban Celis
Recent advances in cancer immunology, such as the discovery of immune checkpoint inhibitors, have validated immune cells as potential key players for effective cancer treatment. The efficacy of these therapies seems to be codependent on a tumor-reactive T lymphocyte response. For many years, numerous attempts and strategies in developing vaccines to generate tumor-reactive T cells have yielded poor results in the clinic due to suboptimal immunogenicity and the inability to overcome an immunosuppressive tumor microenvironment...
July 19, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28732279/turbocharging-vaccines-emerging-adjuvants-for-dendritic-cell-based-therapeutic-cancer-vaccines
#2
REVIEW
Mansi Saxena, Nina Bhardwaj
Development of therapeutic cancer vaccines has been hindered by the many pro-tumorigenic mechanisms at play in cancer patients that serve to suppress both antigen presenting cells and T cells. In face of these obstacles, cancer vaccines are most likely to promote anti-tumorigenic immune responses only when formulated with strong adjuvants, and in combination with new immune interventions designed to reverse immune suppression and exhaustion of T cells in the tumor microenvironment. Dendritic cells (DCs) are often termed 'nature's adjuvant' due to their exceptional capacity for initiating both innate and adaptive immune responses...
July 18, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28732118/pd-1-checkpoint-blockade-in-combination-with-an-mtor-inhibitor-restrains-hepatocellular-carcinoma-growth-induced-by-hepatoma-cell-intrinsic-pd-1
#3
Hui Li, Xiaoqiang Li, Shuang Liu, Lei Guo, Bo Zhang, Jubo Zhang, Qinghai Ye
Inhibitors of PD-1 administered as single agents have resulted in durable tumor regression in advanced cancer patients. However, only a minority of cancer patients respond to anti PD-1 immunotherapy. Here, we show that PD-1 expression in hepatocellular carcinoma (HCC) promotes tumor growth independently of adaptive immunity. Knockdown of PD-1 suppress tumor growth, whereas PD-1 overexpression enhances tumorigenesis in immunodeficient xenografted mice. Mechanistically, PD-1 binds the downstream mTOR effectors eukaryotic initiation factor 4E (eIF4E) and ribosomal protein S6 (S6), thus promoting their phosphorylation...
July 21, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28731944/cancer-immunotherapy-in-older-patients
#4
Kristen A Marrone, Patrick M Forde
Advancing age remains one of the most significant risk factors for cancer development. Changes in the immune system occur with aging, and likely play a role in the increased incidence of malignancy in older patients. With the advent of immune checkpoint inhibitors, and their use in a variety of malignancies, there has been an explosion of clinical trials evaluating their use. Unfortunately, these trials have not shown consistent results in elderly patients, nor have age-specific outcomes been consistently reported...
July 2017: Cancer Journal
https://www.readbyqxmd.com/read/28731046/pd-l1-expression-and-the-immune-microenvironment-in-primary-invasive-lobular-carcinomas-of-the-breast
#5
Elizabeth D Thompson, Janis M Taube, Rebecca J Asch-Kendrick, Aleksandra Ogurtsova, Haiying Xu, Rajni Sharma, Alan Meeker, Pedram Argani, Leisha A Emens, Ashley Cimino-Mathews
Tumor-infiltrating lymphocytes and immune checkpoint proteins such as PD-L1 are potential prognostic factors and therapeutic targets in breast cancer. Most studies characterizing the breast tumor immune microenvironment have focused on ductal carcinomas. Here we investigate the tumor microenvironment of primary invasive lobular carcinomas. Previously constructed tissue microarrays of 47 lobular carcinomas were labeled by immunohistochemistry for PD-L1, CD8, CD20, and FoxP3. The stromal immune infiltrate density was qualitatively scored as a percentage of tumor area: 1+ (<5%); 2+ (5-10%); 3+ (10-15%); or 4+ (>50%)...
July 21, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28730761/tumor-infiltrating-lymphocytes-as-a-prognostic-factor-in-malignant-melanoma-review-of-the-literature
#6
Vlad A Gata, Cosmin I Lisencu, Catalin I Vlad, Doina Piciu, Alexandru Irimie, Patriciu Achimas-Cadariu
Malignant melanoma represents the major cause of mortality among skin cancers, with increasing incidence and mortality rates worldwide. Despite the numerous public health campaigns and the efforts undertaken in the last decade regarding the establishment of a rapid diagnostic and an efficient treatment for these patients, the long-term prognosis has not been significantly improved. Thus, numerous studies were conducted in order to establish a more accurate prognosis, tumor infiltrating lymphocytes (TILs) being considered in many studies as independent prognostic factors of lymph node metastasis and overall survival in patients with melanoma...
May 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28730293/clinical-predictors-of-survival-in-patients-with-castration-resistant-prostate-cancer-receiving-sipuleucel-t-cellular-immunotherapy
#7
Mehmet Asim Bilen, Kenneth R Hess, Sumit K Subudhi, Ana Aparicio, Jeri Kim, Amado J Zurita-Saavedra, John C Araujo, Paul G Corn, Jessica Stover, Sue-Hwa Lin, Christopher J Logothetis, Shi-Ming Tu
BACKGROUND: We evaluated the patterns of progression and determined clinical predictors of survival in patients with castration-resistant prostate cancer (CRPCa) who received sipuleucel-T. METHODS: We retrospectively analyzed 56 consecutive patients with asymptomatic or minimally symptomatic CRPCa treated with sipuleucel-T. Age, number of bone metastases, history of prior systemic treatment, and alkaline phosphatase level (ALP) were tested as predictors of survival in a multivariate Cox proportional hazards regression model...
July 20, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28730266/-malignant-melanoma-current-status
#8
REVIEW
J K Winkler, K Buder-Bakhaya, A Dimitrakopoulou-Strauss, A Enk, J C Hassel
CLINICAL ISSUE: The incidence of malignant melanoma is continuously increasing. The prognosis of metastatic disease is still limited. STANDARD TREATMENT: Until a few years ago palliative chemotherapy with a limited response rate was the standard treatment for metastatic melanoma. TREATMENT INNOVATIONS: Immunotherapy and targeted therapy provide new treatment options. Immune checkpoint inhibitors have significantly improved the prognosis. DIAGNOSTIC WORK-UP: Regional lymph node sonography, computed tomography (CT) of the neck, chest and abdomen and brain magnetic resonance imaging (MRI) are routinely used...
July 20, 2017: Der Radiologe
https://www.readbyqxmd.com/read/28729550/anti-tumor-activity-and-immunotherapeutic-potential-of-a-bisphosphonate-prodrug
#9
Yoshimasa Tanaka, Masashi Iwasaki, Kaoru Murata-Hirai, Kenji Matsumoto, Kosuke Hayashi, Haruki Okamura, Tomoharu Sugie, Nagahiro Minato, Craig T Morita, Masakazu Toi
Bisphosphonates have benefits in breast cancer and multiple myeloma patients and have been used with adoptive immunotherapy with γδ T cells expressing Vγ2 Vδ2 TCRs. Although treatment with γδ T cells is safe, it has shown limited efficacy. Present bisphosphonates stimulate γδ T cells but were designed to inhibit bone resorption rather than treating cancer and have limited oral absorption, tumor cell entry, and cause bone side effects. The development of phosphate and phosphonate nucleotide prodrugs has led to important drugs for hepatitis C and HIV...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729154/tremelimumab-as-second-line-or-third-line-treatment-in-relapsed-malignant-mesothelioma-determine-a-multicentre-international-randomised-double-blind-placebo-controlled-phase-2b-trial
#10
Michele Maio, Arnaud Scherpereel, Luana Calabrò, Joachim Aerts, Susana Cedres Perez, Alessandra Bearz, Kristiaan Nackaerts, Dean A Fennell, Dariusz Kowalski, Anne S Tsao, Paul Taylor, Federica Grosso, Scott J Antonia, Anna K Nowak, Maria Taboada, Martina Puglisi, Paul K Stockman, Hedy L Kindler
BACKGROUND: New therapeutic strategies for malignant mesothelioma are urgently needed. In the DETERMINE study, we investigated the effects of the cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibody tremelimumab in patients with previously treated advanced malignant mesothelioma. METHODS: DETERMINE was a double-blind, placebo-controlled, phase 2b trial done at 105 study centres across 19 countries in patients with unresectable pleural or peritoneal malignant mesothelioma who had progressed after one or two previous systemic treatments for advanced disease...
July 17, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28728868/pdl1-expression-in-desmoplastic-melanoma-is-associated-with-tumor-aggressiveness-and-progression
#11
Stefan Kraft, Maria-Teresa Fernandez-Figueras, Nina A Richarz, Keith T Flaherty, Mai P Hoang
BACKGROUND: The prognostic role of programmed death ligand 1 (PDL1), CD8, and forkhead box p3 (FoxP3) expression in desmoplastic melanomas is unclear. METHODS: We correlated PDL1, p53, and Ki-67 expression with CD8(+) and FoxP3(+) immune infiltrates with clinicopathologic variables and patient outcomes in a series of 66 desmoplastic melanomas. RESULTS: Tumoral PDL1 expression (≥25%), which was seen in 21% of patients (14 of 66), significantly correlated with mixed histology, tumor thickness, mitoses, recurrence, and metastasis...
July 17, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28728794/myeloid-suppressor-cells-in-cancer-and-autoimmunity
#12
REVIEW
Antonio Sica, Marco Massarotti
A bottleneck for immunotherapy of cancer is the immunosuppressive microenvironment in which the tumor cells proliferate. Cancers harness the immune regulatory mechanism that prevents autoimmunity from evading immunosurveillance and promoting immune destruction. Regulatory T cells, myeloid suppressor cells, inhibitory cytokines and immune checkpoint receptors are the major components of the immune system acting in concert with cancer cells and causing the subversion of anti-tumor immunity. This redundant immunosuppressive network poses an impediment to efficacious immunotherapy by facilitating tumor progression...
July 17, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28728493/treating-breast-cancer-with-cell-based-approaches-an-overview
#13
Susanna Gallo, Dario Sangiolo, Fabrizio Carnevale Schianca, Massimo Aglietta, Filippo Montemurro
Breast cancer is the most common malignancy in women. Despite there being considerable progress in the treatment of this disease, metastatic dissemination is still considered an incurable condition at the present time, causing 500,000 deaths worldwide every year. Although most of the research efforts have been focused on pharmacological approaches, over the last three decades, the use of bone marrow and peripheral blood-derived cell therapy approaches have been attempted and developed. Areas covered: This review will briefly address cell therapy for breast cancer, including autologous stem cell transplantations for overcoming the myelosuppressive effects of high-dose chemotherapy, allogeneic stem cell transplants and adoptive immunotherapy using bone-marrow derived T-cells...
July 20, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28727936/helper-t-cells-and-cancer-associated-inflammation-a-new-direction-for-immunotherapy
#14
Chen Dong
CD4(+) helper T cells are critical regulators in immunity and inflammation. Growing evidence has indicated their involvement in cancer, by shaping the tumor microenvironment. In this study, I summarize latest literature on Th2 and Th17 cells in cancer-associated inflammation and propose that they may be targeted for cancer immunotherapy.
July 20, 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28726535/mismatch-repair-deficient-metastatic-colon-cancer-and-urothelial-cancer-a-case-report-of-sequential-immune-checkpoint-therapy
#15
Pooja Ghatalia, Rajeswari Nagarathinam, Harry Cooper, Daniel M Geynisman, Wafik S El-Deiry
A major recent advance in cancer therapy involves the use of immune checkpoint therapy for tumors with mismatch repair deficiency, as they have a high tumor mutation load and neoantigen burden. Approximately 4% of advanced colorectal cancer harbors a mismatch repair deficiency. When mismatch repair deficiency exists in the germline, there is increased susceptibility to a variety of cancers including colorectal cancer, uterine cancer, urothelial carcinoma, and skin cancer. Herein we report the case of a 62-year-old man with mismatch repair deficient metastatic colorectal adenocarcinoma, urothelial carcinoma and a history of sebaceous carcinomas...
July 20, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28725493/interferon-alpha-based-immunotherapies-in-the-treatment-of-b-cell-derived-hematologic-neoplasms-in-today-s-treat-to-target-era
#16
REVIEW
Li Zhang, Yu-Tzu Tai, Matthew Zhi Guang Ho, Lugui Qiu, Kenneth C Anderson
B cell lymphoma and multiple myeloma (MM) are the most common hematological malignancies which benefit from therapeutic monoclonal antibodies (mAbs)-based immunotherapies. Despite significant improvement on patient outcome following the use of novel therapies for the past decades, curative treatment is unavailable for the majority of patients. For example, the 5-year survival of MM is currently less than 50%. In the 1980s, interferon-α was used as monotherapy in newly diagnosed or previously treated MM with an overall response rate of 15-20%...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28725432/transplanters-drive-cars-to-the-clinic-by-brewing-ice-t-the-moffitt-roadmap
#17
EDITORIAL
Frederick L Locke, Claudio Anasetti
Recent single institution clinical trial successes with anti-CD19 Chimeric Antigen Receptor (CAR) T cell therapy for B cell malignancies attracted significant attention from industry. Our center sought to rapidly and safely bring industry sponsored pivotal trials to our patients and to prepare for additional cell therapy trials in solid and liquid tumors from both industry and our own investigators. We implemented a collaborative cross departmental program to provide clinical care and trial coordination for immune cell therapies...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28725431/angiosarcoma-treated-successfully-with-anti-pd-1-therapy-a-case-report
#18
Simran Sindhu, Lana H Gimber, Lee Cranmer, Ali McBride, Andrew S Kraft
BACKGROUND: Angiosarcomas are tumors of malignant endothelial origin that have a poor prognosis with a five-year survival of less than 40%. These tumors can be found in all age groups, but are more common in older patients; with the cutaneous form most common in older white men. Combined modality therapy including surgery and radiation appears to have a better outcome than each modality alone. When metastatic, agents such as liposomal doxorubicin, paclitaxel and ifosfamide have activity but it is short-lived and not curative...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28725429/pretreatment-antigen-specific-immunity-and-regulation-association-with-subsequent-immune-response-to-anti-tumor-dna-vaccination
#19
Laura E Johnson, Brian M Olson, Douglas G McNeel
BACKGROUND: Immunotherapies have demonstrated clinical benefit for many types of cancers, however many patients do not respond, and treatment-related adverse effects can be severe. Hence many efforts are underway to identify treatment predictive biomarkers. We have reported the results of two phase I trials using a DNA vaccine encoding prostatic acid phosphatase (PAP) in patients with biochemically recurrent prostate cancer. In both trials, persistent PAP-specific Th1 immunity developed in some patients, and this was associated with favorable changes in serum PSA kinetics...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28725428/highlights-of-the-31st-annual-meeting-of-the-society-for-immunotherapy-of-cancer-sitc-2016
#20
REVIEW
James L Gulley, Elizabeth A Repasky, Laura S Wood, Lisa H Butterfield
Therapeutic efforts to engage the immune system against cancer have yielded exciting breakthroughs and a growing list of approved immune-based agents across a variety of disease states. Despite the early successes and durable responses associated with treatments such as immune checkpoint inhibition, there is still progress to be made in the field of cancer immunotherapy. The 31st annual meeting of the Society for Immunotherapy of Cancer (SITC 2016), which took place November 11-13, 2016 in National Harbor, Maryland, showcased the latest advancements in basic, translational, and clinical research focused on cancer immunology and immunotherapy...
2017: Journal for Immunotherapy of Cancer
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