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pd-1 and cancer

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https://www.readbyqxmd.com/read/28230773/programmed-death-ligand-1-pd-l1-tumor-expression-is-associated-with-a-better-prognosis-and-diabetic-disease-in-triple-negative-breast-cancer-patients
#1
Gerardo Botti, Francesca Collina, Giosuè Scognamiglio, Federica Rao, Valentina Peluso, Rossella De Cecio, Michela Piezzo, Gabriella Landi, Michelino De Laurentiis, Monica Cantile, Maurizio Di Bonito
Triple Negative Breast Cancers (TNBC) subtype is an aggressive disease with poor clinical outcome. The only treatment available is surgery followed by chemotherapy or radiotherapy. Programmed death-ligand 1 (PD-L1) is a trans-membrane protein expressed on a wide variety of cells including immune cells, epithelial and vascular endothelial cells. Recently, PD-1/PD-L1 pathway signaling was described as an adaptive immune resistance mechanism enacted by the tumor cells to evade the immune response. Its presence on tumor cell membranes, acquired for this reason, through time, is an important prognostic value...
February 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28228704/pd-1-and-pd-l1-immune-checkpoint-blockade-to-treat-breast-cancer
#2
REVIEW
Andreas D Hartkopf, Florin-Andrei Taran, Markus Wallwiener, Christina B Walter, Bernhard Krämer, Eva-Maria Grischke, Sara Y Brucker
Immune checkpoint inhibition represents a major recent breakthrough in the treatment of malignant diseases including breast cancer. Blocking the programmed death receptor-1 (PD-1) and its ligand, PD-L1, has shown impressive antitumor activity and may lead to durable long-term disease control, especially in the triple-negative subtypes of breast cancer (TNBC). Although immune checkpoint blockade is generally well tolerated, specific immune-related adverse events (irAEs) may occur. This review summarizes the clinical efficacy, perspectives, and future challenges of using PD-1/PD-L1-directed antibodies in the treatment of breast cancer...
December 2016: Breast Care
https://www.readbyqxmd.com/read/28228279/loss-of-pten-is-associated-with-resistance-to-anti-pd-1-checkpoint-blockade-therapy-in-metastatic-uterine-leiomyosarcoma
#3
Suzanne George, Diana Miao, George D Demetri, Dennis Adeegbe, Scott J Rodig, Sachet Shukla, Mikel Lipschitz, Ali Amin-Mansour, Chandrajit P Raut, Scott L Carter, Peter Hammerman, Gordon J Freeman, Catherine J Wu, Patrick A Ott, Kwok-Kin Wong, Eliezer M Van Allen
Response to immune checkpoint blockade in mesenchymal tumors is poorly characterized, but immunogenomic dissection of these cancers could inform immunotherapy mediators. We identified a treatment-naive patient who has metastatic uterine leiomyosarcoma and has experienced complete tumor remission for >2 years on anti-PD-1 (pembrolizumab) monotherapy. We analyzed the primary tumor, the sole treatment-resistant metastasis, and germline tissue to explore mechanisms of immunotherapy sensitivity and resistance...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28228226/-progress-of-pd-1-pd-l1-inhibitors-in-non-small-cell-lung-cancer
#4
Zhansheng Jiang, Zhanyu Pan, Xiubao Ren
Pembrolizumab, an inhibitor target programmed death 1 (PD-1), was approved into the first line therapy in advanced non-small cell lung cancer (NSCLC). It was a milestone that immune checkpoints drugs have played an important role in the treatment system of NSCLC. The results of clinical trials revealed the superiority of PD-1/programmed death ligand 1 (PD-L1) inhibitors compared with chemotherapy in first-line, second-line and multidrug resistance phase therapy. Objective response rate (ORR) was up to 80% with pembrolizumab plus chemotherapy, and progression-free survival (PFS) with single pembrolizumab in first line was nearly 1 year (10...
February 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28224235/oral-mucosal-changes-induced-by-anticancer-targeted-therapies-and-immune-checkpoint-inhibitors
#5
REVIEW
Emmanuelle Vigarios, Joel B Epstein, Vincent Sibaud
Development of biological targeted therapies and immune checkpoint inhibitors has redefined the treatment for many cancers; however, the increasing use of new protocols has led to physicians observing a new spectrum of toxicities. To date, oral adverse events induced by these new anticancer therapies have been mainly reported using nonspecific terminology ("stomatitis," "mucosal inflammation," "mucositis") and remain poorly characterized, with the exception of mammalian target of rapamycin (mTOR) inhibitor-associated stomatitis...
February 22, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28223273/pd-l1-studies-across-tumor-types-its-differential-expression-and-predictive-value-in-patients-treated-with-immune-checkpoint-inhibitors
#6
Harriet M Kluger, Christopher R Zito, Gabriela Turcu, Marina Baine, Hongyi Zhang, Adebowale Adeniran, Mario Sznol, David L Rimm, Yuval Kluger, Lieping Chen, Justine V Cohen, Lucia B Jilaveanu
PURPOSE: With recent approval of inhibitors of PD-1 in melanoma, non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC), extensive efforts are underway to develop biomarkers predictive of response. PD-L1 expression has been most widely studied, and is more predictive in NSCLC than RCC or melanoma. We therefore studied differences in expression patterns across tumor types. EXPERIMENTAL DESIGN: We employed tissue microarrays with tumors from NSCLC, RCC or melanoma and a panel of cell lines to study differences between tumor types...
February 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28223102/inflammatory-cytokines-il-17-and-tnf-%C3%AE-up-regulate-pd-l1-expression-in-human-prostate-and-colon-cancer-cells
#7
Xun Wang, Lingyun Yang, Feng Huang, Qiuyang Zhang, Sen Liu, Lin Ma, Zongbing You
Programmed cell death protein 1 (PD-1) acts on PD-1 ligands (PD-L1 and PD-L2) to suppress activation of cytotoxic T lymphocytes. Interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) are co-expressed by T helper 17 (TH17) cells in many tumors. The purpose of this study was to test if IL-17 and TNF-α may synergistically induce PD-L1 expression in human prostate cancer LNCaP and human colon cancer HCT116 cell lines. We found that IL-17 did not induce PD-L1 mRNA expression, but up-regulated PD-L1 protein expression in HCT116 and LNCaP cells...
February 13, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28223062/nivolumab-for-previously-treated-unresectable-metastatic-anal-cancer-nci9673-a-multicentre-single-arm-phase-2-study
#8
Van K Morris, Mohamed E Salem, Halla Nimeiri, Syma Iqbal, Preet Singh, Kristen Ciombor, Blase Polite, Dustin Deming, Emily Chan, James L Wade, Lianchun Xiao, Tanios Bekaii-Saab, Luis Vence, Jorge Blando, Armeen Mahvash, Wai Chin Foo, Chimela Ohaji, Manolo Pasia, Gail Bland, Aki Ohinata, Jane Rogers, Amir Mehdizadeh, Kimberly Banks, Richard Lanman, Robert A Wolff, Howard Streicher, James Allison, Padmanee Sharma, Cathy Eng
BACKGROUND: Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy associated with infection by human papillomavirus (HPV). No consensus treatment approach exists for the treatment of metastatic disease. Because intratumoral HPV oncoproteins upregulate immune checkpoint proteins such as PD-1 to evade immune-mediated cytotoxicity, we did a trial of the anti-PD-1 antibody nivolumab for patients with metastatic SCCA. METHODS: We did this single-arm, multicentre, phase 2 trial at ten academic centres in the USA...
February 17, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28222447/impact-of-pd-l1-expression-in-patients-with-surgically-resected-non-small-cell-lung-cancer
#9
Satoshi Igawa, Yuichi Sato, Shinichiro Ryuge, Masaaki Ichinoe, Ken Katono, Yasuhiro Hiyoshi, Sakiko Otani, Ryo Nagashio, Hiroyasu Nakashima, Masato Katagiri, Jiichiro Sasaki, Yoshiki Murakumo, Yukitoshi Satoh, Noriyuki Masuda
BACKGROUND: Immunotherapy can become a crucial therapeutic option to improve the prognosis of patients with non-small-cell lung cancer (NSCLC). Here, we evaluated the impact of programmed cell death ligand-1 (PD-L1) expression in surgically resected NSCLCs. METHODS: We estimated PD-L1 expression in 229 consecutive NSCLC specimens using rabbit polyclonal antibodies to human PD-L1 in a SP263 immunohistochemical assay and evaluated PD-L1 expression for potential associations with clinicopathological parameters and survival time...
February 22, 2017: Oncology
https://www.readbyqxmd.com/read/28222333/immunoprofiling-as-a-predictor-of-patient-s-response-to-cancer-therapy-promises-and-challenges
#10
REVIEW
Daniel Bethmann, Zipei Feng, Bernard A Fox
Immune cell infiltration is common to many tumors and has been recognized by pathologists for more than 100 years. The application of digital imaging and objective assessment software allowed a concise determination of the type and quantity of immune cells and their location relative to the tumor and, in the case of colon cancer, characterized overall survival better than AJCC TNM staging. Subsequently, expression of PD-L1, by 50% or more tumor cells, identified NSCLC patients with double the response rate to anti-PD-1...
February 18, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28220772/tumour-and-host-cell-pd-l1-is-required-to-mediate-suppression-of-anti-tumour-immunity-in-mice
#11
Janet Lau, Jeanne Cheung, Armando Navarro, Steve Lianoglou, Benjamin Haley, Klara Totpal, Laura Sanders, Hartmut Koeppen, Patrick Caplazi, Jacqueline McBride, Henry Chiu, Rebecca Hong, Jane Grogan, Vincent Javinal, Robert Yauch, Bryan Irving, Marcia Belvin, Ira Mellman, Jeong M Kim, Maike Schmidt
Expression of PD-L1, the ligand for T-cell inhibitory receptor PD-1, is one key immunosuppressive mechanism by which cancer avoids eradication by the immune system. Therapeutic use of blocking antibodies to PD-L1 or its receptor PD-1 has produced unparalleled, durable clinical responses, with highest likelihood of response seen in patients whose tumour or immune cells express PD-L1 before therapy. The significance of PD-L1 expression in each cell type has emerged as a central and controversial unknown in the clinical development of immunotherapeutics...
February 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28218497/chemotherapy-induces-tumor-immune-evasion-by-upregulation-of-programmed-cell-death-ligand%C3%A2-1-expression-in-bone-marrow-stromal-cells
#12
Mengqi Yang, Panpan Liu, Kefeng Wang, Christophe Glorieux, Yumin Hu, Shijun Wen, Wenqi Jiang, Peng Huang
Programmed cell death ligand 1 (PD-L1) is a negative regulator of the immune response that enables tumor cells to escape T-cell immunity. Although PD-L1 expression in cancer cells has been extensively studied, the expression of PD-L1 in stromal cells and its clinical significance remain largely unknown. Here, we show that bone marrow stromal cells express a low level of PD-L1 and that this molecule is significantly upregulated by key drugs used in the treatment of lymphoma at clinically relevant concentrations...
December 28, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28216975/negative-oncologic-impact-of-poor-postoperative-pain-control-in-left-sided-pancreatic-cancer
#13
Eun-Ki Min, Jae Uk Chong, Ho Kyoung Hwang, Sang Joon Pae, Chang Moo Kang, Woo Jung Lee
AIM: To investigate the association between postoperative pain control and oncologic outcomes in resected pancreatic ductal adenocarcinoma (PDAC). METHODS: From January 2009 to December 2014, 221 patients were diagnosed with PDAC and underwent resection with curative intent. Retrospective review of the patients was performed based on electronic medical records system. One patient without records of numerical rating scale (NRS) pain intensity scores was excluded and eight patients who underwent total pancreatectomy were also excluded...
January 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28216880/isolation-and-characterisation-of-a-proanthocyanidin-with-antioxidative-antibacterial-and-anti-cancer-properties-from-fern-blechnum-orientale
#14
How-Yee Lai, Yau-Yan Lim, Kah-Hwi Kim
BACKGROUND: Blechnum orientale Linn. (Blechnaceae), a fern, is traditionally used in the treatment of various ailments, such as skin diseases, stomach pain, urinary bladder complaints, and also as a female contraceptive. Previously, we reported a strong radical scavenging activity, antibacterial activity and cytotoxicity against HT29 colon cancer cells by aqueous extract of B. orientale. OBJECTIVE: In this study, we attempted to isolate and identify the active compound from the aqueous extract of B...
January 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28214654/programmed-cell-death-protein-1-pd-1-inhibitor-therapy-in-patients-with-advanced-melanoma-and-preexisting-autoimmunity-or-ipilimumab-triggered-autoimmunity
#15
Ralf Gutzmer, Anika Koop, Friedegund Meier, Jessica C Hassel, Patrick Terheyden, Lisa Zimmer, Lucie Heinzerling, Selma Ugurel, Claudia Pföhler, Anja Gesierich, Elisabeth Livingstone, Imke Satzger, Katharina C Kähler
AIM: Programmed cell death protein 1 (PD-1) inhibitors are a common treatment strategy for metastatic melanoma and other tumour entities. Clinical trials usually exclude patients with preexisting autoimmune diseases, thus experience with PD-1 inhibitor (PD-1i) in this patient population is limited. PATIENTS AND METHODS: Metastatic melanoma patients with preexisting autoimmune disorders or previous ipilimumab-triggered immune-related adverse events (irAE) undergoing treatment with PD-1i from seven German skin cancer centres were evaluated retrospectively with regard to flare of the preexisting autoimmunity and development of new, not preexisting irAE as well as response to PD-1i therapy...
February 16, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28214651/a-review-on-the-evolution-of-pd-1-pd-l1-immunotherapy-for-bladder-cancer-the-future-is-now
#16
REVIEW
Joaquin Bellmunt, Thomas Powles, Nicholas J Vogelzang
The treatment of bladder cancer has evolved over time to encompass not only the traditional modalities of chemotherapy and surgery, but has been particularly impacted by the use of immunotherapy. The first immunotherapy was the live, attenuated bacterial Bacillus Calmette-Guérin vaccine, which has been the standard of care non-muscle-invasive bladder cancer since 1990. Modern immunotherapy has focused on inhibitors of checkpoint proteins, which are molecules that impede immune function, thereby allowing tumor cells to grow and proliferate unregulated...
February 2, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28214182/opportunistic-autoimmunity-secondary-to-cancer-immunotherapy-oasi-an-emerging-challenge
#17
M Kostine, L Chiche, E Lazaro, P Halfon, C Charpin, D Arniaud, F Retornaz, P Blanco, N Jourde-Chiche, C Richez, C Stavris
With "checkpoint inhibitors" targeting PD1/PD-1-ligands or CTLA-4/CD28 pathways, immunotherapy has profoundly modified therapeutic strategies in oncology. First approved in refractory metastatic neoplasms (melanoma and lung adenocarcinoma), it is now being tested broadly in other cancers and/or as adjuvant treatment. For a significant proportion of patients, immunotherapy is responsible for "immunological" events, identified as Immune-Related Adverse Events (irAEs). Owing to the increasing number of prescriptions, identification and management of specific immunological side effects is crucial and requires close collaboration between oncologists and internists and/or other organ specialists...
February 14, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/28214087/targeting-the-pd-1-pd-l1-axis-in-non-small-cell-lung-cancer
#18
REVIEW
Rajiv Kumar, Dearbhaile Collins, Saoirse Dolly, Fiona McDonald, Mary E R O'Brien, Timothy A Yap
The last decade has witnessed rapid advances in the discovery and development of immune checkpoint inhibitors in cancer medicine, particularly drugs targeting programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC). The proven antitumor efficacy coupled with low rates of drug-related toxicities observed, albeit idiosyncratic, with these novel immunotherapeutics have led to the registration of multiple PD-1 and PD-L1 inhibitors, such as nivolumab, pembrolizumab, and atezolizumab, in second-line advanced NSCLC, whereas durvalumab and avelumab are in late-phase clinical testing...
December 23, 2016: Current Problems in Cancer
https://www.readbyqxmd.com/read/28213726/pd-1-and-pd-l1-antibodies-in-cancer-current-status-and-future-directions
#19
REVIEW
Arjun Vasant Balar, Jeffrey S Weber
Immunotherapy has moved to the center stage of cancer treatment with the recent success of trials in solid tumors with PD-1/PD-L1 axis blockade. Programmed death-1 or PD-1 is a checkpoint molecule on T cells that plays a vital role in limiting adaptive immune responses and preventing autoimmune and auto-inflammatory reactivity in the normal host. In cancer patients, PD-1 expression is very high on T cells in the tumor microenvironment, and PD-L1, its primary ligand, is variably expressed on tumor cells and antigen-presenting cells within tumors, providing a potent inhibitory influence within the tumor microenvironment...
February 17, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28213003/the-expression-of-pd-l1-protein-as-a-prognostic-factor-in-lung-squamous-cell-carcinoma
#20
Kazuki Takada, Tatsuro Okamoto, Gouji Toyokawa, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Takaki Akamine, Shinkichi Takamori, Masakazu Katsura, Fumihiro Shoji, Yoshinao Oda, Yoshihiko Maehara
BACKGROUND: Programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway-targeted immunotherapy has become the standard option of care in the management of lung cancer. The expression of the PD-L1 protein in lung cancer is expected to be a prognostic factor or to predict the response to PD-1-blocking antibodies. However, the association between PD-L1 positivity and the clinicopathological features and patient outcomes in lung squamous cell carcinoma (SCC) remains unclear because the definitive cut-off value for the expression of PD-L1 protein remains to be established...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
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