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https://www.readbyqxmd.com/read/28740692/durable-complete-response-to-nivolumab-in-a-patient-with-hiv-and-metastatic-non-small-cell-lung-cancer
#1
Brennan McCullar, Taylor Alloway, Michael Martin
Programmed death 1 (PD-1) inhibitors have been shown to increase overall survival in non-small cell lung cancer (NSCLC) patients. HIV patients have increased expression of PD-1 on their T-cell surfaces. We describe a patient with well-controlled HIV and NSCLC who underwent treatment with nivolumab and had a durable complete response (CR) with his viral load remaining undetectable. To date there is only one case report of a cancer patient with melanoma and with HIV treated with a programmed death ligand 1 (PD-L1) inhibitor...
June 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28739710/discrepancy-in-programmed-cell-death-ligand-1-between-primary-and-metastatic-non-small-cell-lung-cancer
#2
Shinkichi Takamori, Gouji Toyokawa, Isamu Okamoto, Kazuki Takada, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Takaki Akamine, Masakazu Katsura, Nobutaka Mukae, Fumihiro Shoji, Tatsuro Okamoto, Yoshinao Oda, Toru Iwaki, Koji Iihara, Yoichi Nakanishi, Yoshihiko Maehara
AIM: To investigate the discordance in the programmed cell death-ligand 1 (PD-L1) expression between primary and metastatic tumors and analyze the association between the discordance and the clinical factors in non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Twenty-one NSCLC patients who underwent surgery or biopsy for paired primary and metastatic lesions at our Institution from 2005 to 2016 were analyzed. Lesions with the PD-L1 expression being ≥5% were considered PD-L1-positive...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28739315/combination-therapy-of-radiotherapy-and-anti-pd-1-pd-l1-treatment-in-non-small-cell-lung-cancer-a-mini-review
#3
REVIEW
Shinkichi Takamori, Gouji Toyokawa, Kazuki Takada, Fumihiro Shoji, Tatsuro Okamoto, Yoshihiko Maehara
Immune checkpoint inhibitors against programmed cell death-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) are a standard pharmacologic therapy for patients with non-small-cell lung cancer (NSCLC). Substantial data have accumulated in recent years showing that radiotherapy combined with immunotherapy is more effective than monotherapy alone. Preclinical studies have shown that PD-L1 expression is upregulated on tumor cells after radiotherapy, resulting in the synergistically enhanced antitumor effect of irradiation and PD-L1 blockade...
July 6, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28732383/radiation-alters-pd-l1-nkg2d-ligand-levels-in-lung-cancer-cells-and-leads-to-immune-escape-from-nk-cell-cytotoxicity-via-il-6-mek-erk-signaling-pathway
#4
Ming Jing Shen, Li Jun Xu, Li Yang, Ying Tsai, Peter C Keng, Yongbing Chen, Soo Ok Lee, Yuhchyau Chen
We investigated whether radiation influences the susceptibility of non-small cell lung cancer (NSCLC) cells to NK cell mediated cytotoxicity. We found radiation treatment increased expression of programmed cell death ligand 1 (PD-L1), but decreased NK group 2, member D (NKG2D) ligand expressions in A549 and H157 NSCLC cells. Both types of changes would have protected tumor cells from the cytotoxic action of NK cells. Consistently, we detected similar alteration in these molecules in radioresistant A549R26-1 and H157R24-1 subline cells...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28730140/current-advances-in-checkpoint-inhibitors-lessons-from-non-central-nervous-system-cancers-and-potential-for-glioblastoma
#5
REVIEW
Natasha Lakin, Robert Rulach, Stefan Nowicki, Kathreena M Kurian
The adaptive immune system depends on the sequence of antigen presentation, activation, and then inhibition to mount a proportionate response to a threat. Tumors evade the immune response partly by suppressing T-cell activity using immune checkpoints. The use of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1) antibodies counteract this suppression, thereby enhancing the antitumor activity of the immune system. This approach has proven efficacy in melanoma, renal cancer, and lung cancer...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28727766/clinical-implications-of-the-novel-cytokine-il-38-expressed-in-lung-adenocarcinoma-possible-association-with-pd-l1-expression
#6
Kazuki Takada, Tatsuro Okamoto, Masaki Tominaga, Koji Teraishi, Takaki Akamine, Shinkichi Takamori, Masakazu Katsura, Gouji Toyokawa, Fumihiro Shoji, Masaki Okamoto, Yoshinao Oda, Tomoaki Hoshino, Yoshihiko Maehara
Interleukin (IL)-38, a novel member of the IL-1 cytokine family, is homologous to IL-1 receptor antagonist (IL-1Ra) and IL-36Ra, and has been reported to act as an antagonist. IL-38 expression is found in tonsil, placenta, and spleen, and recent studies suggest an association between IL-38 and autoimmune diseases. However, whether IL-38 plays a role in carcinogenesis or cancer growth is unclear. In the present study, we identified increases in IL-38 expression by immunohistochemistry in multiple types of cancer cells...
2017: PloS One
https://www.readbyqxmd.com/read/28725431/angiosarcoma-treated-successfully-with-anti-pd-1-therapy-a-case-report
#7
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/28719380/comparison-of-different-antibody-clones-for-immunohistochemistry-detection-of-programmed-cell-death-ligand-1-pd-l1-on-non-small-cell-lung-carcinoma
#8
Edwin R Parra, Pamela Villalobos, Barbara Mino, Jaime Rodriguez-Canales
Programmed cell death ligand 1 (PD-L1) is a major immune checkpoint protein that mediates antitumor immune suppression and response. Preliminary data suggest that its detection using immunohistochemistry (IHC) in formalin-fixed and paraffin-embedded tissues may predict clinical response to PD-1/PD-L1 therapy. In diagnostic pathology, it is essential to count with a validated IHC that can reliably detect PD-L1-positive cases. The present study was conducted to compare and validate different PD-L1 commercial clones and identify which ones can be reliably used by surgical pathologist to detect PD-L1 expression in human cancer tissues...
July 17, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28716463/combination-strategies-on-the-basis-of-immune-checkpoint-inhibitors-in-non-small-cell-lung-cancer-where-do-we-stand
#9
REVIEW
Meng Qiao, Tao Jiang, Shengxiang Ren, Caicun Zhou
The era of immune checkpoint inhibitors, especially programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) antibodies in the treatment of advanced non-small-cell lung cancer (NSCLC) is coming. Because of the lack of the definite biomarkers to select the optimal responders, only approximately 20% of patients with advanced NSCLC would respond to single checkpoint inhibitors-based immunotherapy. Moreover, primary or acquired resistance to conventional therapies is inevitable in most cases. Thus, combinations are pushed to move forward to be an alternative strategy and surely, it would be a future direction...
June 23, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28716069/angiosarcoma-treated-successfully-with-anti-pd-1-therapy-a-case-report
#10
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...
July 18, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28714960/bin1-reverses-pd-l1-mediated-immune-escape-by-inactivating-the-c-myc-and-egfr-mapk-signaling-pathways-in-non-small-cell-lung-cancer
#11
J Wang, Y Jia, S Zhao, X Zhang, X Wang, X Han, Y Wang, M Ma, J Shi, L Liu
Non-small cell lung cancer (NSCLC) is one of the most common and malignant carcinoma worldwide, and the incidence and mortality are increasing rapidly. Immunotherapy targeting programmed death 1/programmed death ligand 1 (PD-L1) signaling has shown prominent clinical effects in treating NSCLC; however, a poor understanding of the associated regulating molecular mechanisms of PD-L1 has become one of the biggest obstacles for further improving efficacy. Bridging integrator-1 (BIN1) can regulate numerous cancer-related molecules to exert multiple tumor-suppressing effects by either interacting or not interacting with c-MYC...
July 17, 2017: Oncogene
https://www.readbyqxmd.com/read/28714780/atezolizumab-for-the-treatment-of-non-small-cell-lung-cancer
#12
Fernando C Santini, Charles M Rudin
The immune system can restrain or promote cancer development and growth. Antibodies targeting immune checkpoints have revolutionized cancer treatment. Among the best responses have been in non-small cell lung cancer (NSCLC) which is largely caused by chronic exposure to carcinogens; associated with high neoantigen creation and sensitization to immune recognition. Atezolizumab was the first approved antibody that targets the PD-1 ligand (PD-L1). Areas Covered: This drug profile article covers the basics of the cancer-immunity cycle and reviews some aspects of innate and adaptive immunology...
July 17, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28713682/predictive-biomarkers-of-immunotherapy-for-non-small-cell-lung-cancer-results-from-an-experts-panel-meeting-of-the-italian-association-of-thoracic-oncology
#13
REVIEW
Cesare Gridelli, Andrea Ardizzoni, Massimo Barberis, Federico Cappuzzo, Francesca Casaluce, Romano Danesi, Giancarlo Troncone, Filippo De Marinis
Unleashing the potential of immune system to fight cancer has become one of the main promising treatment modalities for advanced non-small cell lung cancer (NSCLC). The knowledge of numerous factors that come into play in the cancer-immunity cycle provide a wide range of potential therapeutic targets, including monoclonal antibodies that inhibits the programmed death-1 (PD-1) checkpoint pathway. Over the last two years, nivolumab, pembrolizumab and atezolizumab received approval for treatment of pretreated advanced NSCLC, and more recently, immunotherapy with pembrolizumab is the new standard of care as first-line in patients with high levels of programmed death-ligand 1 (PD-L1) expression...
June 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28711968/local-and-systemic-immunity-predict-survival-in-patients-with-pulmonary-sarcomatoid-carcinoma
#14
Erin Schenk, Jennifer Boland, Aaron Mansfield, Marie Christine Aubry, Allan Dietz
Pulmonary sarcomatoid cancer (PSC) is a rare, aggressive subtype of non-small cell lung cancer, and measures of local and systemic immunity as biomarkers are incompletely known. We performed this study to characterize the leukocyte composition within the tumor, stroma, and peripheral blood in patients with PSC and correlated our findings with overall survival. Tissue from 30 patients diagnosed with PSC was evaluated by IHC for the presence of CD3(+), CD14(+), and CD19(+) cells and PD-L1 expression. A lymphocyte-to-monocyte ratio (LMR) was calculated for the tumor microenvironment (TME) and peripheral blood...
August 2017: Medical Oncology
https://www.readbyqxmd.com/read/28709816/-current-knowledge-on-perioperative-treatments-of-non-small-cell-lung-carcinomas
#15
REVIEW
S Brosseau, C Naltet, M Nguenang, V Gounant, P Mordant, B Milleron, Y Castier, G Zalcman
Surgery is still the main treatment in early-stage of non-small cell lung cancer with 5-year survival of stage IA patients exceeding 80%, but 5-year survival of stage II patients rapidly decreasing with tumor size, N status, and visceral pleura invasion. The major metastatic risk in such patients has supported clinical research assessing systemic or loco-regional perioperative treatments. Modern phase 3 trials clearly validated adjuvant or neo-adjuvant platinum-based chemotherapy in resected stage I-III patients as a standard treatment of which value has been reassessed several independent meta-analyses, showing a 5% benefit in 5y-survival, and a decrease of the relative risk for death around from 12 to 25%...
July 11, 2017: Revue des Maladies Respiratoires
https://www.readbyqxmd.com/read/28705024/medi-4736-durvalumab-in-non-small-cell-lung-cancer
#16
Arnaud Jeanson, Fabrice Barlesi
Immune checkpoint inhibitors (ICI) are now a therapeutic option for advanced non-small cell lung cancer (NSCLC) patients. ICI, such as the PD-1 inhibitors nivolumab and pembrolizumab and the PD-L1 inhibitor atezolizumab, have already been marketed for the treatment of pretreated patients with advanced NSCLC. Other notable PD-L1 inhibitors under development include avelumab and durvalumab. Areas covered: This article reviews literature on durvalumab development, from the preclinical data to the results of phase III clinical trials, whether published or presented at international scientific conferences...
July 13, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28700789/hair-repigmentation-during-immunotherapy-treatment-with-an-anti-programmed-cell-death-1-and-anti-programmed-cell-death-ligand-1-agent-for-lung-cancer
#17
Noelia Rivera, Aram Boada, M Isabel Bielsa, M Teresa Fernández-Figueras, Enric Carcereny, M Teresa Moran, Carlos Ferrándiz
Importance: New targeted therapies for cancer have been released in recent years, opening new horizons in the treatment of patients with cancer. However, their related adverse events (AE) are not fully characterized. Hair repigmentation (HR) is a nondescribed effect secondary to anti-programmed cell death 1 (anti-PD-1) and anti-programmed cell death ligand 1 (anti-PD-L1 ) therapy for treatment of lung cancer (LC), in opposition to the vitiligo reactions that develop during melanoma treatment...
July 12, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28697066/viral-induced-modulation-of-multiple-checkpoint-proteins-in-cancers
#18
Gerard J Nuovo, Virginia A Folcik, Cynthia Magro
Therapy with checkpoint inhibitors represents a major advance in cancer treatment. The purpose of this study was to examine the expression patterns of the checkpoint proteins programmed death ligand 1 (PD L1), PD L2, indoleamine 2,3-dioxygenase 1 (IDO1), and cytotoxic T-lymphocyte antigen 4 (CTLA4) in cancers including those associated with viral infections. Normal, noninflamed tissues rarely express checkpoint proteins with exceptions including the placenta and stomach. Expression of PD L1 was noted in 30%, PD L2 in 18%, IDO1 in 13%, and CTLA4 in 14% of 333 nonviral malignancies including endometrial, ovarian, lung, and breast cancers...
July 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28697065/accurate-pd-l1-protocols-for-non-small-cell-lung-cancer-can-be-developed-for-automated-staining-platforms-with-clone-22c3
#19
Rasmus Røge, Mogens Vyberg, Søren Nielsen
Treatment using immunotherapy against PD-L1 or PD-1 has become one of the hottest topics in Pathology and Oncology. Correct selection of patients eligible for treatment requires optimal immunohistochemical staining protocols. Treatment with pembrolizumab requires diagnostic examination of the patient's tumour using the companion diagnostic Ready-To-Use pharmDx kit from Dako Agilent based on the mAb 22C3 clone on the Autostainer platform. However, not all diagnostic pathology labs have access to this staining platform...
July 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28694003/pd-l1-and-immune-escape-insights-from-melanoma-and-other-lineage-unrelated-malignancies
#20
Noah Frydenlund, Meera Mahalingam
One of the major breakthroughs in oncology in the past decade has been the research and development of immune checkpoint inhibitors. Since the discovery of the PD-1/PD-L1 axis as a key mediator in peripheral self-tolerance and the subsequent discovery of its role promoting immune escape in cancers, the PD-1/PD-L1 pathway has produced considerable excitement from both a scientific and therapeutic stand point. The past decade has seen an explosion in the number of clinical trials utilizing antI-PD-1/PD-L1 therapy...
July 7, 2017: Human Pathology
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