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https://www.readbyqxmd.com/read/29156738/impact-of-mismatch-repair-deficiency-on-the-colorectal-cancer-immune-microenvironment
#1
Yingyi Zhang, Zhao Sun, Xinxin Mao, Huanwen Wu, Fei Luo, Xi Wu, Liangrui Zhou, Jing Qin, Lin Zhao, Chunmei Bai
Colorectal cancer patients respond inconsistently to immunotherapies, likely due to the immune microenvironments around their tumors. We analyzed the relationship between deficient mismatch repair (dMMR) and the colorectal cancer immune microenvironment to identify predictors of effective immunotherapy. Colorectal cancer patients (n=113) who had undergone surgical resection were divided into dMMR and proficient mismatch repair (pMMR) groups. The levels of immune checkpoint proteins, including programmed cell death 1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), indoleamine 2,3 dioxygenase and CD8 were assessed immunohistochemically...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156488/association-of-pd-l1-expression-with-treatment-outcomes-in-patients-with-braf-mutation-positive-melanoma-treated-with-vemurafenib-or-cobimetinib-combined-with-vemurafenib
#2
Matthew J Wongchenko, Antoni Ribas, Brigitte Dréno, Paolo A Ascierto, Grant A McArthur, Jorge D Gallo, Isabelle A Rooney, Jessie Hsu, Hartmut Koeppen, Yibing Yan, James Larkin
The prognostic significance of programmed death ligand-1 (PD-L1) on treatment outcomes in patients receiving BRAF with or without MEK inhibitors is not well understood. This retrospective exploratory analysis evaluated the association of tumour PD-L1 expression with progression-free survival (PFS) and overall survival (OS) among 210 patients in the coBRIM trial treated with cobimetinib plus vemurafenib or placebo plus vemurafenib. In the vemurafenib cohort, there was a trend of increased PFS and OS in those with PD-L1(+) melanoma, with hazard ratios (HRs) (PD-L1(+) versus PD-L1(-) ) of 0...
November 20, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29156447/pd-1-blockade-in-advanced-nsclc-a-focus-on-pembrolizumab
#3
REVIEW
Solange Peters, Keith M Kerr, Rolf Stahel
Non-small cell lung cancer (NSCLC) is one of the most prevalent cancers and is responsible for a large proportion of all cancer-related deaths. Current treatment options are inadequate, reflecting a substantial unmet clinical need. Increasing knowledge regarding the mechanisms and genetic aberrations underlying tumor development and growth has heralded a new era of therapy in oncology, moving away from indiscriminate cytotoxic chemotherapy toward more finely focused, targeted medicine. The development of small-molecule drugs and monoclonal antibodies directed toward specific components of dysfunctional molecular or immune pathways, and mutated genes specific to particular cancer types, is leading the field to more personalized and less toxic treatment options, many of which have demonstrated greater efficacy and survival benefits than their chemotherapeutic counterparts...
October 23, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29155997/immune-activation-and-benefit-from-avelumab-in-ebv-positive-gastric-cancer
#4
Anshuman Panda, Janice M Mehnert, Kim M Hirshfield, Greg Riedlinger, Sherri Damare, Tracie Saunders, Michael Kane, Levi Sokol, Mark N Stein, Elizabeth Poplin, Lorna Rodriguez-Rodriguez, Ann W Silk, Joseph Aisner, Nancy Chan, Jyoti Malhotra, Melissa Frankel, Howard L Kaufman, Siraj Ali, Jeffrey S Ross, Eileen P White, Gyan Bhanot, Shridar Ganesan
Response to immune checkpoint therapy can be associated with a high mutation burden, but other mechanisms are also likely to be important. We identified a patient with metastatic gastric cancer with meaningful clinical benefit from treatment with the anti-programmed death-ligand 1 (PD-L1) antibody avelumab. This tumor showed no evidence of high mutation burden or mismatch repair defect but was strongly positive for presence of Epstein-Barr virus (EBV) encoded RNA. Analysis of The Cancer Genome Atlas gastric cancer data (25 EBV+, 80 microsatellite-instable [MSI], 310 microsatellite-stable [MSS]) showed that EBV-positive tumors were MSS...
November 15, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29155514/the-prognostic-effect-of-neoadjuvant-chemoradiotherapy-on-the-change-of-pd-l1-expression-in-patients-with-locally-advanced-rectal-adenocarcinoma
#5
Igor Richter, Tomas Jirasek, Josef Dvorak, Eva Cermakova, Petra Rehakova, Jiri Bartos
PURPOSE: To evaluate the prognostic effect of neoadjuvant chemoradiotherapy on the change of programmed death ligand 1 (PD-L1) expression in patients with locally advanced rectal adenocarcinoma, by comparing PD-L1 expression in pretreatment biopsies and PD-L1 expression in pathological specimens after neoadjuvant chemoradiotherapy. METHODS: A total of 25 patients with rectal adenocarcinoma were evaluated. Patients were treated by neoadjuvant chemoradiotherapy (radiotherapy:44Gy normofraxionation; chemotherapy: capecitabine 825 mg/m(2) in two daily doses)...
July 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29155348/progress-and-challenges-of-predictive-biomarkers-of-anti-pd-1-pd-l1-immunotherapy-a-systematic-review
#6
Feifei Teng, Xiangjiao Meng, Li Kong, Jinming Yu
Despite the marked success of applications of PD-1/PD-L1 checkpoint blockades in clinical, the efficacy and responsiveness of these agents varies greatly among different tumor types and across individual patients. Therefore, establishment of predictive biomarkers for checkpoint blockades is of the most importance to maximize the therapeutic benefits. In this review, we discuss the current progress and challenges of developing predictive biomarkers of immunotherapy responsiveness, aiming to provide some directions for future studies...
November 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29155219/complement-anaphylatoxins-c3a-and-c5a-emerging-roles-in-cancer-progression-and-treatment
#7
REVIEW
Daniel Ajona, Sergio Ortiz-Espinosa, Ruben Pio
Recent insights into the role of complement anaphylatoxins C3a and C5a in cancer provide new opportunities for the development of innovative biomarkers and therapeutic strategies. These two complement activation products can maintain chronic inflammation, promote an immunosuppressive microenvironment, induce angiogenesis, and increase the motility and metastatic potential of cancer cells. Still, the diverse heterogeneity of responses mediated by these peptides poses a challenge both to our understanding of the role played by these molecules in cancer progression and to the development of effective treatments...
November 16, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29153898/the-significance-of-the-pd-l1-expression-in-non-small-cell-lung-cancer-trenchant-double-swords-as-predictive-and-prognostic-markers
#8
REVIEW
Kazuki Takada, Gouji Toyokawa, Fumihiro Shoji, Tatsuro Okamoto, Yoshihiko Maehara
Lung cancer is the leading cause of death due to cancer worldwide. Surgery, chemotherapy, and radiotherapy have been the standard treatment for lung cancer, and targeted molecular therapy has greatly improved the clinical course of patients with non-small-cell lung cancer (NSCLC) harboring driver mutations, such as in epidermal growth factor receptor and anaplastic lymphoma kinase genes. Despite advances in such therapies, the prognosis of patients with NSCLC without driver oncogene mutations remains poor. Immunotherapy targeting programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) has recently been shown to improve the survival in advanced NSCLC...
October 28, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/29152083/programmed-cell-death-1-expression-is-associated-with-inferior-survival-in-patients-with-primary-central-nervous-system-lymphoma
#9
Hyunsoo Cho, Se Hoon Kim, Soo-Jeong Kim, Jong Hee Chang, Woo-Ick Yang, Chang-Ok Suh, Yu Ri Kim, Ji Eun Jang, June-Won Cheong, Yoo Hong Min, Jin Seok Kim
Programmed cell death 1 (PD-1) and its ligands PD-L1/PD-L2 have been shown to mediate immune evasion in various cancers, but their prognostic implications in patients with primary central nervous system lymphoma (PCNSL) are poorly understood. Therefore, we analyzed 76 PCNSL patients at initial diagnosis who were treated homogenously with high-dose methotrexate-based chemotherapy, and evaluated the prognostic roles of high immunohistochemical PD-1, PD-L1, and PD-L2 expression. The cut-off values for high PD-1 (≥ 70 cells/high power field [HPF]), PD-L1 (≥ 100 cells/HPF), and PD-L2 (≥ 100 cells/HPF) were determined by the area under the receiver operating characteristic curve...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152077/concordance-of-programmed-death-ligand-1-expression-between-primary-and-metastatic-non-small-cell-lung-cancer-by-immunohistochemistry-and-rna-in-situ-hybridization
#10
Hye Ryun Kim, Yoon Jin Cha, Min Hee Hong, Manoj Gandhi, Shauna Levinson, Inkyung Jung, Jin Gu Lee, Chang Young Lee, Byoung Chul Cho, Sang-Jun Ha, Hyo Sup Shim
We investigated the concordance of programmed death-ligand 1 (PD-L1) expression between primary cancer at initial diagnosis and metastasis at recurrence in resected non-small cell lung cancer (NSCLC). PD-L1 expression was evaluated using the SP142 assay in 37 NSCLC patients with paired primary lung cancer and surgically resected metastases at recurrence. PD-L1 positivity was defined as immunohistochemistry (IHC) and also evaluated by RNA in situ hybridization (RISH). The concordance rate of PD-L1 between primaries and metastases and correlation with clinicopathological factors were analyzed...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29150906/pretreatment-advanced-lung-cancer-inflammation-index-ali-for-predicting-early-progression-in-nivolumab-treated-patients-with-advanced-non-small-cell-lung-cancer
#11
Takayuki Shiroyama, Hidekazu Suzuki, Motohiro Tamiya, Akihiro Tamiya, Ayako Tanaka, Norio Okamoto, Kenji Nakahama, Yoshihiko Taniguchi, Shun-Ichi Isa, Takako Inoue, Fumio Imamura, Shinji Atagi, Tomonori Hirashima
Programmed death-ligand 1 (PD-L1) expression status is inadequate for indicating nivolumab in patients with non-small cell lung cancer (NSCLC). Because the baseline advanced lung cancer inflammation index (ALI) is reportedly associated with patient outcomes, we investigated whether the pretreatment ALI is prognostic in NSCLC patients treated with nivolumab. We retrospectively reviewed the medical records of all patients treated with nivolumab for advanced NSCLC between December 2015 and May 2016 at three Japanese institutes...
November 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29147863/prognostic-relevance-of-programmed-cell-death-ligand-1-expression-in-glioblastoma
#12
Kyu Sang Lee, Kyoungyul Lee, Sumi Yun, Seyoung Moon, Yujun Park, Jung Ho Han, Chae-Yong Kim, Hye Seung Lee, Gheeyoung Choe
The aim of this study was to determine the clinicopathological significance of programmed cell death ligand 1 (PD-L1) expression in glioblastoma (GBM). In a retrospective cohort of 115 consecutive patients with GBM, PD-L1 expression was determined using immunohistochemistry (IHC). Membranous and fibrillary PD-L1 staining of any intensity in > 5% neoplastic cells and tumour infiltrating immune cells (TIIs) was considered positive staining. In addition, isocitrate dehydrogenase-1 (IDH-1) (R132H) expression and cluster of differentiation 3 (CD3)-positive T-cell infiltration were investigated using IHC...
November 16, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29147618/programmed-cell-death-ligands-expression-in-phaeochromocytomas-and-paragangliomas-relationship-with-the-hypoxic-response-immune-evasion-and-malignant-behavior
#13
David J Pinato, James R Black, Sebastian Trousil, Roberto E Dina, Pritesh Trivedi, Francesco A Mauri, Rohini Sharma
The hypoxic response underlies the pathogenesis and malignant behavior of PCC/PGL. Regulation of PD-1 receptor-ligand signaling, a therapeutically actionable driver of the anti-tumor immune response, is a hypoxic-driven trait across malignancies. We evaluated the prognostic role of PD ligands in association with biomarkers of hypoxia and angiogenesis in patients with PCC/PGL. Tissue microarrays sections including consecutive cases diagnosed between 1983-2011 were stained for PD-L1 and 2, hypoxia inducible factor 1a (Hif-1a), Carbonic Anhydrase IX (CaIX), Vascular Endothelial Growth Factor-A (VEGF-A)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147610/host-immune-response-index-in-gastric-cancer-identified-by-comprehensive-analyses-of-tumor-immunity
#14
Charny Park, Junhun Cho, Jeeyun Lee, So Young Kang, Ji Yeong An, Min Gew Choi, Jun Ho Lee, Tae Sung Sohn, Jae Moon Bae, Sung Kim, Seung Tae Kim, Se Hoon Park, Joon Oh Park, Won Ki Kang, Insuk Sohn, Sin Ho Jung, Myung-Soo Kang, Kyoung-Mee Kim
Tumor infiltrating lymphocytes (TIL) in Epstein-Barr virus (EBV)-associated/microsatellite-unstable (MSI) gastric carcinomas (GC) constitute immune-active principal cellular components of tumor microenvironment and contribute to better prognosis. With the remarkable success of cancer immunotherapies, there is an urgent need for a comprehensive understanding of tumor-immune interactions in patients with GC in the context of host immune response. To identify GC subtype-specific immune response gene set, we tested differentially expressed genes for MSI and EBV+ GC subtypes in randomly selected test set (n = 278) in merged ACRG-SMC microarray and TCGA RNA sequencing data set...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147606/temporal-and-spatial-heterogeneity-of-programmed-cell-death-1-ligand-1-expression-in-malignant-mesothelioma
#15
Simone B S P Terra, Aaron S Mansfield, Haidong Dong, Tobias Peikert, Anja C Roden
Background: Programmed Cell Death 1-Ligand 1 (PD-L1) and Programmed Death Protein 1 (PD-1) blocking antibodies are promising immunotherapies for malignancies. We have previously shown PD-L1 expression in 40% of malignant mesothelioma (MM); however, the temporal and spatial heterogeneity of its expression has not been thoroughly studied. We compared PD-L1 expression between paired primary and metastatic MM. Design: Pathology files (1995-2016) were searched for MM with tissue from multiple sites and/or time points...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147605/egfr-mutation-correlates-with-uninflamed-phenotype-and-weak-immunogenicity-causing-impaired-response-to-pd-1-blockade-in-non-small-cell-lung-cancer
#16
Zhong-Yi Dong, Jia-Tao Zhang, Si-Yang Liu, Jian Su, Chao Zhang, Zhi Xie, Qing Zhou, Hai-Yan Tu, Chong-Rui Xu, Li-Xu Yan, Yu-Fa Li, Wen-Zhao Zhong, Yi-Long Wu
Patients with EGFR mutations showed unfavorable response to programmed cell death-1 (PD-1) blockade immunotherapy in non-small cell lung cancer (NSCLC). Yet the underlying association between EGFR mutation and immune resistance remains largely unclear. We performed an integrated analysis of PD-ligand 1(PD-L1)/CD8 expression and mutation profile based on the repository database and resected early-stage NSCLC in Guangdong Lung Cancer Institute (GLCI). Meanwhile, 2 pool-analyses were set to clarify the correlation between EGFR mutation and PD-L1 expression, and the association of EGFR status with response to anti-PD-1/L1 therapy...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147602/gdnf-secreted-by-nerves-enhances-pd-l1-expression-via-jak2-stat1-signaling-activation-in-hnscc
#17
Chengzhong Lin, Wei Cao, Zhenhu Ren, Yu Tang, Chunye Zhang, Rong Yang, Yiming Chen, Zheqi Liu, Canbang Peng, Lizhen Wang, Xu Wang, Tong Ji
Programmed death ligand 1 (PD-L1) functions as a key immune inhibitory factor by binding with its receptor, programmed death 1 (PD-1), to induce immune cell dysfunction and escape of the immune system. However, the mechanisms of PD-L1 expression under growth factor stimulation are not well characterized. Here, we demonstrate a novel role for glial cell line-derived neurotrophic factor (GDNF) in upregulating PD-L1 expression in head and neck squamous cell carcinoma (HNSCC). The expression and correlation of PD-L1, GDNF and perineural invasion (PNI) status were evaluated by bioinformatics analysis of TCGA database and IHC assays from 145 HNSCC patients...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29146737/rheumatic-disorders-associated-with-immune-checkpoint-inhibitors-in-patients-with-cancer-clinical-aspects-and-relationship-with-tumour-response-a-single-centre-prospective-cohort-study
#18
Marie Kostine, Léa Rouxel, Thomas Barnetche, Rémi Veillon, Florent Martin, Caroline Dutriaux, Léa Dousset, Anne Pham-Ledard, Sorilla Prey, Marie Beylot-Barry, Amaury Daste, Marine Gross-Goupil, Julie Lallier, Alain Ravaud, Edouard Forcade, Bernard Bannwarth, Marie-Elise Truchetet, Christophe Richez, Nadia Mehsen, Thierry Schaeverbeke
OBJECTIVES: To evaluate the prevalence and type of rheumatic immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors (ICIs), as well as the correlation with tumour response. METHODS: This was a single-centre prospective observational study including all cancer patients receiving ICIs. The occurrence of irAEs and tumour response was assessed on a regular basis. Patients who experienced musculoskeletal symptoms were referred to the department of rheumatology for clinical evaluation and management...
November 16, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29146060/clinicopathologic-correlation-of-programmed-death-ligand-1-expression-in-non-small-cell-lung-carcinomas-a-report-from-india
#19
Archana George Vallonthaiel, Prabhat Singh Malik, Varsha Singh, Vinay Kumar, Sunil Kumar, Mehar Chand Sharma, Sandeep Mathur, Sudheer Arava, Randeep Guleria, Deepali Jain
INTRODUCTION: Increased expression of Programmed death ligand-1 (PD-L1) on cancer cells and immune cells predict response to PD-1/PDL1 inhibitors. Data regarding frequency and pattern of PD-L1 expression in NSCLC from India is not available. OBJECTIVES: To analyse PD-L1 expression on tumour cells (TC) and immune cells (IC) and to correlate PD-L1 expression with baseline clinico-pathological characteristics, oncogenic drivers and outcome data. MATERIALS AND METHODS: PD-L1 expression on tumour cells and immune cells was analysed...
December 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/29145737/pembrolizumab-as-first-line-therapy-for-metastatic-non-small-cell-lung-cancer
#20
Martin Reck
This review describes trials evaluating the monoclonal antibody pembrolizumab (an immunotherapy that blocks the interaction between programmed death-1 and programmed death-ligand 1 and 2 [PD-L1/PD-L2]) as first-line therapy for advanced non-small-cell lung cancer (NSCLC). In the Phase III KEYNOTE-024 study, pembrolizumab monotherapy significantly improved progression-free survival (primary end point) and overall survival, and was associated with fewer adverse events compared with platinum-based chemotherapy in patients with NSCLC with PD-L1 expression on ≥50% of tumor cells...
November 17, 2017: Immunotherapy
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