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PD-L1 immunohistochemistry

Nitin Chakravarti, Doina Ivan, Van A Trinh, Isabella C Glitza, Jonathan L Curry, Carlos Torres-Cabala, Michael T Tetzlaff, Roland L Bassett, Victor G Prieto, Wen-Jen Hwu
Ipilimumab, a fully human monoclonal antibody against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), is the first immune checkpoint inhibitor approved for the treatment of unresectable melanoma on the basis of its overall survival (OS) benefit. However, ipilimumab is associated with significant immune-related adverse events. We hypothesized that biomarker exploration of pretreatment tumor samples and correlation with clinical outcome would enable patient selection with an increased benefit/risk ratio for ipilimumab therapy...
October 20, 2016: Melanoma Research
Sang Byung Bae, Hyun Deuk Cho, Mee-Hye Oh, Ji-Hye Lee, Si-Hyong Jang, Soon Auck Hong, Junhun Cho, Sung Yong Kim, Sun Wook Han, Jong Eun Lee, Han Jo Kim, Hyun Ju Lee
PURPOSE: The interaction of programmed death receptor 1 (PD-1) and its ligand, programmed death receptor ligand 1 (PD-L1), negatively regulates immune responses. This study aimed to clarify PD-L1 expression levels in breast cancer through immunohistochemistry (IHC) and to evaluate associations between these findings and clinicopathologic variables, including prognosis. METHODS: PD-L1 expression was analyzed using IHC on tissue microarrays of 465 invasive breast carcinomas...
September 2016: Journal of Breast Cancer
Kentaro Inamura, Yusuke Yokouchi, Maki Kobayashi, Rie Sakakibara, Hironori Ninomiya, Sophia Subat, Hiroko Nagano, Kimie Nomura, Sakae Okumura, Tomoko Shibutani, Yuichi Ishikawa
OBJECTIVES: Compared with non-smoking counterparts, smoking-associated lung cancers have a higher mutational load, resulting in the creation of more tumor neoantigens and increased immunogenicity. B7-H3 (also known as CD276) belongs to a family of immune modulators that includes PD-1 and PD-L1 (also known as B7-H1 or CD274). Considering the evidence that PD-L1 inhibitors have been shown to be more effective against lung cancer in smokers, we herein examined the prognostic interaction of tumor B7-H3 expression level with smoking history in lung adenocarcinoma patients...
October 1, 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Congqi Dai, Ruixuan Geng, Chenchen Wang, Angela Wong, Min Qing, Jianjun Hu, Yu Sun, A W I Lo, Jin Li
Checkpoint blockade therapy has emerged as a novel approach for cancer immunotherapy in several malignancies. However, patient prognosis and disease progression relevant to immune checkpoints in gastric tumor microenvironment are not defined. This study aims to investigate the expression and prognostic significance of immune checkpoints within gastric cancer. In the study, a cohort of 398 cancer tissues from stage I to IV gastric cancer patients were assessed for programmed cell death 1 ligand 1 (PD-L1) expression and tumor-infiltrating lymphocyte (TIL) infiltration using immunohistochemistry to ascertain their survival correlation...
September 24, 2016: Molecular Oncology
Bianca Schuhmacher, Benjamin Rengstl, Claudia Döring, Julia Bein, Sebastian Newrzela, Uta Brunnberg, Hans Michael Kvasnicka, Martine Vornanen, Ralf Küppers, Martin-Leo Hansmann, Sylvia Hartmann
Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is an indolent lymphoma, but can transform into diffuse large B cell lymphoma (DLBCL), showing a more aggressive clinical behavior. Little is known about these cases on the molecular level. Therefore, the aim of the present study was to characterize DLBCL transformed from NLPHL (LP-DLBCL) by gene expression profiling (GEP). GEP revealed an inflammatory signature pinpointing to a specific host response. In a coculture model resembling this host response, DEV tumor cells showed an impaired growth behavior...
September 30, 2016: Oncotarget
Eileen E Parkes, Steven M Walker, Laura E Taggart, Nuala McCabe, Laura A Knight, Richard Wilkinson, Karen D McCloskey, Niamh E Buckley, Kienan I Savage, Manuel Salto-Tellez, Stephen McQuaid, Mary T Harte, Paul B Mullan, D Paul Harkin, Richard D Kennedy
BACKGROUND: Previously we identified a DNA damage response-deficient (DDRD) molecular subtype within breast cancer. A 44-gene assay identifying this subtype was validated as predicting benefit from DNA-damaging chemotherapy. This subtype was defined by interferon signaling. In this study, we address the mechanism of this immune response and its possible clinical significance. METHODS: We used immunohistochemistry (IHC) to characterize immune infiltration in 184 breast cancer samples, of which 65 were within the DDRD subtype...
January 2017: Journal of the National Cancer Institute
Patrick H Lizotte, Elena V Ivanova, Mark M Awad, Robert E Jones, Lauren Keogh, Hongye Liu, Ruben Dries, Christina Almonte, Grit S Herter-Sprie, Abigail Santos, Nora B Feeney, Cloud P Paweletz, Meghana M Kulkarni, Adam J Bass, Anil K Rustgi, Guo-Cheng Yuan, Donald W Kufe, Pasi A Jänne, Peter S Hammerman, Lynette M Sholl, F Stephen Hodi, William G Richards, Raphael Bueno, Jessie M English, Mark A Bittinger, Kwok-Kin Wong
BACKGROUND. Immune checkpoint blockade improves survival in a subset of patients with non-small-cell lung cancer (NSCLC), but robust biomarkers that predict response to PD-1 pathway inhibitors are lacking. Furthermore, our understanding of the diversity of the NSCLC tumor immune microenvironment remains limited. METHODS. We performed comprehensive flow cytometric immunoprofiling on both tumor and immune cells from 51 NSCLCs and integrated this analysis with clinical and histopathologic characteristics, next-generation sequencing, mRNA expression, and PD-L1 immunohistochemistry (IHC)...
September 8, 2016: JCI Insight
Franziska Erlmeier, Arndt Hartmann, Michael Autenrieth, Max Wiedemann, Philipp Ivanyi, Sandra Steffens, Wilko Weichert
Immune checkpoint inhibitors targeting the inhibitory cross talk between tumor and immune cells have been approved for therapy in renal cell carcinoma (RCC). In contrast to clear cell RCC, little is known on PD-1/PD-L1 expression patterns in rarer RCC subtypes. The aim of this study was to evaluate the prevalence, distribution and prognostic impact of PD-1 and PD-L1 expression in chromophobe (ch)RCC. Patients who underwent renal surgery due to chRCC were retrospectively evaluated. Tumor specimen was analyzed for PD-1 and PD-L1 expression by immunohistochemistry...
November 2016: Medical Oncology
Emily A Lanzel, M Paula Gomez Hernandez, Amber M Bates, Christopher N Treinen, Emily E Starman, Carol L Fischer, Deepak Parashar, Janet M Guthmiller, Georgia K Johnson, Taher Abbasi, Shireen Vali, Kim A Brogden
PURPOSE: Interaction of the programmed death-1 (PD-1) co-receptor on T cells with the programmed death-ligand 1 (PD-L1) on tumor cells can lead to immunosuppression, a key event in the pathogenesis of many tumors. Thus, determining the amount of PD-L1 in tumors by immunohistochemistry (IHC) is important as both a diagnostic aid and a clinical predictor of immunotherapy treatment success. Because IHC reactivity can vary, we developed computational simulation models to accurately predict PD-L1 expression as a complementary assay to affirm IHC reactivity...
September 29, 2016: Cancer Immunology, Immunotherapy: CII
H Kadara, M Choi, J Zhang, E P Cuentas, J R Canales, S G Gaffney, Z Zhao, C Behrens, J Fujimoto, C Chow, Y Yoo, N Kalhor, C Moran, D Rimm, S Swisher, D L Gibbons, J Heymach, E Kaftan, J P Townsend, T J Lynch, J Schlessinger, J Lee, R P Lifton, I I Wistuba, R S Herbst
BACKGROUND: Lung adenocarcinomas (LUADs) lead to the majority of deaths attributable to lung cancer. We performed whole-exome sequencing (WES) and immune profiling analyses of a unique set of clinically annotated early-stage LUADs to better understand the pathogenesis of this disease and identify clinically relevant molecular markers. METHODS: We performed WES of 108 paired stage I-III LUADs and normal lung tissues using the Illumina HiSeq 2000 platform. Ten immune markers (PD-L1, PD-1, CD3, CD4, CD8, CD45ro, CD57, CD68, FOXP3 and Granzyme B) were profiled by imaging-based immunohistochemistry in a subset of LUADs (n=92)...
September 29, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
M Choi, H Kadara, J Zhang, E P Cuentas, J R Canales, S G Gaffney, Z Zhao, C Behrens, J Fujimoto, C Chow, K Kim, N Kalhor, C Moran, D Rimm, S Swisher, D L Gibbons, J Heymach, E Kaftan, J P Townsend, T J Lynch, J Schlessinger, J Jack Lee, R P Lifton, R S Herbst, I I Wistuba
BACKGROUND: Lung squamous cell carcinoma (LUSC) accounts for 20-30% of non-small cell lung cancers (NSCLCs). There are limited treatment strategies for LUSC in part due to our inadequate understanding of the molecular underpinnings of the disease. We performed whole-exome sequencing (WES) and comprehensive immune profiling of a unique set of clinically annotated early-stage LUSCs to increase our understanding of the pathobiology of this malignancy. METHODS: Matched pairs of surgically resected stage I-III LUSCs and normal lung tissues (n=108) were analyzed by WES...
September 29, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Katharina Auer, Anna Bachmayr-Heyda, Nyamdelger Sukhbaatar, Stefanie Aust, Klaus G Schmetterer, Samuel M Meier, Christopher Gerner, Christoph Grimm, Reinhard Horvat, Dietmar Pils
The immune system plays a critical role in cancer progression and overall survival. Still, it is unclear if differences in the immune response are associated with different patterns of tumor spread apparent in high grade serous ovarian cancer patients and previously described by us. In this study we aimed to assess the role of the immune system in miliary (widespread, millet-sized lesions) and non-miliary (bigger, exophytically growing implants) tumor spread. To achieve this we comprehensively analyzed tumor tissues, blood, and ascites from 41 patients using immunofluorescence, flow cytometry, RNA sequencing, multiplexed immunoassays, and immunohistochemistry...
August 3, 2016: Oncotarget
Margaret Cocks, Diana Taheri, Mark W Ball, Stephania M Bezerra, Maria Del Carmen Rodriguez, Bernardo F P Ricardo, Trinity J Bivalacqua, Rajni B Sharma, Alan Meeker, Alcides Chaux, Arthur L Burnett, George J Netto
Penile squamous cell carcinoma (SCC) is primarily treated by surgical resection. Locally advanced and metastatic disease require a multidisciplinary treatment approach. However, mortality and morbidity remain high and novel molecular and immunotherapeutic targets are actively being sought. We investigated the expression of immune checkpoint markers in penile cancers. Fifty-three invasive penile SCCs diagnosed between 1985 and 2013 were retrieved from our surgical pathology archives. Representative formalin-fixed, paraffin-embedded archival blocks were used for the construction of 2 high-density tissue microarrays (TMAs)...
September 20, 2016: Human Pathology
Akihito Kawazoe, Takeshi Kuwata, Yasutoshi Kuboki, Kohei Shitara, Akiko Kawano Nagatsuma, Masaaki Aizawa, Takayuki Yoshino, Toshihiko Doi, Atsushi Ohtsu, Atsushi Ochiai
BACKGROUND: Antibodies against programmed death 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1) have recently demonstrated promising results in gastric cancer (GC). PD-L1 expression, the presence of tumor-infiltrating lymphocytes (TILs), and mismatch repair (MMR) deficiency have been proposed as predictive biomarkers for anti-PD-1/PD-L1 antibodies. The aim of this study was to investigate the clinical relevance of PD-L1 expression with TIL, MMR, and Epstein-Barr virus (EBV) status in GC...
September 14, 2016: Gastric Cancer
Seunggu J Han, Gerald Reis, Gary Kohanbash, Shruti Shrivastav, Stephen T Magill, Annette M Molinaro, Michael W McDermott, Philip V Theodosopoulos, Manish K Aghi, Mitchel S Berger, Nicholas A Butowski, Igor Barani, Joanna J Phillips, Arie Perry, Hideho Okada
While immunotherapy may offer promising new approaches for high grade meningiomas, little is currently known of the immune landscape in meningiomas. We sought to characterize the immune microenvironment and a potentially targetable antigen mesothelin across WHO grade I-III cases of meningiomas, and how infiltrating immune populations relate to patient outcomes. Immunohistochemistry was performed on tissue microarrays constructed from 96 meningioma cases. The cohort included 16 WHO grade I, 62 WHO grade II, and 18 WHO grade III tumors...
September 13, 2016: Journal of Neuro-oncology
Solène-Florence Kammerer-Jacquet, Laurence Crouzet, Angélique Brunot, Julien Dagher, Adélaïde Pladys, Julien Edeline, Brigitte Laguerre, Benoit Peyronnet, Romain Mathieu, Grégory Verhoest, Jean-Jacques Patard, Alexandra Lespagnol, Jean Mosser, Marc Denis, Yosra Messai, Sophie Gad-Lapiteau, Salem Chouaib, Marc-Antoine Belaud-Rotureau, Karim Bensalah, Nathalie Rioux-Leclercq
Clear cell renal cell carcinoma (ccRCC) is an aggressive tumor that is characterized in most cases by inactivation of the tumor suppressor gene VHL. The VHL/HIF/VEGF pathway thus plays a major role in angiogenesis and is currently targeted by anti-angiogenic therapy. The emergence of resistance is leading to the use of targeted immunotherapy against immune checkpoint PD1/PDL1 that restores antitumor immune response. The correlation between VHL status and PD-L1 expression has been little investigated. In this study, we retrospectively reviewed 98 consecutive cases of ccRCC and correlated PD-L1 expression by immunohistochemistry (IHC) with clinical data (up to 10-year follow-up), pathological criteria, VEGF, PAR-3, CAIX and PD-1 expressions by IHC and complete VHL status (deletion, mutation and promoter hypermethylation)...
September 13, 2016: International Journal of Cancer. Journal International du Cancer
Qian-Kun Xie, Yu-Jie Zhao, Tao Pan, Ning Lyu, Lu-Wen Mu, Shao-Long Li, Mu-De Shi, Zhen-Feng Zhang, Peng-Hui Zhou, Ming Zhao
It is well known that the aberrant expression of programmed death ligand 1 (PD-L1) on tumor cells impairs antitumor immunity. To date, in hepatocellular carcinoma (HCC), the relationship between PD-L1 expression and host-tumor immunity is not well defined. Here, the expression levels of PD-L1 and CD8(+) T cell infiltration were analyzed by immunohistochemistry (IHC) in formalin fixed paraffin embedded (FFPE) specimens from 167 HCC patients undergoing resection. A significant positive association was found between PD-L1 expression and the presence of CD8(+) T cell (p < 0...
July 2016: Oncoimmunology
Chang-Long Chen, Qiu-Zhong Pan, Jing-Jing Zhao, Ying Wang, Yong-Qiang Li, Qi-Jing Wang, Ke Pan, De-Sheng Weng, Shan-Shan Jiang, Yan Tang, Xiao-Fei Zhang, Hong-Xia Zhang, Zi-Qi Zhou, Yi-Xin Zeng, Jian-Chuan Xia
Cytokine-induced killer (CIK) cell immunotherapy represents an effective treatment strategy for treating hepatocellular carcinoma (HCC). However, the therapeutic benefits of CIK cell treatment can be influenced by differences in complex immune microenvironment between patients. Herein, we investigated the relationship between PD-L1 expression and survival benefits of CIK cell immunotherapy in HCC patients. This retrospective study included 448 HCC patients: 217 cases underwent hepatectomy alone; 231 cases received hepatectomy and post-operative CIK cell transfusion...
July 2016: Oncoimmunology
Laveniya Satgunaseelan, Ruta Gupta, Jason Madore, Noel Chia, Trina Lum, Carsten E Palme, Michael Boyer, Richard A Scolyer, Jonathan R Clark
Phase 2 clinical trials utilising novel anti-PD1/PD-L1 antibodies are being conducted in oral cavity squamous cell carcinoma (OSCC) patients. However, data regarding PD-L1 expression in OSCC is limited. The aim of this study was to characterise the PD-L1 immunohistochemical expression in OSCC and its association with clinicopathological factors. Clinicopathological review of 217 patients with OSCC was performed, including quantifying tumour-infiltrating lymphocytes. Immunohistochemistry with PD-L1, CD4 and CD8 was performed...
October 2016: Pathology
Xin Wang, Feifei Teng, Li Kong, Jinming Yu
PD-L1 is an immunoinhibitory molecule that suppresses the activation of T cells, leading to the progression of tumors. Overexpression of PD-L1 in cancers such as gastric cancer, hepatocellular carcinoma, renal cell carcinoma, esophageal cancer, pancreatic cancer, ovarian cancer, and bladder cancer is associated with poor clinical outcomes. In contrast, PD-L1 expression correlates with better clinical outcomes in breast cancer and merkel cell carcinoma. The prognostic value of PD-L1 expression in lung cancer, colorectal cancer, and melanoma is controversial...
2016: OncoTargets and Therapy
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