Citations to this article
Glenn J. Hanna, … , Laura E. MacConaill, Robert I. Haddad
Published February 22, 2018
Citation Information: JCI Insight. 2018;3(4):e98811. https://doi.org/10.1172/jci.insight.98811.
Citation Information: JCI Insight. 2018;3(4):e98811. https://doi.org/10.1172/jci.insight.98811.
Abstract
Programmed cell death protein 1 (PD-1) inhibitors have efficacy in treating squamous cell carcinoma of the head and neck (SCCHN), but objective response rates are low. PD-1 ligand (PD-L1) expression alone is not considered a robust predictor of response and additional biomarkers are needed. This 3-year observational cohort followed 126 SCCHN patients treated with anti–PD-1/L1 therapy. Prior to treatment, 81 (64%) had targeted massively parallel tumor sequencing. Of these, 42 (52%) underwent fluorescence-activated cell sorting and PD-L1 immunohistochemistry for tumor immunoprofiling. Six (5%) complete responses (CRs) and 11 (9%) partial responses (PRs) were observed. Those treated with prior chemotherapy (98, 78%) versus only surgery and/or radiation had longer overall survival (OS) (10 vs. 3 months, P = 0.02). Smokers had a higher total mutational burden (TMB) (P = 0.01). Virus-positive patients had a lower TMB (P < 0.01) and improved OS (P = 0.02). Among virus-negative responders, NOTCH1 and SMARCA4 were more frequently mutated and frameshift events in tumor suppressor genes occurred more frequently (P = 0.03). Higher TMB and CD8+ T cell infiltrates predicted anti–PD-1/L1 benefit (P < 0.01, P < 0.01, respectively) among virus-negative tumors. TIM-3/LAG-3 coexpression with PD-1 was higher on T cells among nonresponders (P = 0.03 and 0.02, respectively). Somatic frameshift events in tumor suppressor genes and higher TMB among virus-negative SCCHN tumors predict anti–PD-1/L1 response.
Authors
Glenn J. Hanna, Patrick Lizotte, Megan Cavanaugh, Frank C. Kuo, Priyanka Shivdasani, Alexander Frieden, Nicole G. Chau, Jonathan D. Schoenfeld, Jochen H. Lorch, Ravindra Uppaluri, Laura E. MacConaill, Robert I. Haddad
Total citations by year
Citation information
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Differences in TCR repertoire and T cell activation underlie the divergent outcomes of antitumor immune responses in tumor-eradicating versus tumor-progressing hosts
RA Woolaver, X Wang, AL Krinsky, BC Waschke, SM Chen, V Popolizio, AG Nicklawsky, D Gao, Z Chen, A Jimeno, XJ Wang, JH Wang |
Journal for ImmunoTherapy of Cancer | 2021 |
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Neoadjuvant immunotherapy in resectable head and neck cancer: oral cavity carcinoma as a potential research model
VG Calderón, AC González, LG Carvajal, YA Lizarralde, AR Domínguez |
Therapeutic advances in medical oncology | 2021 |
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Prognostic and Predictive Factors in Advanced Head and Neck Squamous Cell Carcinoma
T Magnes, S Wagner, D Kiem, L Weiss, G Rinnerthaler, R Greil, T Melchardt |
International journal of molecular sciences | 2021 |
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Immunotherapy in Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck
RW Hsieh, S Borson, A Tsagianni, DP Zandberg |
Frontiers in Oncology | 2021 |
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ARID1A Mutation May Define an Immunologically Active Subgroup in Patients with Microsatellite Stable Colorectal Cancer
AM Sarshekeh, J Alshenaifi, J Roszik, GC Manyam, SM Advani, R Katkhuda, A Verma, M Lam, J Willis, JP Shen, J Morris, JS Davis, JM Loree, HM Lee, JA Ajani, DM Maru, MJ Overman, S Kopetz |
Clinical cancer research | 2021 |
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Pathogenic Role of Immune Evasion and Integration of Human Papillomavirus in Oropharyngeal Cancer
T Hatano, D Sano, H Takahashi, N Oridate |
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Novel Prognostic Score for recurrent or metastatic head and neck cancer patients treated with Nivolumab
K Minohara, T Matoba, D Kawakita, G Takano, K Oguri, A Murashima, K Nakai, S Iwaki, W Hojo, A Matsumura, S Ozaki, T Ozawa, I Harata, N Tanaka, S Maseki, H Tsuge, S Imaizumi, S Mitsuya, K Moribe, S Esaki, S Iwasaki |
Scientific Reports | 2021 |
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A Novel Immune-Related Prognostic Signature in Head and Neck Squamous Cell Carcinoma
Y Zhang, P Chen, Q Zhou, H Wang, Q Hua, J Wang, H Zhong |
Frontiers in Genetics | 2021 |
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Emerging role of SWI/SNF complex deficiency as a target of immune checkpoint blockade in human cancers
M Zhou, J Yuan, Y Deng, X Fan, J Shen |
Oncogenesis | 2021 |
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Positron Emission Tomography-Computed Tomography Parameters Predict Efficacy of Immunotherapy in Head and Neck Squamous Cell Carcinomas
S Zhang, R Zhang, W Gong, C Wang, C Zeng, Y Zhai, Q Fang, L Dai |
Frontiers in Oncology | 2021 |
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Immunotherapy for Head and Neck Cancer: A Paradigm Shift From Induction Chemotherapy to Neoadjuvant Immunotherapy
H Shibata, S Saito, R Uppaluri |
Frontiers in Oncology | 2021 |
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The Role of Oncogenes and Redox Signaling in the Regulation of PD-L1 in Cancer
C Glorieux, X Xia, P Huang |
Cancers | 2021 |
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Nivolumab in combination with cabozantinib for metastatic triple-negative breast cancer: a phase II and biomarker study
R Barroso-Sousa, TE Keenan, T Li, N Tayob, L Trippa, RG Pastorello, ET Richardson, D Dillon, Z Amoozgar, B Overmoyer, SJ Schnitt, EP Winer, EA Mittendorf, EV Allen, DG Duda, SM Tolaney |
npj Breast Cancer | 2021 |
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Recent Advances and Future Directions in Clinical Management of Head and Neck Squamous Cell Carcinoma
J Muzaffar, S Bari, K Kirtane, CH Chung |
Cancers | 2021 |
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miRNA-Based Signature Associated With Tumor Mutational Burden in Colon Adenocarcinoma
W Xue, Y Wang, Y Xie, C Yang, Z Gong, C Guan, C Wei, C Zhu, Z Niu |
Frontiers in Oncology | 2021 |
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PRF1 is a prognostic marker and correlated with immune infiltration in head and neck squamous cell carcinoma
C Fan, H Hu, Y Shen, Q Wang, Y Mao, B Ye, M Xiang |
Translational oncology | 2021 |
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Tumor microenvironment: an evil nexus promoting aggressive head and neck squamous cell carcinoma and avenue for targeted therapy
AA Bhat, P Yousuf, NA Wani, A Rizwan, SS Chauhan, MA Siddiqi, D Bedognetti, W El-Rifai, MP Frenneaux, SK Batra, M Haris, MA Macha |
Signal Transduction and Targeted Therapy | 2021 |
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Biomarkers of therapeutic response with immune checkpoint inhibitors
P Bindal, JE Gray, TA Boyle, V Florou, S Puri |
Annals of translational medicine | 2021 |
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Generation of triacyl lipopeptide-modified glycoproteins by metabolic glycoengineering as the neoantigen to boost anti-tumor immune response
Y Zhao, S Li, J Lv, Y Liu, Y Chen, Y Liu, X Chen, J Li, X Qin, X Wang, J Shi, Y Shi, R Xiang |
Theranostics | 2021 |
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Relationship between Tumor Mutational Burden, PD-L1, Patient Characteristics, and Response to Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinoma
KM Burcher, JW Lantz, E Gavrila, A Abreu, JT Burcher, AT Faucheux, A Xie, C Jackson, AH Song, RT Hughes, T Lycan, PM Bunch, CM Furdui, U Topaloglu, RB DAgostino, W Zhang, M Porosnicu |
Cancers | 2021 |
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Identification of factors related to immunotherapy efficacy and prognosis in patients with advanced head and neck squamous cell carcinoma
X Xu, R Li, L Zhang, G Zhu, D Ren, L Wu, X Gong |
Diagnostic Pathology | 2021 |
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Potential Biomarkers for the Efficacy of PD-1-PD-L Blockade in Cancer
M Grecea, O Soritau, D Dulf, TE Ciuleanu, M Zdrenghea |
OncoTargets and therapy | 2021 |
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Comprehensive Immunoprofiling of High-Risk Oral Proliferative and Localized Leukoplakia.
Hanna GJ, Villa A, Mistry N, Jia Y, Quinn CT, Turner MM, Felt KD, Pfaff K, Haddad RI, Uppaluri R, Rodig SJ, Woo SB, Egloff AM, Hodi FS |
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Radiomic analysis identifies tumor subtypes associated with distinct molecular and microenvironmental factors in head and neck squamous cell carcinoma
E Katsoulakis, Y Yu, AP Apte, JE Leeman, N Katabi, L Morris, JO Deasy, TA Chan, NY Lee, N Riaz, V Hatzoglou, JH Oh |
Oral Oncology | 2020 |
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Tumor mutation burden predicts response and survival to immune checkpoint inhibitors: a meta-analysis
L Wan, Z Wang, J Xue, H Yang, Y Zhu |
Translational cancer research | 2020 |
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Exploration of Feasible Immune Biomarkers for Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinoma Treatment in Real World Clinical Practice
HC Wang, TJ Yeh, LP Chan, CM Hsu, SF Cho |
International journal of molecular sciences | 2020 |
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The Evolving Landscape of PD-1/PD-L1 Pathway in Head and Neck Cancer
X Qiao, J Jiang, X Pang, M Huang, Y Tang, X Liang, Y Tang |
Frontiers in immunology | 2020 |
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Predictive biomarkers and mechanisms underlying resistance to PD1/PD-L1 blockade cancer immunotherapy
D Ren, Y Hua, B Yu, X Ye, Z He, C Li, J Wang, Y Mo, X Wei, Y Chen, Y Zhou, Q Liao, H Wang, B Xiang, M Zhou, X Li, G Li, Y Li, Z Zeng, W Xiong |
Molecular Cancer | 2020 |
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Role of DNA repair defects in predicting immunotherapy response
J Zhang, DJ Shih, SY Lin |
Biomarker Research | 2020 |
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MK Slevin, BM Wollison, W Powers, RT Burns, N Patel, MD Ducar, GJ Starrett, EP Garcia, DK Manning, J Cheng, GJ Hanna, KM Kaye, PV Hummelen, A Nag, AR Thorner, JA DeCaprio, LE MacConaill |
The Journal of molecular diagnostics : JMD | 2020 |
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Tumor Mutational Burden and PTEN Alterations as Molecular Correlates of Response to PD-1/L1 Blockade in Metastatic Triple-Negative Breast Cancer
R Barroso-Sousa, TE Keenan, S Pernas, P Exman, E Jain, AC Garrido-Castro, M Hughes, B Bychkovsky, R Umeton, JL Files, NI Lindeman, LE MacConaill, FS Hodi, IE Krop, D Dillon, EP Winer, N Wagle, NU Lin, EA Mittendorf, EM Allen, SM Tolaney |
Clinical cancer research | 2020 |
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Characterization of tumors with ultralow tumor mutational burden in Japanese cancer patients
K Hatakeyama, T Nagashima, K Ohshima, S Ohnami, S Ohnami, Y Shimoda, A Naruoka, K Maruyama, A Iizuka, T Ashizawa, T Mochizuki, K Urakami, Y Akiyama, K Yamaguchi |
Cancer Science | 2020 |
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Current Understanding of the Mechanisms Underlying Immune Evasion From PD-1/PD-L1 Immune Checkpoint Blockade in Head and Neck Cancer
VC Kok |
Frontiers in Oncology | 2020 |
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Natural Killer Cells as a Potential Biomarker for Predicting Immunotherapy Efficacy in Patients with Non-Small Cell Lung Cancer
YH Cho, MG Choi, DH Kim, YJ Choi, SY Kim, KJ Sung, JC Lee, SY Kim, JK Rho, CM Choi |
Targeted Oncology | 2020 |
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Tumor Mutational Burden as a Predictive Biomarker in Solid Tumors
D Sha, Z Jin, J Budczies, K Kluck, A Stenzinger, FA Sinicrope |
Cancer Discovery | 2020 |
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Genomics-based immuno-oncology: bridging the gap between immunology and tumor biology
RG DiNatale, AA Hakimi, TA Chan |
Human Molecular Genetics | 2020 |
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Clinical Efficacy and Molecular Response Correlates of the WEE1 Inhibitor Adavosertib Combined with Cisplatin in Patients with Metastatic Triple-Negative Breast Cancer
TE Keenan, T Li, T Vallius, JL Guerriero, N Tayob, B Kochupurakkal, J Davis, R Pastorello, RK Tahara, L Anderson, J Conway, MX He, E Shannon, RE Godin, PK Sorger, A D'Andrea, B Overmoyer, EP Winer, EA Mittendorf, EM Allen, GI Shapiro, SM Tolaney |
Clinical cancer research | 2020 |
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Association between APOBEC3H-Mediated Demethylation and Immune Landscape in Head and Neck Squamous Carcinoma
Q Liu, Y Luo, R Cao, X Pan, , S Zhang, W Zhang, J Zhou, B Cheng, X Ren |
BioMed Research International | 2020 |
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HPV Detection in Head and Neck Squamous Cell Carcinomas: What Is the Issue?
JG Augustin, C Lepine, A Morini, A Brunet, D Veyer, C Brochard, H Mirghani, H Péré, C Badoual |
Frontiers in Oncology | 2020 |
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PD-L1 Expression is Highly Associated with Tumor-Associated Macrophage Infiltration in Nasopharyngeal Carcinoma R Deng, J Lu, X Liu, XH Peng, J Wang, XP Li |
Cancer management and research | 2020 |
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Architectural Alterations in Oral Epithelial Dysplasia are Similar in Unifocal and Proliferative Leukoplakia
CC Li, S Almazrooa, I Carvo, A Salcines, SB Woo |
Head and Neck Pathology | 2020 |
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Hematological predictive markers for recurrent or metastatic squamous cell carcinomas of the head and neck treated with nivolumab: A multicenter study of 88 patients
T Matsuki, I Okamoto, C Fushimi, M Sawabe, D Kawakita, H Sato, K Tsukahara, T Kondo, T Okada, Y Tada, K Miura, G Omura, T Yamashita |
Cancer Medicine | 2020 |
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The Evolution of Care of Cancers of the Head and Neck Region: State of the Science in 2020
F Yan, HM Knochelmann, PF Morgan, JM Kaczmar, DM Neskey, EM Graboyes, SA Nguyen, B Ogretmen, AK Sharma, TA Day |
Cancers | 2020 |
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Predictive biomarkers for cancer immunotherapy with immune checkpoint inhibitors
R Bai, Z Lv, D Xu, J Cui |
Biomarker Research | 2020 |
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Immunotherapy Breakthroughs in the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
C Borel, AC Jung, M Burgy |
Cancers | 2020 |
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NOTCH1 Signaling in Head and Neck Squamous Cell Carcinoma
PA Shah, C Huang, Q Li, SA Kazi, LA Byers, J Wang, FM Johnson, MJ Frederick |
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Tumor microenvironment characterization in head and neck cancer identifies prognostic and immunotherapeutically relevant gene signatures
M Huo, Y Zhang, Z Chen, S Zhang, Y Bao, T Li |
Scientific Reports | 2020 |
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In silico analysis reveals EP300 as a panCancer inhibitor of anti-tumor immune response via metabolic modulation
R Krupar, C Watermann, C Idel, J Ribbat-Idel, A Offermann, H Pasternack, J Kirfel, AG Sikora, S Perner |
Scientific Reports | 2020 |
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Age and Mutations as Predictors of the Response to Immunotherapy in Head and Neck Squamous Cell Cancer
Y Zhang, A Lin, Y Li, W Ding, H Meng, P Luo, J Zhang |
Frontiers in Cell and Developmental Biology | 2020 |
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Genetic Ancestry Contributes to Somatic Mutations in Lung Cancers from Admixed Latin American Populations
J Carrot-Zhang, G Soca-Chafre, N Patterson, AR Thorner, A Nag, J Watson, G Genovese, J Rodriguez, MK Gelbard, L Corrales-Rodriguez, Y Mitsuishi, G Ha, JD Campbell, GR Oxnard, O Arrieta, AF Cardona, A Gusev, M Meyerson |
Cancer Discovery | 2020 |
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Effect of Eribulin With or Without Pembrolizumab on Progression-Free Survival for Patients With Hormone Receptor–Positive, ERBB2 -Negative Metastatic Breast Cancer: A Randomized Clinical Trial
SM Tolaney, R Barroso-Sousa, T Keenan, T Li, L Trippa, I Vaz-Luis, G Wulf, L Spring, NF Sinclair, C Andrews, J Pittenger, ET Richardson, D Dillon, NU Lin, B Overmoyer, AH Partridge, EV Allen, EA Mittendorf, EP Winer, IE Krop |
JAMA Oncology | 2020 |
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Biomarkers of Immune Checkpoint Inhibitor Efficacy in Cancer
DE Meyers, S Banerji |
Current Oncology | 2020 |
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Targeting the Immune Microenvironment in the Treatment of Head and Neck Squamous Cell Carcinoma
HC Wang, LP Chan, SF Cho |
Frontiers in Oncology | 2019 |
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Conceptual Development of Immunotherapeutic Approaches to Gastrointestinal Cancer
BA Abolarinwa, RB Ibrahim, YH Huang |
International journal of molecular sciences | 2019 |
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The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy
JJ Havel, D Chowell, TA Chan |
Nature Reviews Cancer | 2019 |
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Heterogeneity of the Head and Neck Squamous Cell Carcinoma Immune Landscape and Its Impact on Immunotherapy
M Canning, G Guo, M Yu, C Myint, MW Groves, JK Byrd, Y Cui |
Frontiers in Cell and Developmental Biology | 2019 |
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Immunotherapies and Future Combination Strategies for Head and Neck Squamous Cell Carcinoma
V Cristina, RG Herrera-Gómez, P Szturz, V Espeli, M Siano |
International journal of molecular sciences | 2019 |
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Rationale of Immunotherapy in Hepatocellular Carcinoma and Its Potential Biomarkers
D Tai, SP Choo, V Chew |
Cancers | 2019 |
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Intramuscular fast-flow vascular anomaly contains somatic MAP2K1 and KRAS mutations
JA Goss, DJ Konczyk, PJ Smits, HP Kozakewich, AI Alomari, A Al-Ibraheemi, AH Taghinia, BH Dickie, DM Adams, SJ Fishman, JB Mulliken, ML Warman, AK Greene |
Angiogenesis | 2019 |
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Prognostic value of the association between MHC class I downregulation and PD-L1 upregulation in head and neck squamous cell carcinoma patients
SH Yoo, B Keam, CY Ock, S Kim, B Han, JW Kim, KW Lee, YK Jeon, KC Jung, EJ Chung, SK Kwon, SH Ahn, MW Sung, DS Heo |
Scientific Reports | 2019 |
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Immune checkpoint inhibitors in the treatment of virus-associated cancers
P Gao, C Lazare, C Cao, Y Meng, P Wu, W Zhi, S Lin, J Wei, X Huang, , G Chen, J Hu, D Ma, P Wu |
Journal of Hematology & Oncology | 2019 |
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High tumor mutation burden predicts better efficacy of immunotherapy: a pooled analysis of 103078 cancer patients
D Cao, H Xu, X Xu, T Guo, W Ge |
OncoImmunology | 2019 |
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Efficacy and biomarker analysis of nivolumab plus gemcitabine and cisplatin in patients with unresectable or metastatic biliary tract cancers: results from a phase II study
K Feng, Y Liu, Y Zhao, Q Yang, L Dong, J Liu, X Li, Z Zhao, Q Mei, W Han |
Journal for ImmunoTherapy of Cancer | 2019 |
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The Mutational Landscape of Recurrent vs Non-Recurrent Human Papillomavirus-Related Oropharyngeal Cancer
Richard Harbison, Mark Kubik, Eric Konnick, Qing Zhang, Seok-Geun Lee, Heuijoon Park, Jianan Zhang, Christopher Carlson, Chu Chen, Stephen Schwartz, Cristina Rodriguez, Umamaheswar Duvvuri, Eduardo Mendez |
JCI Insight | 2018 |
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Improved outcomes in PI3K pathway altered metastatic HPV oropharyngeal cancer
Glenn J Hanna, Alec Kacew, Nicole Grace Chau, Priyanka Shivdasani, Jochen Lorch, Ravindra Uppaluri, Robert Haddad, Laura MacConaill |
JCI Insight | 2018 |
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Immune biomarkers of response to immune-checkpoint inhibitors in head and neck squamous cell carcinoma
M Oliva, A Spreafico, M Taberna, L Alemany, B Coburn, R Mesia, LL Siu |
Annals of Oncology | 2018 |
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Immunogenomic Landscape Contributes to Hyperprogressive Disease after Anti-PD-1 Immunotherapy for Cancer
D Xiong, Y Wang, AK Singavi, AC Mackinnon, B George, M You |
iScience | 2018 |
