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Abstract
Evaluation of T lymphocyte frequency provides prognostic information for patients with oral squamous cell cancer (OSCC). However, the effect of simultaneously evaluating T cell frequency and assessing suppressive elements and defects in antigen-processing machinery (APM) has not been clarified. Simultaneous characterization of CD3+, CD8+, FoxP3+, CD163+, and PD-L1+ cells using multispectral imaging was performed on sections from 119 patients with HPV– OSCC. Expression of β2-microglobulin, MHC class I heavy chain, and large multifunctional peptidase 10 was quantified, and all data were correlated with patient outcome. We found that, consistent with previous reports, high numbers of CD8+ T cells at the invasive margin correlated significantly with prolonged overall survival (OS), while the number of FoxP3+ or PD-L1+ cells did not. Compiling the number of FoxP3+ or PD-L1+ cells within 30 μm of CD8+ T cells identified a significant association with a high number of suppressive elements close to CD8+ T cells and reduced OS. Integrating this information into a cumulative suppression index (CSI) increased correlation with OS. Incorporating tumor expression levels of APM components with CSI further improved prognostic power. This multiparametric immune profiling may be useful for stratifying patients with OSCC for clinical trials.
Authors
Zipei Feng, Daniel Bethmann, Matthias Kappler, Carmen Ballesteros-Merino, Alexander Eckert, R. Bryan Bell, Allen Cheng, Tuan Bui, Rom Leidner, Walter J. Urba, Kent Johnson, Clifford Hoyt, Carlo B. Bifulco, Juergen Bukur, Claudia Wickenhauser, Barbara Seliger, Bernard A. Fox
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Citations to this article (105)
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The role of Ki-67 in Asian triple negative breast cancers: a novel combinatory panel approach
AS Tan, JP Yeong, CP Lai, CH Ong, B Lee, JC Lim, AA Thike, J Iqbal, RA Dent, EH Lim, PH Tan |
Virchows Archiv | 2019 |
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Targeting EZH2 Enhances Antigen Presentation, Antitumor Immunity, and Circumvents Anti–PD-1 Resistance in Head and Neck Cancer
L Zhou, T Mudianto, X Ma, R Riley, R Uppaluri |
Clinical cancer research | 2019 |
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Spatial proximity between T and PD-L1 expressing cells as a prognostic biomarker for oropharyngeal squamous cell carcinoma
AM Tsakiroglou, M Fergie, K Oguejiofor, K Linton, D Thomson, PL Stern, S Astley, R Byers, CM West |
British Journal of Cancer | 2019 |
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Spatial and phenotypic immune profiling of metastatic colon cancer
Jenny Lazarus, Tomek Maj, J. Joshua Smith, Mirna Perusina Lanfranca, Arvind Rao, Michael D'Angelica, Lawrence Delrosario, Alexander Girgis, Casey Schukow, Jinru Shia, Ilona Kryczek, Jiaqi Shi, Isaac Wasserman, Howard Crawford, Hari Nathan, Marina Pasca di Magliano, Weiping Zou, Timothy L Frankel |
JCI Insight | 2018 |
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Perspectives in immunotherapy: meeting report from the Immunotherapy Bridge (29-30 November, 2017, Naples, Italy)
PA Ascierto, J Brugarolas, L Buonaguro, LH Butterfield, D Carbone, B Daniele, R Ferris, BA Fox, J Galon, C Gridelli, HL Kaufman, CA Klebanoff, I Melero, P Nathan, CM Paulos, M Ruella, R Sullivan, H Zarour, I Puzanov |
Journal for ImmunoTherapy of Cancer | 2018 |
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Treatment-naïve HPV+ head and neck cancers display a T-cell-inflamed phenotype distinct from their HPV- counterparts that has implications for immunotherapy
SF Gameiro, F Ghasemi, JW Barrett, J Koropatnick, AC Nichols, JS Mymryk, SM Vareki |
OncoImmunology | 2018 |
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On the Road to Immunotherapy—Prospects for Treating Head and Neck Cancers With Checkpoint Inhibitor Antibodies
FJ Ward, LN Dahal, R Abu-Eid |
Frontiers in immunology | 2018 |
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Machine Learning Methods for Histopathological Image Analysis
D Komura, S Ishikawa |
Computational and Structural Biotechnology Journal | 2018 |
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Measuring multiple parameters of CD8+ tumor-infiltrating lymphocytes in human cancers by image analysis
KE Steele, TH Tan, R Korn, K Dacosta, C Brown, M Kuziora, J Zimmermann, B Laffin, M Widmaier, L Rognoni, R Cardenes, K Schneider, A Boutrin, P Martin, J Zha, T Wiestler |
Journal for ImmunoTherapy of Cancer | 2018 |
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The Prognostic Value of Immune Factors in the Tumor Microenvironment of Penile Squamous Cell Carcinoma
SR Ottenhof, RS Djajadiningrat, HH Thygesen, PJ Jakobs, K Jóźwiak, AM Heeren, J de Jong, J Sanders, S Horenblas, ES Jordanova |
Frontiers in immunology | 2018 |
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Quantitative Analysis of Immune Infiltrates in Primary Melanoma
RD Gartrell, DK Marks, TD Hart, Li, DR Davari, A Wu, Z Blake, Y Lu, KN Askin, A Monod, CL Esancy, EC Stack, DT Jia, PM Armenta, Y Fu, D Izaki, B Taback, R Rabadan, HL Kaufman, CG Drake, BA Horst, YM Saenger |
Cancer immunology research | 2018 |
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Utility of CD8 score by automated quantitative image analysis in head and neck squamous cell carcinoma
DJ Hartman, F Ahmad, RE Ferris, D Rimm, L Pantanowitz |
Oral Oncology | 2018 |
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Multidimensional, quantitative assessment of PD-1/PD-L1 expression in patients with Merkel cell carcinoma and association with response to pembrolizumab
NA Giraldo, P Nguyen, EL Engle, GJ Kaunitz, TR Cottrell, S Berry, B Green, A Soni, JD Cuda, JE Stein, JC Sunshine, F Succaria, H Xu, A Ogurtsova, L Danilova, CD Church, NJ Miller, S Fling, L Lundgren, N Ramchurren, JH Yearley, EJ Lipson, M Cheever, RA Anders, PT Nghiem, SL Topalian, JM Taube |
Journal for ImmunoTherapy of Cancer | 2018 |
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Deciphering the Role of Regulatory CD4 T Cells in Oral and Oropharyngeal Cancer: A Systematic Review
C O'Higgins, FJ Ward, RA Eid |
Frontiers in Oncology | 2018 |
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Role of the immunosuppressive microenvironment in immunotherapy
GW Tormoen, MR Crittenden, MJ Gough |
Advances in Radiation Oncology | 2018 |
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Precision immunoprofiling by image analysis and artificial intelligence
VH Koelzer, K Sirinukunwattana, J Rittscher, KD Mertz |
Virchows Archiv | 2018 |
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HLA class II expression on tumor cells and low numbers of tumor‐associated macrophages predict clinical outcome in oropharyngeal cancer
B Cioni, ES Jordanova, E Hooijberg, R Linden, RX Menezes, K Tan, S Willems, JB Elbers, A Broeks, AM Bergman, CL Zuur, JP de Boer |
Head & neck | 2018 |
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Implantable biomaterials to provide local immunotherapy following surgical resection
MJ Gough, JR Baird, RB Bell |
Oncotarget | 2018 |
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Novel frontiers in detecting cancer metastasis
SP Leong, C Ballesteros-Merino, SM Jensen, S Marwitz, C Bifulco, BA Fox, M Skoberne |
Clinical & Experimental Metastasis | 2018 |
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The TAM family as a therapeutic target in combination with radiation therapy
FM Marincola, GW Tormoen, MR Crittenden, MJ Gough |
Emerging Topics in Life Sciences | 2017 |
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Pulmonary surfactant: an immunological perspective
ZC Chroneos, Z Sever-Chroneos, VL Shepherd |
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology | 2009 |
