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Title:
Analysis of tumor-infiltrating CD103 resident memory T-cell content in recurrent laryngeal squamous cell carcinoma | Cancer Immunology, Immunotherapy
Description:
Background Recurrent laryngeal squamous cell carcinomas (LSCCs) are associated with poor outcomes, without reliable biomarkers to identify patients who may benefit from adjuvant therapies. Given the emergence of tumor-infiltrating lymphocytes (TIL) as a biomarker in head and neck squamous cell carcinoma, we generated predictive models to understand the utility of CD4+, CD8+ and/or CD103+ TIL status in patients with advanced LSCC. Methods Tissue microarrays were constructed from salvage laryngectomy specimens of 183 patients with recurrent/persistent LSCC and independently stained for CD4+, CD8+, and CD103+ TIL content. Cox proportional hazards regression analysis was employed to assess combinations of CD4+, CD8+, and CD103+ TIL levels for prediction of overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) in patients with recurrent/persistent LSCC. Results High tumor CD103+ TIL content was associated with significantly improved OS, DSS, and DFS and was a stronger predictor of survival in recurrent/persistent LSCC than either high CD8+ or CD4+ TIL content. On multivariate analysis, an “immune-rich” phenotype, in which tumors were enriched for both CD103+ and CD4+ TILs, conferred a survival benefit (OS hazard ratio: 0.28, p = 0.0014; DSS hazard ratio: 0.09, p = 0.0015; DFS hazard ratio: 0.18, p = 0.0018) in recurrent/persistent LSCC. Conclusions An immune profile driven by CD103+ TIL content, alone and in combination with CD4+ TIL content, is a prognostic biomarker of survival in patients with recurrent/persistent LSCC. Predictive models described herein may thus prove valuable in prognostic stratification and lead to personalized treatment paradigms for this patient population.
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Keywords {🔍}
article, pubmed, cancer, google, scholar, cell, squamous, head, neck, cas, carcinoma, survival, content, central, laryngeal, patients, til, lymphocytes, oncol, university, michigan, analysis, thomas, chad, brenner, tumor, infiltrating, ann, usa, mann, lscc, cells, arbor, tumorinfiltrating, birkeland, wolf, matthew, spector, recurrentpersistent, prognostic, clin, oral, department, privacy, cookies, memory, jacqueline, smith, andrew, bellile,
Topics {✒️}
tissue-resident memory features month download article/chapter tumor-infiltrating lymphocytes expressing small-cell lung cancer nih grants u01-de025184 nih grant f31-de02760001 nih grant t32-dc535615 american joint committee article cancer immunology related subjects tumor-infiltrating lymphocytes tumor infiltrating lymphocytes cd1a-positive dendritic cells tumor-infiltrating lymphocyte full article pdf advanced laryngeal cancer tumor-infiltrating regulatory recurrent/persistent lscc immune profile driven privacy choices/manage cookies advanced larynx cancer human ovarian cancer cd103+ til content long-term results human lung cancer prognostic markers cd103+ til status cd103+ til levels neck cancer identifies salvage laryngectomy specimens medical center dr tumor lymphocytic infiltration neck spore program disease-specific survival disease-free survival infiltrating lymphocytes pd-l1+ european economic area os hazard ratio personalized treatment paradigms nonsurgical treatment strategies biologically distinct hpv cutpoint determination methods copy number alterations jbm ensured quality ethics declarations conflict �immune-rich” phenotype carey received funding smith received funding conditions privacy policy
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headline:Analysis of tumor-infiltrating CD103 resident memory T-cell content in recurrent laryngeal squamous cell carcinoma
description:Recurrent laryngeal squamous cell carcinomas (LSCCs) are associated with poor outcomes, without reliable biomarkers to identify patients who may benefit from adjuvant therapies. Given the emergence of tumor-infiltrating lymphocytes (TIL) as a biomarker in head and neck squamous cell carcinoma, we generated predictive models to understand the utility of CD4+, CD8+ and/or CD103+ TIL status in patients with advanced LSCC. Tissue microarrays were constructed from salvage laryngectomy specimens of 183 patients with recurrent/persistent LSCC and independently stained for CD4+, CD8+, and CD103+ TIL content. Cox proportional hazards regression analysis was employed to assess combinations of CD4+, CD8+, and CD103+ TIL levels for prediction of overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) in patients with recurrent/persistent LSCC. High tumor CD103+ TIL content was associated with significantly improved OS, DSS, and DFS and was a stronger predictor of survival in recurrent/persistent LSCC than either high CD8+ or CD4+ TIL content. On multivariate analysis, an “immune-rich” phenotype, in which tumors were enriched for both CD103+ and CD4+ TILs, conferred a survival benefit (OS hazard ratio: 0.28, p = 0.0014; DSS hazard ratio: 0.09, p = 0.0015; DFS hazard ratio: 0.18, p = 0.0018) in recurrent/persistent LSCC. An immune profile driven by CD103+ TIL content, alone and in combination with CD4+ TIL content, is a prognostic biomarker of survival in patients with recurrent/persistent LSCC. Predictive models described herein may thus prove valuable in prognostic stratification and lead to personalized treatment paradigms for this patient population.
datePublished:2018-10-25T00:00:00Z
dateModified:2018-10-25T00:00:00Z
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keywords:
CD103
Resident memory
T-cell
HNSCC
Larynx
Oncology
Immunology
Cancer Research
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headline:Analysis of tumor-infiltrating CD103 resident memory T-cell content in recurrent laryngeal squamous cell carcinoma
description:Recurrent laryngeal squamous cell carcinomas (LSCCs) are associated with poor outcomes, without reliable biomarkers to identify patients who may benefit from adjuvant therapies. Given the emergence of tumor-infiltrating lymphocytes (TIL) as a biomarker in head and neck squamous cell carcinoma, we generated predictive models to understand the utility of CD4+, CD8+ and/or CD103+ TIL status in patients with advanced LSCC. Tissue microarrays were constructed from salvage laryngectomy specimens of 183 patients with recurrent/persistent LSCC and independently stained for CD4+, CD8+, and CD103+ TIL content. Cox proportional hazards regression analysis was employed to assess combinations of CD4+, CD8+, and CD103+ TIL levels for prediction of overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) in patients with recurrent/persistent LSCC. High tumor CD103+ TIL content was associated with significantly improved OS, DSS, and DFS and was a stronger predictor of survival in recurrent/persistent LSCC than either high CD8+ or CD4+ TIL content. On multivariate analysis, an “immune-rich” phenotype, in which tumors were enriched for both CD103+ and CD4+ TILs, conferred a survival benefit (OS hazard ratio: 0.28, p = 0.0014; DSS hazard ratio: 0.09, p = 0.0015; DFS hazard ratio: 0.18, p = 0.0018) in recurrent/persistent LSCC. An immune profile driven by CD103+ TIL content, alone and in combination with CD4+ TIL content, is a prognostic biomarker of survival in patients with recurrent/persistent LSCC. Predictive models described herein may thus prove valuable in prognostic stratification and lead to personalized treatment paradigms for this patient population.
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dateModified:2018-10-25T00:00:00Z
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pageEnd:220
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CD103
Resident memory
T-cell
HNSCC
Larynx
Oncology
Immunology
Cancer Research
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type:PostalAddress
type:Organization
name:Steven B. Chinn
affiliation:
name:University of Michigan
address:
name:Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, USA
type:PostalAddress
type:Organization
name:Andrew G. Shuman
affiliation:
name:University of Michigan
address:
name:Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, USA
type:PostalAddress
type:Organization
name:Kelly M. Malloy
affiliation:
name:University of Michigan
address:
name:Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, USA
type:PostalAddress
type:Organization
name:Keith A. Casper
affiliation:
name:University of Michigan
address:
name:Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, USA
type:PostalAddress
type:Organization
name:Scott A. McLean
affiliation:
name:University of Michigan
address:
name:Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, USA
type:PostalAddress
type:Organization
name:Jeffery S. Moyer
affiliation:
name:University of Michigan
address:
name:Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, USA
type:PostalAddress
type:Organization
name:Gregory T. Wolf
affiliation:
name:University of Michigan
address:
name:Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, USA
type:PostalAddress
type:Organization
name:University of Michigan
address:
name:Rogel Cancer Center, University of Michigan, Ann Arbor, USA
type:PostalAddress
type:Organization
name:Carol R. Bradford
affiliation:
name:University of Michigan
address:
name:Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, USA
type:PostalAddress
type:Organization
name:University of Michigan
address:
name:Rogel Cancer Center, University of Michigan, Ann Arbor, USA
type:PostalAddress
type:Organization
name:Mark E. Prince
affiliation:
name:University of Michigan
address:
name:Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, USA
type:PostalAddress
type:Organization
name:University of Michigan
address:
name:Rogel Cancer Center, University of Michigan, Ann Arbor, USA
type:PostalAddress
type:Organization
name:Thomas E. Carey
affiliation:
name:University of Michigan
address:
name:Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, USA
type:PostalAddress
type:Organization
name:University of Michigan
address:
name:Rogel Cancer Center, University of Michigan, Ann Arbor, USA
type:PostalAddress
type:Organization
name:University of Michigan
address:
name:Department of Pharmacology, University of Michigan, Ann Arbor, USA
type:PostalAddress
type:Organization
name:Jonathan B. McHugh
affiliation:
name:University of Michigan
address:
name:Department of Pathology, University of Michigan, Ann Arbor, USA
type:PostalAddress
type:Organization
name:University of Michigan
address:
name:Rogel Cancer Center, University of Michigan, Ann Arbor, USA
type:PostalAddress
type:Organization
name:Matthew E. Spector
affiliation:
name:University of Michigan
address:
name:Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, USA
type:PostalAddress
type:Organization
name:University of Michigan
address:
name:Rogel Cancer Center, University of Michigan, Ann Arbor, USA
type:PostalAddress
type:Organization
email:[email protected]
name:J. Chad Brenner
affiliation:
name:University of Michigan
address:
name:Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, USA
type:PostalAddress
type:Organization
name:University of Michigan
address:
name:Rogel Cancer Center, University of Michigan, Ann Arbor, USA
type:PostalAddress
type:Organization
name:University of Michigan
address:
name:Department of Pharmacology, University of Michigan, Ann Arbor, USA
type:PostalAddress
type:Organization
email:[email protected]
PostalAddress:
name:Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, USA
name:Department of Pathology, University of Michigan, Ann Arbor, USA
name:Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, USA
name:Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, USA
name:Department of Biostatistics, University of Michigan, Ann Arbor, USA
name:Department of Hematology and Oncology, University of Michigan, Ann Arbor, USA
name:Department of Radiation Oncology, University of Michigan, Ann Arbor, USA
name:Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, USA
name:Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, USA
name:Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, USA
name:Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, USA
name:Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, USA
name:Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, USA
name:Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, USA
name:Rogel Cancer Center, University of Michigan, Ann Arbor, USA
name:Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, USA
name:Rogel Cancer Center, University of Michigan, Ann Arbor, USA
name:Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, USA
name:Rogel Cancer Center, University of Michigan, Ann Arbor, USA
name:Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, USA
name:Rogel Cancer Center, University of Michigan, Ann Arbor, USA
name:Department of Pharmacology, University of Michigan, Ann Arbor, USA
name:Department of Pathology, University of Michigan, Ann Arbor, USA
name:Rogel Cancer Center, University of Michigan, Ann Arbor, USA
name:Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, USA
name:Rogel Cancer Center, University of Michigan, Ann Arbor, USA
name:Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, USA
name:Rogel Cancer Center, University of Michigan, Ann Arbor, USA
name:Department of Pharmacology, University of Michigan, Ann Arbor, USA
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