Analysis of tumor-infiltrating CD103 resident memory T-cell content in recurrent laryngeal squamous cell carcinoma

Jacqueline E. Mann, Joshua D. Smith, Andrew C. Birkeland, Emily Bellile, Paul Swiecicki, Michelle Mierzwa, Steven B. Chinn, Andrew G. Shuman, Kelly M. Malloy, Keith A. Casper, Scott A. McLean, Jeffery S. Moyer, Gregory T. Wolf, Carol R. Bradford, Mark E. Prince, Thomas E. Carey, Jonathan B. McHugh, Matthew E. Spector, J. Chad Brenner

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)213-220
Number of pages8
JournalCancer Immunology, Immunotherapy
Volume68
Issue number2
DOIs
StatePublished - Feb 13 2019
Externally publishedYes

Fingerprint

Tumor-Infiltrating Lymphocytes
Squamous Cell Carcinoma
T-Lymphocytes
Survival
Neoplasms
Disease-Free Survival
Biomarkers
Laryngectomy
Multivariate Analysis
Regression Analysis
Phenotype

Keywords

  • CD103
  • HNSCC
  • Larynx
  • Resident memory
  • T-cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

Cite this

Analysis of tumor-infiltrating CD103 resident memory T-cell content in recurrent laryngeal squamous cell carcinoma. / Mann, Jacqueline E.; Smith, Joshua D.; Birkeland, Andrew C.; Bellile, Emily; Swiecicki, Paul; Mierzwa, Michelle; Chinn, Steven B.; Shuman, Andrew G.; Malloy, Kelly M.; Casper, Keith A.; McLean, Scott A.; Moyer, Jeffery S.; Wolf, Gregory T.; Bradford, Carol R.; Prince, Mark E.; Carey, Thomas E.; McHugh, Jonathan B.; Spector, Matthew E.; Brenner, J. Chad.

In: Cancer Immunology, Immunotherapy, Vol. 68, No. 2, 13.02.2019, p. 213-220.

Research output: Contribution to journalArticle

Mann, JE, Smith, JD, Birkeland, AC, Bellile, E, Swiecicki, P, Mierzwa, M, Chinn, SB, Shuman, AG, Malloy, KM, Casper, KA, McLean, SA, Moyer, JS, Wolf, GT, Bradford, CR, Prince, ME, Carey, TE, McHugh, JB, Spector, ME & Brenner, JC 2019, 'Analysis of tumor-infiltrating CD103 resident memory T-cell content in recurrent laryngeal squamous cell carcinoma', Cancer Immunology, Immunotherapy, vol. 68, no. 2, pp. 213-220. https://doi.org/10.1007/s00262-018-2256-3
Mann, Jacqueline E. ; Smith, Joshua D. ; Birkeland, Andrew C. ; Bellile, Emily ; Swiecicki, Paul ; Mierzwa, Michelle ; Chinn, Steven B. ; Shuman, Andrew G. ; Malloy, Kelly M. ; Casper, Keith A. ; McLean, Scott A. ; Moyer, Jeffery S. ; Wolf, Gregory T. ; Bradford, Carol R. ; Prince, Mark E. ; Carey, Thomas E. ; McHugh, Jonathan B. ; Spector, Matthew E. ; Brenner, J. Chad. / Analysis of tumor-infiltrating CD103 resident memory T-cell content in recurrent laryngeal squamous cell carcinoma. In: Cancer Immunology, Immunotherapy. 2019 ; Vol. 68, No. 2. pp. 213-220.
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abstract = "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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T1 - Analysis of tumor-infiltrating CD103 resident memory T-cell content in recurrent laryngeal squamous cell carcinoma

AU - Mann, Jacqueline E.

AU - Smith, Joshua D.

AU - Birkeland, Andrew C.

AU - Bellile, Emily

AU - Swiecicki, Paul

AU - Mierzwa, Michelle

AU - Chinn, Steven B.

AU - Shuman, Andrew G.

AU - Malloy, Kelly M.

AU - Casper, Keith A.

AU - McLean, Scott A.

AU - Moyer, Jeffery S.

AU - Wolf, Gregory T.

AU - Bradford, Carol R.

AU - Prince, Mark E.

AU - Carey, Thomas E.

AU - McHugh, Jonathan B.

AU - Spector, Matthew E.

AU - Brenner, J. Chad

PY - 2019/2/13

Y1 - 2019/2/13

N2 - 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.

AB - 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.

KW - CD103

KW - HNSCC

KW - Larynx

KW - Resident memory

KW - T-cell

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