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Digital pathology-aided assessment of tumor-infiltrating T lymphocytes in advanced stage, HPV-negative head and neck tumors.
Cancer Immunol Immunother. 2020 Apr; 69(4):581-591.CI

Abstract

AIM

This study aimed to evaluate the presence and prognostic value of tumor-infiltrating T cells in the tumor epithelium in advanced stage, HPV-negative head and neck squamous cell carcinoma (HNSCC) patients treated with primary chemoradiotherapy using digital pathology.

METHODS

Pre-treatment biopsies from 80 oropharyngeal, 52 hypopharyngeal, and 29 laryngeal cancer patients were collected in a tissue microarray (TMA) and immunohistochemically stained for T-cell markers CD3, CD4, CD8, FoxP3, and PD1, and for immune checkpoint PD-L1. For each marker, the number of positive tumor-infiltrating lymphocytes (TILs) per mm2 tumor epithelium was digitally quantified and correlated to overall survival (OS), disease-free survival (DFS), and locoregional control (LRC), as well as to clinicopathological characteristics. Differences in clinical outcome were estimated using Cox proportional hazard analysis and visualized using Kaplan-Meier curves.

RESULTS

The patient cohort had a 3-year OS of 58%, with a median follow-up of 53 months. None of the T-cell markers showed a correlation with OS, DFS or LRC. A low N stage was correlated to a better prognosis (OS: HR 0.39, p = 0.0028, DFS: HR 0.34, p = < 0.001, LRC: HR 0.24, p = 0.008). High TIL counts were more often observed in PD-L1-positive tumors (p < 0.05).

CONCLUSION

This study showed an objective, digital pathology-aided method to assess TILs in the tumor epithelium. However, it did not provide evidence for a prognostic role of the presence of CD3 + , CD4 + , CD8 + , FoxP3 + , and PD1 + TILs in the tumor epithelium of advanced stage, HPV-negative HNSCC patients treated with primary chemoradiotherapy.

Authors+Show Affiliations

Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. e.j.deruiter-2@umcutrecht.nl.Department of Otolaryngology/Head and Neck Surgery, Cancer Center Amsterdam, Amsterdam University Medical Center, Amsterdam, The Netherlands.Department of Otolaryngology/Head and Neck Surgery, Cancer Center Amsterdam, Amsterdam University Medical Center, Amsterdam, The Netherlands.Department of Otolaryngology/Head and Neck Surgery, Cancer Center Amsterdam, Amsterdam University Medical Center, Amsterdam, The Netherlands.Department of Head and Neck Surgical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.Department of Radiotherapy, University Medical Center Utrecht, Utrecht, The Netherlands.Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31980916

Citation

de Ruiter, Emma J., et al. "Digital Pathology-aided Assessment of Tumor-infiltrating T Lymphocytes in Advanced Stage, HPV-negative Head and Neck Tumors." Cancer Immunology, Immunotherapy : CII, vol. 69, no. 4, 2020, pp. 581-591.
de Ruiter EJ, de Roest RH, Brakenhoff RH, et al. Digital pathology-aided assessment of tumor-infiltrating T lymphocytes in advanced stage, HPV-negative head and neck tumors. Cancer Immunol Immunother. 2020;69(4):581-591.
de Ruiter, E. J., de Roest, R. H., Brakenhoff, R. H., Leemans, C. R., de Bree, R., Terhaard, C. H. J., & Willems, S. M. (2020). Digital pathology-aided assessment of tumor-infiltrating T lymphocytes in advanced stage, HPV-negative head and neck tumors. Cancer Immunology, Immunotherapy : CII, 69(4), 581-591. https://doi.org/10.1007/s00262-020-02481-3
de Ruiter EJ, et al. Digital Pathology-aided Assessment of Tumor-infiltrating T Lymphocytes in Advanced Stage, HPV-negative Head and Neck Tumors. Cancer Immunol Immunother. 2020;69(4):581-591. PubMed PMID: 31980916.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Digital pathology-aided assessment of tumor-infiltrating T lymphocytes in advanced stage, HPV-negative head and neck tumors. AU - de Ruiter,Emma J, AU - de Roest,Reinout H, AU - Brakenhoff,Ruud H, AU - Leemans,C René, AU - de Bree,Remco, AU - Terhaard,Chris H J, AU - Willems,Stefan M, Y1 - 2020/01/24/ PY - 2019/08/14/received PY - 2020/01/04/accepted PY - 2020/1/26/pubmed PY - 2020/4/21/medline PY - 2020/1/26/entrez KW - Head and neck squamous cell carcinoma (HNSCC) KW - Prognostic biomarkers KW - T cells KW - Tumor-infiltrating lymphocytes (TILs) SP - 581 EP - 591 JF - Cancer immunology, immunotherapy : CII JO - Cancer Immunol Immunother VL - 69 IS - 4 N2 - AIM: This study aimed to evaluate the presence and prognostic value of tumor-infiltrating T cells in the tumor epithelium in advanced stage, HPV-negative head and neck squamous cell carcinoma (HNSCC) patients treated with primary chemoradiotherapy using digital pathology. METHODS: Pre-treatment biopsies from 80 oropharyngeal, 52 hypopharyngeal, and 29 laryngeal cancer patients were collected in a tissue microarray (TMA) and immunohistochemically stained for T-cell markers CD3, CD4, CD8, FoxP3, and PD1, and for immune checkpoint PD-L1. For each marker, the number of positive tumor-infiltrating lymphocytes (TILs) per mm2 tumor epithelium was digitally quantified and correlated to overall survival (OS), disease-free survival (DFS), and locoregional control (LRC), as well as to clinicopathological characteristics. Differences in clinical outcome were estimated using Cox proportional hazard analysis and visualized using Kaplan-Meier curves. RESULTS: The patient cohort had a 3-year OS of 58%, with a median follow-up of 53 months. None of the T-cell markers showed a correlation with OS, DFS or LRC. A low N stage was correlated to a better prognosis (OS: HR 0.39, p = 0.0028, DFS: HR 0.34, p = < 0.001, LRC: HR 0.24, p = 0.008). High TIL counts were more often observed in PD-L1-positive tumors (p < 0.05). CONCLUSION: This study showed an objective, digital pathology-aided method to assess TILs in the tumor epithelium. However, it did not provide evidence for a prognostic role of the presence of CD3 + , CD4 + , CD8 + , FoxP3 + , and PD1 + TILs in the tumor epithelium of advanced stage, HPV-negative HNSCC patients treated with primary chemoradiotherapy. SN - 1432-0851 UR - https://www.unboundmedicine.com/medline/citation/31980916/Digital_pathology_aided_assessment_of_tumor_infiltrating_T_lymphocytes_in_advanced_stage_HPV_negative_head_and_neck_tumors_ L2 - https://dx.doi.org/10.1007/s00262-020-02481-3 DB - PRIME DP - Unbound Medicine ER -