Identification of an excellent prognosis subset of human papillomavirus-associated oropharyngeal cancer patients by quantification of intratumoral CD103+ immune cell abundance.
Adult
Aged
Aged, 80 and over
Antigens, CD
/ immunology
Biomarkers, Tumor
/ analysis
Carcinoma, Squamous Cell
/ immunology
Combined Modality Therapy
Female
Follow-Up Studies
Humans
Immunologic Memory
/ immunology
Integrin alpha Chains
/ immunology
Male
Middle Aged
Oropharyngeal Neoplasms
/ immunology
Papillomaviridae
/ isolation & purification
Papillomavirus Infections
/ complications
Prognosis
Prospective Studies
Retrospective Studies
Survival Rate
Young Adult
CD103
human papillomavirus
oropharyngeal cancer
prognosis
survival
tissue-resident memory cells
Journal
Annals of oncology : official journal of the European Society for Medical Oncology
ISSN: 1569-8041
Titre abrégé: Ann Oncol
Pays: England
ID NLM: 9007735
Informations de publication
Date de publication:
01 10 2019
01 10 2019
Historique:
pubmed:
11
8
2019
medline:
1
8
2020
entrez:
11
8
2019
Statut:
ppublish
Résumé
Accurate prognostic stratification of human papillomavirus-associated oropharyngeal cancers (HPV+OPSCC) is required to identify patients potentially suitable for treatment deintensification. We evaluated the prognostic significance of CD103, a surface marker associated with tissue-resident memory T cells (TRMs), in two independent cohorts of patients with HPV+OPSCC. The abundance and distribution of CD103+ immune cells were quantified using immunohistochemistry in a cohort of 189 HPV+OPSCC patients treated with curative intent and correlated with outcome. Findings were then validated in an independent cohort comprising 177 HPV+OPSCCs using univariable and multivariable analysis. Intratumoral CD103+ immune cells were characterized by multispectral fluorescence immunohistochemistry and gene expression analysis. High intratumoral abundance of CD103+ immune cells using a ≥30% cut-off was found in 19.8% of tumors in the training cohort of HPV+OPSCC patients and associated with excellent prognosis for overall survival (OS) with adjusted hazard ratio (HR) of 0.13 [95% confidence interval (CI) 0.02-0.94, P = 0.004]. In the independent cohort of HPV+OPSCCs, 20.4% had high intratumoral CD103+ abundance and an adjusted HR for OS of 0.16 (95% CI 0.02-1.22, P = 0.02). Five year OS of patients with high intratumoral CD103 was 100% across both cohorts. The C-statistic for the multivariate prognostic model with stage and age was significantly improved in both cohorts with the addition of intratumoral CD103+ cell abundance. On the basis of spatial location, co-expression of CD8 and CD69, and gene expression profiles, intratumoral CD103+ cells were consistent with TRMs. Quantification of intratumoral CD103+ immune cell abundance provides prognostic information beyond that provided by clinical parameters such as TNM-staging, identifying a population of low risk HPV+OPSCC patients who are good candidates for trials of deintensification strategies.
Sections du résumé
BACKGROUND
Accurate prognostic stratification of human papillomavirus-associated oropharyngeal cancers (HPV+OPSCC) is required to identify patients potentially suitable for treatment deintensification. We evaluated the prognostic significance of CD103, a surface marker associated with tissue-resident memory T cells (TRMs), in two independent cohorts of patients with HPV+OPSCC.
PATIENTS AND METHODS
The abundance and distribution of CD103+ immune cells were quantified using immunohistochemistry in a cohort of 189 HPV+OPSCC patients treated with curative intent and correlated with outcome. Findings were then validated in an independent cohort comprising 177 HPV+OPSCCs using univariable and multivariable analysis. Intratumoral CD103+ immune cells were characterized by multispectral fluorescence immunohistochemistry and gene expression analysis.
RESULTS
High intratumoral abundance of CD103+ immune cells using a ≥30% cut-off was found in 19.8% of tumors in the training cohort of HPV+OPSCC patients and associated with excellent prognosis for overall survival (OS) with adjusted hazard ratio (HR) of 0.13 [95% confidence interval (CI) 0.02-0.94, P = 0.004]. In the independent cohort of HPV+OPSCCs, 20.4% had high intratumoral CD103+ abundance and an adjusted HR for OS of 0.16 (95% CI 0.02-1.22, P = 0.02). Five year OS of patients with high intratumoral CD103 was 100% across both cohorts. The C-statistic for the multivariate prognostic model with stage and age was significantly improved in both cohorts with the addition of intratumoral CD103+ cell abundance. On the basis of spatial location, co-expression of CD8 and CD69, and gene expression profiles, intratumoral CD103+ cells were consistent with TRMs.
CONCLUSION
Quantification of intratumoral CD103+ immune cell abundance provides prognostic information beyond that provided by clinical parameters such as TNM-staging, identifying a population of low risk HPV+OPSCC patients who are good candidates for trials of deintensification strategies.
Identifiants
pubmed: 31400196
pii: S0923-7534(19)60980-4
doi: 10.1093/annonc/mdz271
pii:
doi:
Substances chimiques
Antigens, CD
0
Biomarkers, Tumor
0
Integrin alpha Chains
0
alpha E integrins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1638-1646Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.