Interplay between glucocorticoids and tumor-infiltrating lymphocytes on the prognosis of adrenocortical carcinoma.
Adolescent
Adrenal Cortex Neoplasms
/ immunology
Adrenocortical Carcinoma
/ immunology
Adult
Aged
CD8-Positive T-Lymphocytes
/ drug effects
Female
Follow-Up Studies
Glucocorticoids
/ pharmacology
Humans
Immunotherapy
Lymphocytes, Tumor-Infiltrating
/ drug effects
Male
Middle Aged
Neoplasm Recurrence, Local
/ immunology
Prognosis
Retrospective Studies
Survival Rate
T-Lymphocytes, Cytotoxic
/ drug effects
T-Lymphocytes, Regulatory
/ drug effects
Young Adult
immunity
immunotherapy
lymphocytes, tumor-infiltrating
t-lymphocytes
tumor microenvironment
Journal
Journal for immunotherapy of cancer
ISSN: 2051-1426
Titre abrégé: J Immunother Cancer
Pays: England
ID NLM: 101620585
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
accepted:
01
04
2020
entrez:
1
6
2020
pubmed:
1
6
2020
medline:
18
3
2021
Statut:
ppublish
Résumé
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy. Tumor-related glucocorticoid excess is present in ~60% of patients and associated with particularly poor prognosis. Results of first clinical trials using immune checkpoint inhibitors were heterogeneous. Here we characterize tumor-infiltrating T lymphocytes (TILs) in ACC in association with glucocorticoids as potential explanation for resistance to immunotherapy. We performed immunofluorescence analysis to visualize tumor-infiltrating T cells (CD3 86.3% of ACC specimens showed tumor infiltrating T cells (7.7 cells/high power field (HPF)), including T helper (74.0%, 6.7 cells/HPF), cytotoxic T cells (84.3%, 5.7 cells/HPF) and Tregs (49.3%, 0.8 cells/HPF). The number of TILs was associated with better overall survival (HR for death: 0.47, 95% CI 0.25 to 0.87), which was true for CD4 Glucocorticoid excess is associated with T cell depletion and unfavorable prognosis. To reactivate the immune system in ACC by checkpoint inhibitors, an inhibition of adrenal steroidogenesis might be pivotal and should be tested in prospective studies.
Sections du résumé
BACKGROUND
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy. Tumor-related glucocorticoid excess is present in ~60% of patients and associated with particularly poor prognosis. Results of first clinical trials using immune checkpoint inhibitors were heterogeneous. Here we characterize tumor-infiltrating T lymphocytes (TILs) in ACC in association with glucocorticoids as potential explanation for resistance to immunotherapy.
METHODS
We performed immunofluorescence analysis to visualize tumor-infiltrating T cells (CD3
RESULTS
86.3% of ACC specimens showed tumor infiltrating T cells (7.7 cells/high power field (HPF)), including T helper (74.0%, 6.7 cells/HPF), cytotoxic T cells (84.3%, 5.7 cells/HPF) and Tregs (49.3%, 0.8 cells/HPF). The number of TILs was associated with better overall survival (HR for death: 0.47, 95% CI 0.25 to 0.87), which was true for CD4
CONCLUSION
Glucocorticoid excess is associated with T cell depletion and unfavorable prognosis. To reactivate the immune system in ACC by checkpoint inhibitors, an inhibition of adrenal steroidogenesis might be pivotal and should be tested in prospective studies.
Identifiants
pubmed: 32474412
pii: jitc-2019-000469
doi: 10.1136/jitc-2019-000469
pmc: PMC7264832
pii:
doi:
Substances chimiques
Glucocorticoids
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
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