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ABSTRACT: Purpose
To investigate the impact of chemotherapy (CHT) on human retinoblastoma (RB) tumor microenvironment (TME).Cases and methods
Ninety-four RBs were studied, including 44 primary RBs treated by upfront surgery (Group 1) and 50 primary RBs enucleated after CHT (CHT), either intra-arterial (IAC; Group 2, 33 cases) or systemic (S-CHT; Group 3, 17 cases). Conventional and multiplexed immunohistochemistry were performed to make quantitative comparisons among the three groups, for the following parameters: tumor-infiltrating inflammatory cells (TI-ICs); programmed cell death protein 1 (PD-1) positive TI-ICs; Ki67 proliferation index; gliosis; PD-1 ligand (PD-L1) protein expression; vessel number. We also correlated these TME factors with the presence of histological high-risk factors (HHRF+) and RB anaplasia grade (AG).Results
After CHT, a decrease in both RB burden and Ki67 positivity was observed. In parallel, most subsets of TI-ICs, PD-1+ TI-ICs, gliosis, and PD-L1 protein expression significantly increased (P < 0.001, P = 0.02, P < 0.001, respectively). Vessel number did not significantly vary. Age, HHRFs+ and AG were significantly different between primary and chemoreduced RBs (P < 0.001, P = 0.006, P = 0.001, respectively) and were correlated with most TME factors.Conclusions
CHT modulates host antitumor immunity by reorienting the RB TME from anergic into an active, CD8+, PD-L1+ hot state. Furthermore, some clinicopathological characteristics of RB correlate with several factors of TME. Our study adds data in favor of the possibility of a new therapeutic scenario in human RB.
SUBMITTER: Miracco C
PROVIDER: S-EPMC7862737 | biostudies-literature | 2021 Feb
REPOSITORIES: biostudies-literature
Miracco Clelia C Toti Paolo P Gelmi Maria Chiara MC Aversa Sara S Baldino Gennaro G Galluzzi Paolo P De Francesco Sonia S Petrelli Federica F Sorrentino Ester E Belmonte Giuseppe G Galimberti Daniela D Bracco Sandra S Hadjistilianou Theodora T
Investigative ophthalmology & visual science 20210201 2
<h4>Purpose</h4>To investigate the impact of chemotherapy (CHT) on human retinoblastoma (RB) tumor microenvironment (TME).<h4>Cases and methods</h4>Ninety-four RBs were studied, including 44 primary RBs treated by upfront surgery (Group 1) and 50 primary RBs enucleated after CHT (CHT), either intra-arterial (IAC; Group 2, 33 cases) or systemic (S-CHT; Group 3, 17 cases). Conventional and multiplexed immunohistochemistry were performed to make quantitative comparisons among the three groups, for ...[more]