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.

Retinoblastoma Is characterized by a cold, CD8+ cell poor, PD-L1- microenvironment, which turns into hot, CD8+ cell rich, PD-L1+ after chemotherapy / Miracco, Clelia; Toti, Paolo; Gelmi, Maria Chiara; Aversa, Sara; Baldino, Gennaro; Galluzzi, Paolo; De Francesco, Sonia; Petrelli, Federica; Sorrentino, Ester; Belmonte, Giuseppe; Galimberti, Daniela; Bracco, Sandra; Hadjistilianou, Theodora. - In: INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE. - ISSN 1552-5783. - 62:2(2021), pp. 1-14. [10.1167/iovs.62.2.6]

Retinoblastoma Is characterized by a cold, CD8+ cell poor, PD-L1- microenvironment, which turns into hot, CD8+ cell rich, PD-L1+ after chemotherapy

Aversa, Sara;
2021

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.
File allegati a questo prodotto
File Dimensione Formato  
Miracco_Retinoblastoma_2021.pdf

accesso aperto

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 4.51 MB
Formato Adobe PDF
4.51 MB Adobe PDF Visualizza/Apri PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11573/1491231
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 5
  • ???jsp.display-item.citation.isi??? 5
social impact