Retinoblastoma Is Characterized by a Cold, CD8+ Cell Poor, PD-L1- Microenvironment, Which Turns Into Hot, CD8+ Cell Rich, PD-L1+ After Chemotherapy

Invest Ophthalmol Vis Sci. 2021 Feb 1;62(2):6. doi: 10.1167/iovs.62.2.6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7-H1 Antigen / immunology
  • B7-H1 Antigen / metabolism*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Infant
  • Infant, Newborn
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Programmed Cell Death 1 Receptor / immunology
  • Programmed Cell Death 1 Receptor / metabolism*
  • Retinal Neoplasms / immunology
  • Retinal Neoplasms / metabolism*
  • Retinal Neoplasms / pathology
  • Retinoblastoma / immunology
  • Retinoblastoma / metabolism*
  • Retinoblastoma / pathology
  • Retrospective Studies
  • Time Factors
  • Tumor Microenvironment / immunology*

Substances

  • B7-H1 Antigen
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor