IMMUNE SCENARIO IDENTIFICATION COMBINING MULTIPLEXED, QUANTITATIVE, AND ADVANCED IMAGING ANALYSIS COULD BE RELEVANT IN IMMUNOTHERAPY AGAINST GLIOBLASTOMA AND GRADE 4 ASTROCYTOMA.

in Pathobiology : journal of immunopathology, molecular and cellular biology by Miguel A Idoate, Mikel Ariz-Galilea, Ainhoa Urbiola-Casales, Miriam Alonso-García, Jesús Machuca-Aguado, Carlos Ortiz de Solórzano, Eloy Rivas-Infante, Rainiero Avila-Polo, Michele Biscuola

TLDR

  • The study used multiplex technology and advanced imaging analysis to identify four distinct immune scenarios in glioblastoma, including a favorable scenario characterized by a high EC/IC ratio, which may hold potential for selecting immunotherapy candidates.
  • The study highlights the importance of identifying and targeting unfavorable immune scenarios, particularly in the context of incomplete surgical resection, to improve patient outcomes.

Abstract

Introduction In our research on understanding glioblastoma's resistance mechanisms to immunotherapy, we extensively investigated through an innovative technology that enables the simultaneous assessment of multiple biomarkers. With this approach, we aim to gain deeper insights into the interplay between immunosuppressive cells (IC) and effector cells (EC). Methods It were studied 126 cases of glioblastoma employing tissue microarrays stained with a panel of immune infiltrate validated via multiplex immunofluorescence and quantified by advanced image analysis. All cases were categorized according to an EC/IC ratio and their respective medians. Statistical correlations between cell populations and with survival were calculated. Results M2 macrophages were the most abundant IC, followed by a variable number of EC and pro-tumoral activated microglia, and a scant quantity of FoxP3 cells. EC showed a statistically significant direct positive correlation with IC. The patients with tumors exhibiting an EC/IC ratio ≤0.063 displayed a significantly poorer outcome. Furthermore, in the context of incomplete surgical resection, significant differences were evident considering immune scenarios. Conclusions By integrating multiplex technology with advanced imaging analysis, we successfully identified 4 distinct immune scenarios in glioblastoma. We observed a favorable immune scenario characterized by a relatively high EC/IC ratio, which is especially evident in the clinical setting of incomplete tumor resection. This promising immune scenario holds significant potential for selecting suitable candidates for immunotherapy in glioblastoma.

Overview

  • The study aimed to understand glioblastoma's resistance mechanisms to immunotherapy by investigating the interplay between immunosuppressive cells (IC) and effector cells (EC).
  • A novel technology was used to assess multiple biomarkers simultaneously, exploring 126 cases of glioblastoma through tissue microarrays stained with a validated panel of immune infiltrate.
  • The study aimed to identify distinct immune scenarios in glioblastoma and determine their potential impact on patient outcome, particularly in the context of incomplete surgical resection.

Comparative Analysis & Findings

  • M2 macrophages were the most abundant immunosuppressive cell type, followed by a variable number of effector cells (EC) and pro-tumoral activated microglia, and a scarce quantity of FoxP3 cells.
  • Effector cells showed a statistically significant direct positive correlation with immunosuppressive cells.
  • Patients with tumors exhibiting an EC/IC ratio ≤0.063 displayed a significantly poorer outcome, highlighting the importance of identifying and targeting this unfavourable immune scenario.

Implications and Future Directions

  • The study's findings have significant implications for selecting suitable candidates for immunotherapy in glioblastoma, particularly in the context of incomplete surgical resection.
  • Further research is needed to explore the potential of integrating multiplex technology with advanced imaging analysis to identify distinct immune scenarios in glioblastoma.
  • Future studies should aim to validate the clinical relevance of the identified immune scenarios and investigate potential therapeutic strategies to enhance the immune response.
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