Association of Circulating T Cell and Tumor Microenvironment Profiles with Immune Checkpoint Blockade Outcomes in...

Area of Science:

• Oncology
• Immunology
• Biomarker Discovery

Background:

• Immune checkpoint blockade (ICB) efficacy in sarcoma is limited to a subset of patients.
• Predictive biomarkers are crucial for optimizing patient selection for ICB therapy.

Purpose of the Study:

• To identify biomarkers associated with response and resistance to ICB in sarcoma patients.
• To explore circulating T cell immunotypes and tumor microenvironment (TME) subtypes as predictors of ICB outcomes.

Main Methods:

• Analyzed peripheral blood mononuclear cells (PBMCs) and tumor tissues from sarcoma patients on ICB clinical trials.
• Utilized flow cytometry to define T cell immunotypes and RNA sequencing to classify TME subtypes.
• Applied a deep-learning model to hematoxylin and eosin (H&E) slides for lymphoid aggregate quantification.

Main Results:

• A proliferative (PRO) circulating T cell immunotype correlated with inferior overall survival (OS).
• An immune-enriched/non-fibrotic TME subtype was linked to higher response rates, improved progression-free survival, and longer OS.
• Automated H&E slide analysis showed potential in identifying immune-enriched TME features.

Conclusions:

• PRO T cell immunotype predicts poor ICB outcomes, whereas immune-enriched/non-fibrotic TME predicts favorable outcomes in sarcoma.
• Multimodal biomarker approaches, including T cell immunotypes and TME characteristics, are essential for predicting ICB response.
• Automated analysis of H&E slides offers a promising tool for TME assessment in immunotherapy selection.