CLEAR-IT, a framework for contrastive learning to capture the immune composition of tumor microenvironments

Daniel Spengler1, Serafim Korovin1, Kirti Prakash1,2

  • 1Delft Center for Systems and Control, Delft University of Technology, Delft, the Netherlands.

Communications Biology
|April 16, 2026
PubMed

Insights

CLEAR-IT, a novel self-supervised framework, enables accurate cell phenotyping in the tumor microenvironment using minimal labels. This approach enhances cancer research scalability and prognostic modeling.

Area of Science:

  • Computational pathology
  • Cancer biology
  • Machine learning for medical imaging

Background:

  • Accurate cell phenotyping in the tumor microenvironment is crucial for cancer research.
  • Current methods often require precise cell segmentation, limiting scalability.

Purpose of the Study:

  • Introduce Contrastive Learning Enabled Accurate Registration of Immune and Tumor cells (CLEAR-IT), a self-supervised framework for cell-level feature learning.
  • Develop a label-efficient and segmentation-light approach for scalable cell phenotyping.

Main Methods:

  • CLEAR-IT utilizes self-supervised learning on multiplexed images, focusing on cell locations to learn features.
  • The framework employs contrastive learning for robust feature extraction.
  • Evaluated performance using linear evaluation, hyperparameter optimization, and cross-modality testing.

Main Results:

  • CLEAR-IT encoders demonstrate strong performance, improving with optimization and maintaining accuracy with up to 90% fewer labels.
  • CLEAR-IT features enhance state-of-the-art classifiers, achieving comparable accuracy with less labeled data.
  • Prognostic modeling using CLEAR-IT identified survival-associated tissue features generalizing across cohorts and modalities.

Conclusions:

  • CLEAR-IT offers a scalable, label-efficient solution for cell phenotyping in digital pathology.
  • The framework significantly reduces reliance on extensive cell segmentation and labeling.
  • CLEAR-IT enhances existing workflows for tumor microenvironment analysis and prognostic prediction.

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