T-cell Receptor Profiling of Blood to Detect Lung Cancer

Area of Science:

• Immunology
• Oncology
• Biomarker Discovery

Background:

• The blood T-cell receptor (TCR) repertoire contains valuable information about immune responses but is underutilized for cancer biomarker studies.
• Complexity and limited profiling data hinder the use of circulating T-cell repertoires in cancer diagnostics.

Purpose of the Study:

• To investigate the utility of blood TCR sequencing for early lung cancer detection.
• To develop and validate a novel biomarker score based on TCR repertoire analysis for lung cancer diagnosis.

Main Methods:

• Sequencing of peripheral blood leukocyte fraction from 633 individuals (case-control and screening cohorts).
• Development of the Tumor Immune Lymphocyte Score (TILS) using TCR specificity groups (TILS-A) or public TCR clonotypes (TILS-B).
• Validation of TILS classifiers in a lung cancer screening cohort and an external dataset.

Main Results:

• TILS-A, based on 125 TCR specificity groups, demonstrated superior lung cancer detection compared to TILS-B (49 public clonotypes).
• TILS classifiers provided predictive value, improving cancer prediction in individuals with indeterminate risk, even after adjusting for clinical factors.
• TILS-A showed association with both early- and late-stage lung cancer and improved accuracy when considering HLA status.

Conclusions:

• Circulating T-cell repertoire profiles hold significant value for lung cancer detection.
• The TILS score, particularly TILS-A, shows potential as a non-invasive diagnostic tool for lung cancer.
• Further validation supports the use of TCR sequencing-based biomarkers in clinical oncology.