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Updated: May 18, 2026
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Published on: August 14, 2019
Peripheral PD-1⁺CD8⁺ T-cell TCR Dynamics During Radiation Therapy Predict Survival in Unresectable Locally Advanced
Ying Jiang1, Yin Yang1, Linfang Wu2
1Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
T-cell receptor (TCR) diversity in PD-1⁺CD8⁺ T cells during radiation therapy correlates with progression-free survival (PFS) in locally advanced non-small cell lung cancer (LA-NSCLC). Stable TCR profiles predict better outcomes, suggesting a potential noninvasive biomarker for immunotherapy response.
Area of Science:
- Immunology
- Oncology
- Genomics
Background:
- Immune checkpoint inhibitors (ICIs) enhance outcomes in unresectable locally advanced non-small cell lung cancer (LA-NSCLC).
- Predictive biomarkers for immunotherapy response in LA-NSCLC are limited.
- PD-1⁺CD8⁺ T cells are a key activated subset responsive to PD-1 blockade.
Purpose of the Study:
- To investigate the potential of T-cell receptor (TCR) repertoire profiling in circulating PD-1⁺CD8⁺ T cells as a noninvasive biomarker.
- To correlate dynamic changes in TCR diversity metrics with progression-free survival (PFS) in LA-NSCLC patients undergoing chemoradiation therapy.
Main Methods:
- Prospective enrollment of 63 LA-NSCLC patients treated with chemoradiation.
- Isolation of peripheral blood PD-1⁺CD8⁺ T cells at pre-radiation, during radiation (on-RT), and post-radiation (post-RT) time points.
- TCR sequencing to assess repertoire diversity and dynamic changes, correlated with PFS.
Main Results:
- Higher D50 index on-RT was linked to improved median PFS (not reached vs. 21.95 months).
- Stable TCR diversity and clonality during treatment correlated with significantly longer PFS.
- Low variation in D50 index and clonality between on-RT and post-RT predicted superior PFS outcomes.
Conclusions:
- Peripheral PD-1⁺CD8⁺ TCR diversity and its dynamics during radiation therapy are associated with PFS in LA-NSCLC.
- TCR repertoire profiling of circulating PD-1⁺CD8⁺ T cells shows promise as a noninvasive biomarker.
- Further validation in larger cohorts is necessary to confirm utility in predicting immunotherapy response.
