1096 - Peripheral PD-1?CD8? T-cell TCR Dynamics during Radiotherapy Predict Survival in Unresectable Locally Advanced Non-Small Cell Lung Cancer
Presenter(s)
Y. Jiang, Y. Yang, L. Wu, and N. Bi; Department 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
Purpose/Objective(s):
To determine whether T-cell receptor (TCR) repertoire diversity and longitudinal dynamics of circulating PD-1?CD8? T cells are associated with progression-free survival (PFS) in unresectable locally advanced non-small cell lung cancer (LA-NSCLC) treated with chemoradiotherapy.
Materials/Methods:
We prospectively enrolled 63 patients with unresectable LA-NSCLC undergoing chemoradiotherapy. Peripheral blood PD-1?CD8? T cells were isolated from peripheral blood mononuclear cells at three time points: pre-radiotherapy (pre-RT), during radiotherapy (on-RT; ~20th fraction), and post-radiotherapy (post-RT), yielding 141 samples. TCR sequencing quantified repertoire diversity (D50) and clonality. Associations between TCR metrics (and their interval changes) and PFS were analyzed.
Results:
A higher D50 index on-RT was significantly associated with improved median PFS (not reached vs. 21.95 months; p = 0.0246), regardless of the timing of immunotherapy. Patients with more stable TCR diversity and clonality on-RT experienced significantly longer PFS. Specifically, patients with low D50 index variation between on-RT and post-RT had a median PFS that was not reached (95% confidence interval [CI]: 30.72–NA), compared with 21.95 months (95% CI: 17.84–NA; p = 0.018) in the high-variation group. Similarly, patients with low clonality variation demonstrated longer PFS from pre-RT to on-RT (30.72 vs. 21.95 months; p = 0.0425) and from on-RT to post-RT (not reached vs. 22.21 months; p = 0.0331). Clonal tracking analyses revealed that patients with short-PFS exhibited a higher proportion of markedly decreased TCR clones, particularly among high-frequency clones, suggesting impaired antitumor immune responses.Conclusion:
Peripheral PD-1?CD8? TCR diversity and its dynamic changes on-RT are associated with PFS in patients with LA-NSCLC. These findings suggest that TCR repertoire profiling of circulating PD-1?CD8? T cells may serve as a non-invasive biomarker to identify patients less likely to benefit from consolidation immunotherapy. Further validation in larger, prospective cohorts is warranted.