TCR Repertoire Diversity of Peripheral PD-1⁺CD8⁺ T Cells Predicts Clinical Outcomes after Immunotherapy in Patients with Non–Small Cell Lung Cancer

Correlations of TCR diversity with the response and PFS associated with PD-1 or PD-L1 inhibitors. A, Comparison of PD-1⁺ CD8⁺ TCR diversity between the DC and PD subgroups after PD-1/PD-L1 inhibitor treatment in the discovery set (n = 25). B, An ROC curve was used to distinguish PD cases from DC cases in the discovery set (n = 25). C, PFS stratified by PD-1⁺ CD8⁺ TCR diversity in the discovery set (n = 25). D, PFS stratified by PD-1⁺ CD8⁺ TCR diversity in the validation set (n = 15). E, OS stratified by PD-1⁺ CD8⁺ TCR diversity in the discovery set (n = 25). F, OS stratified by PD-1⁺ CD8⁺ TCR diversity in the validation set (n = 15). G, Sensitivity and specificity of TCR diversity for determining the clinical response (DC vs. PD) to PD-1 or PD-L1 inhibitors (n = 40; DC, n = 23, and PD, n = 17).

Cox regression model assessing the correlation of clinical variables with PFS (A) and OS (B). LUAD, lung adenocarcinoma; LUSC,lung squamous cell carcinoma.

A, Comparison of TCR diversity in PBMCs between the DC and PD subgroups after PD-1/PD-L1 inhibitor treatment (n = 18). B, PFS stratified by TCR diversity in PBMCs (n = 18).

Correlations of the dynamic changes in TCR clonality with the response and PFS associated with PD-1 or PD-L1 inhibitors (n = 19). A, Waterfall plot of the best observed response to PD-1/PD-L1 inhibitors and the corresponding change in PD-1⁺ CD8⁺ TCR clonality. B, Dynamic changes in PD-1⁺ CD8⁺ TCR clonality and the corresponding changes in the MVAF in cfDNA. MVAF indicates the maximum variant allele frequency based on the response to PD-1/PD-L1 inhibitors. C, The response to immunotherapy based on changes in TCR clonality. D, PFS stratified by dynamic changes in PD-1⁺ CD8⁺ TCR clonality (increased vs. decreased). PsPD, pseudo PD. E, OS stratified by dynamic changes in PD-1⁺ CD8⁺ TCR clonality (increased vs. decreased).