Predictive value of FDG PET/CT parameters and T cell subsets in stage II/III non-small cell lung cancer with neoadjuvant immunotherapy

초록

Background This study aims to assess the utility of FDG PET/CTderived parameters as predictive imaging biomarkers in the neoadjuvant setting and their association with specific T cell subsets. Methods Patients with clinical stage II/III NSCLC who underwent immunotherapy-based neoadjuvant therapy and had both pre- and post-treatment FDG PET/CT scans were retrospectively included. Biopsy specimens obtained prior to treatment were analyzed to quantify T cell subsets. The maximum standardized uptake value (maxSUV) and tumor to liver ratio (TLR) were measured in total tumors of each patient. Immune cell populations were quantified digitally as percentages. Results Eleven pairs of PET images and 8 corresponding biopsy specimens were analyzed. Among the cases, the ratio of patients achieving pathological complete response (pCR) versus no-pCR was 6:5 and 4:4, respectively. Pre-treatment maxSUV and TLR were not significantly different between pCR vs. no-pCR groups. However, post-treatment maxSUV and TLR tended to be lower or were significantly lower in the pCR group (median, 2.570 vs. 4.720, p = 0.052 and 1.505 vs. 2.140, p < 0.01, respectively). Additionally, changes in maxSUV (△maxSUV) and TLR (△TLR) were significantly higher in the pCR group (0.83 vs. 0.49, p < 0.01, and 0.82 vs. 0.58, p < 0.01, respectively). Granzyme B (+) CD8 cells of CD8 cells were significantly elevated in the pCR group compared to no-pCR (49.575 vs. 21.11, p < 0.05) and TIGIT (+) CD8 cells of CD8 cells also showed a trend toward higher levels (25.26 vs. 5.805, p = 0.057). Pre-treatment TLR showed a positive correlation with Ki67(+) CD8 cells of total cells (r = 0.714, p < 0.05). △TLR showed a positive correlation with TIGIT (+) CD8 cells of CD8 cells (r = 0.786, p < 0.05) and TIGIT (+) CD8, CD3, CD4 cells of total cells (all, r = 0.714, p < 0.05). Conclusions The TLR and maxSUV parameters from FDG PET/CT hold potential as non-invasive imaging biomarkers for predicting responses to neoadjuvant immunotherapy in NSCLC. These parameters are significantly associated with markers of T cell activation and exhaustion, underscoring their relevance in understanding the tumor immune microenvironment.