Neoadjuvant chemo-immunotherapy increases tumor immune lymphocytes infiltration in resectable NSCLC.

Abstract

e20573 Background: NCIT (neoadjuvant Chemo-immunotherapy treatment) has revolutionized the treatment of resectable NSCLC due to its better MPR (major pathologic response) rate and pCR (pathologic complete response) rate over neoadjuvant chemotherapy or immunotherapy. However, the intrinsic mechanism underlying this treatment remains unclear. In recent years, the immune microenvironment has attracted considerable attention in the field of immunotherapy. In this study, we explored the relationship between tumor immune lymphocytes (TILs), tertiary lymphoid structures (TLS), and response to NCIT in resectable NSCLC and the change in TILs before and after NCIT. Methods: Twenty-five patients with stage IIA-IIIC NSCLC who underwent surgery after NCIT were enrolled in this retrospective study. Multiplex immunofluorescence (mIF) staining and image analysis assays were performed on the samples collected before and after NCIT for each patient. Results: Among the enrolled patients, 10 achieved MPR or pCR which were defined as response group, whereas 15 did not respond well to NCIT which were defined as non-response group. The results of the mIF assays revealed that NCIT was associated with an increase in immune lymphocytes, including CD3+ (tumor, p = 0.23; stroma, p < 0.01), CD4+ (tumor, p = 0.011; stroma, p < 0.001), CD4+Foxp3+ (tumor, p = 0.63; stroma, p < 0.001), CD8+ (tumor, p = 0.00031; stroma, p < 0.001), CD8+PD-1+ (tumor, p = 0.13; stroma, p = 0.022), PD-L1+CD68+ (tumor, p = 0.85; stroma, p = 0.041), and TLS (tertiary lymphoid structures, p = 0.00027). The comparison of TIL between response group and non-response group revealed that CD3, FOXP3+, and CD8+PD-1+ may serve as predictors of the response to neoadjuvant immunotherapy. Conclusions: To our knowledge, this is the first study to explore the relationship between TILs, TLS, and response to NCIT and TIL changes during NCIT in resectable Chinese NSCLC. In resectable NSCLC, the infiltration of immune cells before NCIT was correlated with the pathologic complete response, which enhanced the TILs as a promising predictor for selecting patients who were more likely to benefit from NCIT.