Predictive impact of systemic inflammation and tertiary lymphoid structures on pathological complete response in neoadjuvant-treated advanced esophageal squamous carcinoma patients.

[BACKGROUND] It is important to assess systemic and local immune responses to determine the effects of antitumor treatment. Moreover, identifying factors related to pathological complete response (pCR) is important for optimizing treatment decisions.

[METHODS] In this study, we retrospectively enrolled 364 esophageal squamous carcinoma patients who underwent radical resection of esophageal cancer after preoperative intervention. Among them, 62 reached pCR, whereas 302 did not (non-pCR). The clinicopathological features of the patients were assessed to identify the predictors of pCR using a logistic regression model. Tertiary lymphoid structure (TLS) features were analyzed via H&E staining, multiplex immunofluorescence, and immunohistochemistry to analyze the local immune response.

[RESULTS] The results of multivariate regression revealed that low systemic inflammatory status was significantly related to pCR, which was verified by a low systemic immune-inflammation index (SII) combined with the neutrophil-to-lymphocyte ratio (NLR) (SII+NLR) (odds ratio: 3.413, 95% CI: 1.819-7.165; P = 0.017). Specifically, a high TLS density but low PD-1 + and CD8 + cell fractions inside TLS in the tumor bed were closely related to pCR.

[CONCLUSION] Systemic/local immune profiles are related to pCR. A decreased SII+NLR independently predicts pCR, whereas different TLS features may be associated with pCR. Immune responses should be given attention to optimize treatment for advanced esophageal squamous carcinoma patients receiving preoperative treatment.