Prognostic Impact of the Immune-Cell Infiltrate in N1-Positive Non–Small-Cell Lung Cancer

The analysis of peritumoral immune cells may help to identify patients that profit from further immunotherapy treatment after lung cancer surgery. We analyzed tumors from 174 patients and identified high levels of tumor infiltrating lymphocytes and M1-like tumor-associated macrophages as positive predictive factor whereas the abundance of regulatory T-cells was associated with poorer outcome in distinct histologic NSCLC subtypes. Introduction The tumoral immune milieu plays a crucial role for the development of non-small cell lung cancer (NSCLC) and may influence individual prognosis. We analyzed the predictive role of immune cell infiltrates after curative lung cancer surgery. Materials and Methods The tumoral immune-cell infiltrate from 174 patients with pN1 NSCLC and adjuvant chemotherapy was characterized using immunofluorescence staining. The density and distribution of specific immune cells in tumor center (TU), invasive front (IF) and normal tissue (NORM) were correlated with clinical parameters and survival data. Results Tumor specific survival (TSS) of all patients was 69.9% at 5 years. The density of tumor infiltrating lymphocytes (TIL) was higher in TU and IF than in NORM. High TIL density in TU (low vs. high: 62.0% vs. 86.7%; p=0.011) and the presence of cytotoxic T-Lymphocytes (CTLs) in TU and IF were associated with improved TSS (positive vs. negative: 90.6% vs. 64.7% p=0.024). High TIL-density correlated with PD-L1 expression levels ≥50% (p<0.001). Multivariate analysis identified accumulation of TIL (p=0.016) and low Treg density (p=0.003) in TU as negative prognostic predictors in squamous cell carcinoma (p=0.025), whereas M1-like tumor- associated macrophages (p=0.019) and high PD-L1 status (p=0.038) were associated with better survival in adenocarcinoma. Conclusion The assessment of specific intratumoral immune cells may serve as a prognostic predictor in pN1 NSCLC. However differences were observed related to adenocarcinoma or squamous cell carcinoma histology. Prospective assessment of the immune-cell infiltrate and further clarification of its prognostic relevance could assist patient selection for upcoming perioperative immunotherapies. The analysis of peritumoral immune cells may help to identify patients that profit from further immunotherapy treatment after lung cancer surgery. We analyzed tumors from 174 patients and identified high levels of tumor infiltrating lymphocytes and M1-like tumor-associated macrophages as positive predictive factor whereas the abundance of regulatory T-cells was associated with poorer outcome in distinct histologic NSCLC subtypes.