Heterogeneous distribution pattern of CD3+ tumor-infiltrated lymphocytes (TILs) and high combined positive score (CPS) favored the prognosis of resected early stage small-cell lung cancer

Abstract

Purpose: This study aimed to illustrate the heterogeneity of immune features in small cell lung cancer (SCLC). Methods: Immunohistochemistry (IHC) staining of CD3, CD4, CD8 and PD-L1 were performed with 55 SCLC FFPE samples from radical resections. Quantitative assessment of CD3+ tumor-infiltrated lymphocytes (TILs) to present the heterogeneity in the tumor and the stroma areas. Hotspots of TILs were evaluated to illustrate the potential relationship between TIL-density and its immune competence. Programmed death ligand-1 (PD-L1) expressed on both tumor TILs (t-TILs) and stroma TILs (s-TILs) was evaluated and quantitatively described as values of tumor positive score (TPS) and combined positive score (CPS). The clinical value of TPS and CPS were further identified according to their relationship with disease-free survival (DFS). Results: More abundant CD3+ TILs were observed in the tumor stroma than that within the parenchyma (15.02±2.25% vs. 1.58±0.35%) . The amount of CD3+ s-TILs were positively correlated with DFS. The CD3+/CD4+ subset of the TILs was found more favorable to DFS compared to the CD3+/CD8+ subset. Hotspots of CD3+ TILs were observed in tumor regions and patients with more Hotspots of CD3+ TILs have better outcomes. CPS were more reliable than TPS to describe PD-L1 expression in SCLC and it was found positively correlated with tumor size and DFS. Conclusions: The immune microenvironment of SCLC was heterogeneous. Hotspots, the amount of CD3/CD4+ TILs and the CPS value were found valuable in determine the anti-tumor immunity and predicting the clinical outcome of SCLC patients.

Keywords

• Small-cell lung cancer
• Heterogeneity
• Tumor-infiltrated lymphocytes
• Tumor positive score
• Combined positive score
• Survival