Spatial heterogeneity of infiltrating immune cells in the tumor microenvironment of non-small cell lung cancer
Xinyue Liu, Yan Kong, You‐Wen Qian, Haoyue Guo, Lishu Zhao, Hao Wang, Kandi Xu, Li Ye, Yujin Liu, Hui Lu, Yayi He
Abstract
• Immune cells showed heterogeneous distribution in TME of NSCLC. • Efficientnet-B3-based model realized tumor and immune region segmentation. • TIME could be classified into three groups according to CD8+ T-cell density. • Single chromogenic IHC slices overlapping could realize mIHC simulation. Tumor-infiltrating lymphocytes (TILs) are essential components of the tumor microenvironment (TME) of non-small cell lung cancer (NSCLC). Still, it is difficult to describe due to their heterogeneity. In this study, five cell markers from NSCLC patients were analyzed. We segmented tumor cells (TCs) and TILs using Efficientnet-B3 and explored their quantitative information and spatial distribution. After that, we simulated multiplex immunohistochemistry (mIHC) by overlapping continuous single chromogenic IHCs slices. As a result, the proportion and the density of programmed cell death-ligand 1 (PD-L1)-positive TCs were the highest in the core. CD8+ T cells were the closest to the tumor (median distance: 41.71 μm), while PD-1+T cells were the most distant (median distance: 62.2μm), and our study found that most lymphocytes clustered together within the peritumoral range of 10-30 μm where cross-talk with TCs could be achieved. We also found that the classification of TME could be achieved using CD8+ T-cell density, which is correlated with the prognosis of patients. In addition, we achieved single chromogenic IHC slices overlap based on CD4-stained IHC slices. We explored the number and spatial distribution of cells in heterogeneous TME of NSCLC patients and achieved TME classification. We also found a way to show the co-expression of multiple molecules economically.