Immune cellular patterns of distribution affect outcomes of patients with non-small cell lung cancer

Background Study of the geographic distribution of cellular populations and their interaction with malignant cells in non-small cell lung cancer (NSCLC) is essential to understand the roles of cellular populations and potentially design new therapeutic approaches. Material and Methods We studied 225 formalin-fixed, paraffin-embedded tumor tissue samples from patients with stage I-III NSCLC—142 adenocarcinomas and 83 squamous cell carcinomas—placed in tissue microarrays. Twenty-three markers were used, including T-cell, B-cell, immune checkpoint, and myeloid cell markers, placed in five multiplex immunofluorescence panels. We used dimensional data reduction and cellular spatial distribution to identify cell phenotypes and their cellular distribution across panels. In addition, we analyzed associations between cellular spatial distribution patterns and clinicopathologic variables, tumor mutational status, and outcomes. Results Overall, we observed two patterns of cellular distribution—unmixed and mixed—related to T-cells, B-cells, granulocytic cells, and macrophages, and we detected various cellular interactions between malignant and immunosuppressive cells and various associations between cell distribution and clinicopathologic characteristics. Cellular distribution patterns and the distance from various cell phenotypes to malignant cells were associated with recurrence-free survival and overall survival in univariate and multivariable analysis. Conclusions Diverse populations of tumor cells and tumor-associated immune cell phenotypes can be present in NSCLC samples. Spatial distribution is a new tool to better understand the tumor microenvironment and help select therapeutic interventions.