Comparative profiling of T cell and macrophage subsets in cutaneous squamous cell carcinoma and basal cell carcinoma

The yearly incidence of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) continues to rise in the ongoing skin cancer epidemic. Mousa and colleagues have previously highlighted the crucial role of the immune system in the development and progression of both tumor types. Therefore, immune cells in close proximity to, or even infiltrating, the tumor should be of particular interest. Previously, we demonstrated differential expression of immune checkpoint markers, including both activating and inhibitory markers, between BCC and cSCC. The present study aims to further investigate the tumor microenvironment, with a focus on T cells, macrophages, and dendritic cells, among others. Furthermore, we analyzed possible associations between cSCC marker expression and clinicopathological data. In order to evaluate the expression levels and topographic distribution profiles of CD4, CD8, Foxp3, CD68, CD163, and CD11c, tissue microarrays of the invasive front as well as the tumor core of BCC and cSCC samples were analyzed. Chromogenic immunohistochemistry was performed, and the labeling index was determined using QuPath. Stroma cell labeling indices of CD4**, CD8*, Foxp3*, CD68*, CD163**, and CD11c* were significantly higher in both the tumor core and the invasive front of cSCC samples as compared to BCC (*p < 0.001; **p < 0.050). In cSCC, the ratios of CD163/CD68 (p < 0.001) and CD163/CD11c (p = 0.001) were markedly elevated. The invasive front of both tumor entities showed higher expression levels of all immune markers compared to the tumor core, when significant levels were reached. Lastly, an association between cSCC sLI CD4 and T status (p = 0.011), CD11c and N status (p = 0.041), CD68 and infiltrations depth (p = 0.018), as well as CD8 and CD11c and previous tumor (p = 0.006; p = 0.029, respectively) was observed. This study provides a comprehensive analysis of the tumor microenvironment (TME) of BCC and cSCC, emphasizing the distinct expression patterns of the TME with regard to T cell and macrophage-associated markers. The cSCC TME exhibited higher expression levels of all investigated markers, predominantly at the invasive front rather than the tumor core. Further, more comprehensive analysis of these TMEs is required to understand their impact on clinicopathological data, response to immunotherapy and predictive ability.