Spatial immune profiling characterizes tumor microenvironment heterogeneity between metastatic and non-metastatic cutaneous squamous cell carcinoma in organ transplant patients

Solid organ transplant recipients (sOTRs) face an increased risk of developing metastatic cutaneous squamous cell carcinoma (cSCC), largely due to chronic immunosuppression. While clinical risk factors are well established, the role of the tumor microenvironment (TME) in driving metastasis remains unclear. This study aimed to characterize the TME of metastatic (cSCC-M) versus non-metastatic (cSCC-nonM) primary lesions in sOTRs using Imaging Mass Cytometry (IMC). Tissue samples from five sOTRs, each with one cSCC-M and multiple cSCC-nonM lesions, were analyzed. IMC was used for high-dimensional spatial profiling, allowing quantitative assessment of cell composition and cellular interactions within the TME.cSCC-M samples showed increased infiltration of B cells and CD4+ T cells, while CD8+ T cells were more abundant in cSCC-nonM. Activation markers such as Granzyme B, Ki67, T-bet and PD-1 were highly expressed in both CD4+ and CD8+ T cells in cSCC-nonM, indicating a more active immune response. Notably, CD4+ T cells in cSCC-M interact with HLADR+ dendritic cells, an interaction absent in cSCC-nonM.These findings suggest cSCC-M is characterized by a distinct TME landscape, whereas cSCC-nonM exhibits a more activated immune profile. The observed differences may contribute to metastatic potential and highlight the importance of the immune landscape in disease progression.