Result interpretation - Human squamous cell carcinoma
The tumor microenvironment (TME) is a complex ecosystem involving various interactions between cancer cells and their microenvironment, ultimately contributing to tumor progression, metastasis and drug resistance. Understanding the cell interplay that occurs within the TME can facilitate the development of new therapeutic strategies.
Here, we used the scRNA-seq data derived from the diseased skin tissue of a patient with cutaneous squamous cell carcinoma (cSCC) (GSM4284326) and mapped the single cells to the ST section that ranked first in the section blast results.
The result page of this case study (Human squamous cell carcinoma) is available at b3ae1730-90b3-11ed-9695-b54d6690f34b . You can also access it from the home page.
To ensure a more comprehensive spatial mapping, we set the "redundancy" parameter to 10, given that the cell number is insufficient (2,366 cells). Additionally, we set the "KNN Number" to 0 to skip filtering cells in the latent space, as these two modalities were collected from the same dataset.
It has been reported that the tumor-specific keratinocyte (TSK) population is enriched in the leading edges of cSCC and functions as a hub for intercellular communications within a fibrovascular niche. Consistently, we observed a significant enrichment of TSKs in the tumor leading edges, where they colocalize with distinct TME cell types, such as fibroblasts and endothelial cells. This was further validated by the spatial distances between cell type pairs (heatmap), where TSK-fibroblasts was determined to be in the "near" group and TSK-endothelial cells was determined to be in the "medium" group (boxplot).
Next, we investigated the LRIs within the TSK-fibrovascular TME. We observed that TSKs are engaged in extensive interactions with distinct stromal cell types in the TME.
For example, TSKs may modulate cancer-associated fibroblasts (CAFs) through several ligand-receptor pairs in the leading edges, including MDK-LRP1, CCL5-ACKR4 and VEGFA-NRP2. Moreover, we observed that TGFB1, a known CAF activator gene that is mainly expressed in TSKs in the leading edges, may participate in the induction of CAFs. These results are consistent with previous findings.
