Immune-phenotyping of pleomorphic dermal sarcomas suggests this entity as a potential candidate for immunotherapy

Pleomorphic dermal sarcomas (PDS) are sarcomas of the skin with local recurrences in up to 28% of cases, and distant metastases in up to 20%. Although recent evidence provides a strong rational to explore immunotherapeutics in solid tumors, nothing is known about the immune environment of PDS.

In the current study, a comprehensive immune-phenotyping of 14 PDS using RNA and protein expression analyses, as well as quantitative assessment of immune cells using an image-analysis tool was performed.

Three out of 14 PDS revealed high levels of CD8-positive tumor-infiltrating T-lymphocytes (TILs), also showing elevated levels of immune-related cytokines such as IL1A, IL2, as well as markers that were very recently linked to enhanced response of immunotherapy in malignant melanoma, including CD27, and CD40L. Using a multivariate analysis, we found a number of differentially expressed genes in the CD8-high group including: CD74, LYZ and HLA-B, while the remaining cases revealed enhanced levels of immune-suppressive cytokines including CXCL14. The "CD8-high" PDS showed strong MHC-I expression and revealed infiltration by PD-L1-, PD-1- and LAG-3-expressing immune cells. Tumor-associated macrophages (TAMs) predominantly consisted of CD68 + , CD163 + , and CD204 + M2 macrophages showing an accentuation at the tumor invasion front.

Together, we provide first explorative evidence about the immune-environment of PDS tumors that may guide future decisions whether individuals presenting with advanced PDS could qualify for immunotherapeutic options.