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

• Published in: Cancer Immunology, Immunotherapy Immunotherapy, 2019-06, Vol.68 (6), p.973-982
• Main Authors: Klein, Sebastian, Mauch, Cornelia, Wagener-Ryczek, Svenja, Schoemmel, Maximilian, Buettner, Reinhard, Quaas, Alexander, Helbig, Doris
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; B7-H1 Antigen - genetics; B7-H1 Antigen - immunology; B7-H1 Antigen - metabolism; Biomarkers, Tumor - genetics; Biomarkers, Tumor - immunology; Biomarkers, Tumor - metabolism; Cancer Research; CD163 antigen; CD223 antigen; CD27 antigen; CD40L protein; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cytokines; Cytokines - genetics; Cytokines - immunology; Cytokines - metabolism; Histocompatibility antigen HLA; Humans; Image processing; Immunology; Immunophenotyping - methods; Immunotherapy; Immunotherapy - methods; Interleukin 1; Interleukin 2; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Macrophages; Major histocompatibility complex; Medicine; Medicine & Public Health; Melanoma; Metastases; Middle Aged; Multivariate analysis; Neoplasm Recurrence, Local; Oncology; Original; Original Article; PD-1 protein; PD-L1 protein; Phenotyping; Programmed Cell Death 1 Receptor - genetics; Programmed Cell Death 1 Receptor - immunology; Programmed Cell Death 1 Receptor - metabolism; Ribonucleic acid; RNA; Sarcoma; Sarcoma - genetics; Sarcoma - immunology; Sarcoma - therapy; Skin; Skin Neoplasms - genetics; Skin Neoplasms - immunology; Skin Neoplasms - therapy; Solid tumors; Transcriptome - immunology; Tumors
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-019-02339-3

Background 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. Methods 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. Results 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. Conclusions 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.