Cancer Testis Antigens and Immunotherapy: Expression of PRAME Is Associated with Prognosis in Soft Tissue Sarcoma

Abstract

(1) Background: PRAME, NY-ESO-1, and SSX2 are cancer testis antigens (CTAs), which are expressed in testicular germ cells with re-expression in numerous cancer types. Their ability to elicit humoral and cellular immune responses have rendered them promising targets for cancer immunotherapy, but they have never been studied in a large and well-characterised cohort of soft tissue sarcomas (STS). (2) Methods: On a protein level, we examined PRAME, NY-ESO-1, and SSX2 expression in tumour tissues of 249 high-risk STS using immunohistochemistry. We correlated expression levels with clinicopathological parameters including tumour-infiltrating lymphocyte (TIL) counts, grading, and long-term survival. (3) Results: Expression of PRAME, NY-ESO-1, and SSX2 was observed in 25 (10%), 19 (8%), and 11 (4%) of 249 specimens with distinct patterns for histo-subtypes. Expression of PRAME was associated with shorter patient survival (p = 0.005) and higher grade (G2 vs. G3, p = 0.001), while NY-ESO-1 expression was correlated with more favourable survival (p = 0.037) and lower grade (G2 vs. G3, p = 0.029). Both PRAME and NY-ESO-1 expression were more frequent in STS with low TIL counts. In multivariate analysis, high PRAME and low SSX2 expression levels as well as metastatic disease and non-radical resections were independent predictors of shorter overall survival. (4) Conclusions: CTAs PRAME, NY-ESO-1, and SSX2 show distinct expression patterns in different STS subtypes. These results demonstrate their prognostic relevance and may guide future immunotherapeutic approaches in STS.

mRNA Network: Solution for Tracking Chemotherapy Insensitivity in Small-Cell Lung Cancer

“…It played an important role in the invasion [ 52 ] and metastasis [ 53 ] of lung cancer. For cancer patients, overexpression of PRAME was frequently correlated with poor prognosis [ 54 , 55 ]. Furthermore, the low expression of SERPING1 represented poor prognosis in prostate cancer [ 56 ].…”

Dedifferentiated melanoma with MDM2 gene amplification mimicking dedifferentiated liposarcoma

“…Although PRAME can be used to confirm the diagnosis of dedifferentiated or undifferentiated melanoma in the appropriate clinical setting, 8 the expression of this marker is nonspecific for melanocytic origin and can be seen in a range of sarcomas. 9 Hemminger et al 10 and others 11 demonstrated that 100% of MLs (including high-grade ML) showed strong and homogenous immunoreactivity for PRAME. A further study by Albertsmeier et al 9 demonstrated that sarcomas other than ML express PRAME: angiosarcoma (44%), malignant peripheral nerve sheath tumour (MPNST; 38%), synovial sarcoma (11%), undifferentiated pleomorphic sarcoma (UPS; 7%), leiomyosarcoma (6%) and DD-LPS (4%).…”

“…9 Hemminger et al 10 and others 11 demonstrated that 100% of MLs (including high-grade ML) showed strong and homogenous immunoreactivity for PRAME. A further study by Albertsmeier et al 9 demonstrated that sarcomas other than ML express PRAME: angiosarcoma (44%), malignant peripheral nerve sheath tumour (MPNST; 38%), synovial sarcoma (11%), undifferentiated pleomorphic sarcoma (UPS; 7%), leiomyosarcoma (6%) and DD-LPS (4%). 9 Therefore, we can conclude that although in this particular case PRAME could have been useful (not available in our laboratory before FISH was performed) to prove dedifferentiated melanoma, in the context of a sarcomatoid tumour, it cannot be reliably used in the differential diagnosis.…”

A novel immune-related gene signature predicting survival in sarcoma patients

“…Increasing evidence suggests that tumor-infiltrating immune cells determine the clinical outcome of immunotherapy in different sarcoma subtypes. 10 , 11 , 12 , 13 Immunosurveillance is mediated in part by two major groups of T cells (CD4+, CD8+), which play a pivotal role in tumor formation, tumor progression, and therapy. 14 Moreover, previous studies demonstrated that an abundance of specific T cell subsets exerts favorable effects on the immune status of patients, improving responses to anticancer treatment and, subsequently, prognosis.…”