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

Cancers

MartinK. Angele¹  Markus Albertsmeier¹  Annelore Altendorf-Hofmann²  Eric Kampmann³  LarsH. Lindner³  RolfD. Issels³  AchimA. Jungbluth⁴  Thomas Knösel⁵  Thomas Kirchner⁵  Gabriele Schubert-Fritschle⁶  Hans-Roland Dürr⁷ 

[1] Department of General, Visceral and Transplantation Surgery, University Hospital, Ludwig-Maximilians-Universität (LMU) Munich, Marchioninistr. 15, 81377 Munich, Germany;Department of General, Visceral and Vascular Surgery, Friedrich-Schiller Universität Jena, Am Klinikum 1, 07743 Jena, Germany;Department of Internal Medicine III, University Hospital, Ludwig-Maximilians-Universität (LMU) Munich, Marchioninistr. 15, 81377 Munich, Germany;Department of Pathology, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 1275, USA;Institute of Pathology, Ludwig-Maximilians-Universität (LMU) Munich, Thalkirchner Str. 36, 80337 Munich, Germany;Munich Cancer Registry (MCR) of the Munich Tumour Centre (TZM), Institute for Medical Information Processing, Biometry, and Epidemiology (IBE), University Hospital, Ludwig-Maximilians-Universität (LMU) Munich, Marchioninistr. 15, 81377 Munich, Germany;Musculoskeletal Oncology, Department of Orthopaedic Surgery, Physical Medicine and Rehabilitation, University Hospital, Ludwig-Maximilians-Universität (LMU) Munich, Marchioninistr. 15, 81377 Munich, Germany;

关键词: soft tissue sarcoma;    human;    cancer/testis antigens;    PRAME;    NY-ESO-1;    SSX2;   

DOI  :  10.3390/cancers12123612

来源: DOAJ

【 摘 要 】

(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.

【 授权许可】

Unknown