Working Paper Article Version 1 This version is not peer-reviewed

Cancer Testis Antigens and Immunotherapy: Expression of PRAME and NY-ESO-1 Predicts Survival in Soft Tissue Sarcoma

Version 1 : Received: 22 July 2020 / Approved: 25 July 2020 / Online: 25 July 2020 (11:23:54 CEST)

A peer-reviewed article of this Preprint also exists.

Albertsmeier, M.; Altendorf-Hofmann, A.; Lindner, L.H.; Issels, R.D.; Kampmann, E.; Dürr, H.-R.; Schubert-Fritschle, G.; Angele, M.K.; Kirchner, T.; Jungbluth, A.A.; et al. Cancer Testis Antigens and Immunotherapy: Expression of PRAME Is Associated with Prognosis in Soft Tissue Sarcoma. Cancers 2020, 12, 3612, doi:10.3390/cancers12123612. Albertsmeier, M.; Altendorf-Hofmann, A.; Lindner, L.H.; Issels, R.D.; Kampmann, E.; Dürr, H.-R.; Schubert-Fritschle, G.; Angele, M.K.; Kirchner, T.; Jungbluth, A.A.; et al. Cancer Testis Antigens and Immunotherapy: Expression of PRAME Is Associated with Prognosis in Soft Tissue Sarcoma. Cancers 2020, 12, 3612, doi:10.3390/cancers12123612.

Abstract

Background: PRAME, NY-ESO-1 and SSX2 are cancer testis antigens (CTAs), which in normal tissues 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-characterized cohort soft tissue sarcomas (STS). Methods: On protein level, we examined PRAME, NY-ESO-1 and SSX2 expression in tumour tissues of 249 STS using immunohistochemistry. We correlated expression levels with clinicopathological parameters including Tumour-infiltrating lymphocyte (TIL) counts, grading and long- term survival. 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 low grade (G2 vs G3, p=0.029). Both PRAME and NY-ESO-1 expression was more frequent in STS with low TILs counts. Conclusions: CTAs PRAME, NY-ESO-1 and SSX2 show distinct expression patterns in different STS subtypes. These results may guide future immunotherapeutic approaches in STS.

Keywords

soft tissue sarcoma; human; cancer/testis antigens; PRAME; NY-ESO-1; SSX2; biomarker; tumor infiltrating lymphocytes; immunohistochemistry

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Comments (0)

Comment 1
Received: 30 July 2020
Commenter: Shibani Pokras
The commenter has declared there is no conflict of interests.
Comment: Thanks for sharing this very interesting paper in a rare population. It would be helpful to understand what proportion of NY-ESO high expressors had synovial sarcoma, as the proportion of NY-ESO expression appears to be quite low when looking at other studies (as you have noted in the Discussion). Figure 2 notes a univariate analysis was conducted to examine the relationship between NYESO and STS, however, given that there may be differences in several other prognostic factors between high and low expressors that are driving the differences, I'm wondering if a multivariable analysis can be presented?
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