Abstract A24: Tumor immune profiling suggests synovial sarcoma but not desmoplastic small round cell tumor may respond to cancer immunotherapies
Authors: Mary Frances Wedekind, Kellie Haworth, Michael Arnold, Joseph Stanek, Timothy Cripe
Journal: Cancer Research (2018)

Abstract Background: Desmoplastic small round cell tumor (DSRCT) and synovial sarcoma are rare cancers, mainly affecting older children and young adults, with very poor survival rates. Other than surgery for localized disease, conventional treatments such as chemotherapy and radiotherapy have not had significant impacts on outcomes. Whether immunotherapeutic approaches may be useful for these diseases is unknown. Results from other cancer subtypes indicate that knowledge of the expression of relevant immunologic molecules and intratumoral immune cell infiltrates may be predictive of prognosis and therapeutic response. Objective: To characterize the immune profiles of human DSRCT and synovial sarcoma tumors. Methods: This study was approved by the Nationwide Children’s Hospital Institutional Review Board. Using tissue microarrays of 9 DSRCT and 12 synovial sarcoma tumor samples, we detected tumoral HLA–A/B/C, beta-2-microglobulin (B2M), and PD-L1 expression, and quantified tumor-infiltrating lymphocytes expressing CD4, CD8, CD56, CD45RO, or FOXP3 by immunohistochemistry. We used staining intensity on a scale of 0-3 (absent= 0, weak= 1, moderate = 2, strong = 3) and percentage of tumor stained to determine HLA, B2M, and PD-L1 scores (range 0-300). We calculated the cytotoxic T lymphocyte (CTL) Target score as HLA score x B2M score/100 (range 0-900). All data were summarized descriptively and statistical comparisons were made using Mann-Whitney tests. Results: We found DSRCT diagnostic samples had higher HLA, CTL Target, and PD-L1 scores compared to recurrent samples (15, 17, and 16.7 versus 0, 0, and 3.3, respectively). We observed fewer CD8+ and CD45RO+ cells in relapsed samples compared to those obtained at diagnosis (35.3 versus 1.3/mm2 and 14.6 versus 4.7/mm2, respectively). We found no significant difference in CD56+ cell numbers (0.8 versus 0.7/mm2) at diagnosis or relapse. In synovial sarcomas, HLA and CTL Target scores decreased from diagnosis to recurrence (100 and 133.3 versus 81.7 and 78.3, respectively), while PD-L1 scores increased (10 versus 21.7). FOXP3+ cell numbers remained stable, while the numbers of CD56+ and CD45RO+ cells increased from diagnosis to recurrence (0 versus 0.6/mm2, 0.4 versus 2.6/mm2, 8.7 versus 13.1/mm2, respectively). Comparing synovial sarcoma to DSRCT, the HLA and CTL Target scores were statistically significantly different (95.8 versus 3.3, p = 0.0192; 98.3 versus 0, p= 0.0235, respectively). Conclusions: We found lower HLA scores, resulting in decreased CTL Target scores, in recurrent DSRCT and synovial sarcoma tumors compared with diagnostic samples. These results suggest that up-front, rather than second-line, CTL-based immunotherapeutic strategies may be beneficial, and that these tumors may evade antitumor immunity by downregulating HLA I. Low PD-L1 scores in both tumor types indicate potential lack of response to PD-1/PD-L1 axis immune checkpoint blockade. The low HLA scores and consistent presence of CD56+ cells in DSRCT samples suggest that NK cell-based immunotherapeutic modalities may be beneficial for these patients, though this conclusion is limited by the small sample size. We hypothesize that synovial sarcoma is more likely than DSRCT to benefit from CTL-based immunotherapies. However, we found wide heterogeneity in both tumor types, suggesting the need to develop and validate predictive biomarkers for individual patients. Citation Format: Mary Frances Wedekind, Kellie Haworth, Michael Arnold, Joseph Stanek, Timothy Cripe. Tumor immune profiling suggests synovial sarcoma but not desmoplastic small round cell tumor may respond to cancer immunotherapies [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr A24.