Immunological and mutational characterization of non-uterine leiomyosarcoma: A pilot study.

Abstract

e22529 Background: Data from many studies in cancer studies suggest that factors such as expression of PD-L1, tumor infiltrating lymphocytes (TILs) and high mutational burden (TMB) in the tumor cells are connected with better response to immune check-point blockage and may have prognostic value. Little is known about those factors in other neoplasms. Methods: In this retrospective study, we have included 31 patients with leiomyosarcoma (LMS) localized on extremity (21) or in retroperitoneal space (10) treated in our center between 2002-2018 with available biopsy specimens obtained before treatment. Mean age was 58 year (SD: 17). Male:Female ratio was 0.82. 14(45%) lesions were deemed high-grade sarcomas. 3 patients had metastases at the time of diagnosis. Immunohistological assays for TILs, tumor associated macrophages (TAMs), PD-1 and PD-L1. TMB was assessed in Tumor Mutational Burden Panel in the formalin-fixed paraffin-embedded samples. 7 cases were excluded from TMB analysis due to poor specimens quality. Fisher exact test was used to compare discrete variables while Kaplan-Meier estimate and stratified log-rank test were used to examine impact of explored factors on survival. Results: The median overall survival in this cohort was 33.4 months (95% confidence intervals, CI: 32-NA). TMB > = 10 mutations/Mb was present in 33% high-grade (HG) and in 25% cases of low-grade (LG) LMS (p = 0.067). PD-L1 expression was present in 54% of HG lesions and in 31% of LG LMS (p = 0.43). TILs and TAMs were highly correlated and present in 40% and 50% of HG LMS and LG LMS respectively (p = 0.722). Among explored factors only TILs and TAMs had significant influence on survival as deemed by log-rank test stratified by tumor grade (p = 0.004) with 3-year survival rate of 100% in groups without TILs/TAMs regardless of grade and 0% in HG TILs/TAMs(+) group and 60% (95% CI: 31-100%) in LG TILs/TAMs(-) group. Conclusions: Significant percentage of LMS exhibit immunohistological and molecular traits which potentially are connected with good response to check-point blockage agents. The immunological infiltration of primary LMS may be strong negative prognostic factor, what is interesting in sarcoma. Future expansion of this study cohort is warranted.