We described and compared the immune microenvironment in uterine (UL) and non-uterine (NUL) leiomyosarcomas, and evaluated the clinical impact in a group of patients enrolled in a randomised phase III trial comparing doxorubicin to doxorubicin+trabectedin as first-line therapy in advanced/metastatic tumors. The study group contained 53 UL and 63 NUL. By multiplex immunochemistry, we assessed the percentage of CD3+, CD20+, CD68+ and CD57+ cells in immune cells, in stroma and tumor. TILMs (lymphocytes + macrophages) was defined as the percentage of stromal area occupied by immune cells. P53expressionwas evaluated semi-quantitatively, from 1 to 3. In both subgroups, CD68 labeled 80% of immune-cells found in contact with tumor-cells. In the stroma, CD3+ cells were more frequent (45% in NUL, 30% in UL). CD20 and CD57 stained > 5% of all immune-cells. When comparing the subgroups, high-CD3 (>27,5%) was encountered more frequently in NUL than UL (p : 0,0369). Conversely, high-CD68 (>65%) was observed mostly in UL. Patients with high CD57 appeared to have a better prognosis in term of progression-free survival. Additionally, the therapy effect seemed to be more important in patients with low-P53 (>>30%). however, for all markers, there were no statistically significant associations with the outcomes/therapy response, regardless of group or type of treatment. Several differences have been identified between UL and NUL, with regard to the tumour-infiltrating immune cells. It seems that CD3 is more expressed in NUL. High CD57 values appeared to correlate with a better progression-free survival, but further investigation is needed to confirm these data. However, there is no suggestion that immune microenvironment or TILMS can be prognostic factors or predictive markers of response to therapy, be it doxorubcin alone or doxorubicin+trabectedin.
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Catherine Genestie (2024) studied this question.
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