Publications

Clues for Immunotherapy Options in Intimal Sarcoma

Intimal sarcomas are rare, aggressive soft tissue tumors for which there are limited effective treatment options. Immunomodulatory therapy, particularly targeting of the PD-1/PD-L1 axis has revolutionized the field of oncology and become a cornerstone of treatment for some solid tumors, but remains exploratory in most sarcomas. Most large trials for immunotherapy in sarcomas do not include many intimal sarcomas due to their rarity. We sought to investigate whether the histologic tumor microenvironment of intimal sarcomas could yield clues to whether intimal sarcomas might be a subset of sarcomas that are amenable to treatment with immunomodulatory therapy. To address this, we examined the immune infiltrates and expression of immunomodulatory checkpoint proteins in seventeen specimens from seven (7) intimal sarcoma patients. All specimens displayed an active tumor immune microenvironment with infiltration by immune cells, including CD8+ T cells, that was balanced by immunoregulatory forces in the form of T regulatory cells and immune checkpoint proteins including PD-L1 and LAG3.  PD-L1 expression correlated with higher densities of CD8+ and FOXP3+ cells, suggesting an adaptive pattern of immune resistance, in which an initial active immune response, often rich with effector CD8 T cells producing IFN-gamma, “turns on” the expression of immunosuppressive and regulatory pathways such as the PD-L1/PD-1 axis. If such an effective immune reaction was initially present in intimal sarcoma, but blunted by checkpoint inhibitor expression, this suggests that targeting of those pathways might be fruitful in these tumors. Our findings would support further investigation of immune-based therapeutic interventions in intimal sarcomas as well as further studies of the microenvironment of other individual soft tissue sarcomas to allow for development of more guided and precise therapy.