Clinical Impact of the Immune Microenvironment in Spinal Chordoma: Immunoscore as an Independent Favorable Prognostic Factor

BACKGROUND Currently, clinical implications of immune system cells in chordoma remain to be elucidated. OBJECTIVE To characterize in situ immune cell infiltrates, the Immunoscore, and investigate their correlation with clinicopathologic data of spinal chordoma patients and outcome. METHODS Tumor-infiltrating lymphocytes (TILs) subtypes were assessed in 54 tumor specimens using immunohistochemistry for CD3, CD4, CD8, CD20, Foxp3, PD-1, and PD-L1. RESULTS Overall, immune cell infiltrates were present in all samples and there was low or moderate correlation among several TILs subsets. PD-1(+) TILs density, CD3(+), and CD8(+) TILs densities in the tumor interior (TI) subarea were associated with surrounding muscle invasion by tumor, whereas PD-L1(+) TILs showed inverse association with tumor pathological grade and stage. The density of PD-1(+) TILs, PD-L1(+) TILs, CD4(+) TILs, and CD3(+) TILs both in the TI and combined tumor regions (TI and invasion margin) were significantly associated with local recurrence-free survival and overall survival (OS). However, Foxp3(+) TILs (P=.024) and CD8(+) TILs evaluated in the TI (P<.001) only correlated with OS. The Immunoscore predicted less aggressive clinical features and favorable outcomes. Patients with an Immunoscore of 4 had a median OS of 128 mo, while I0 (Immunoscore of 0) patients survived only 27 mo. Multivariate analysis demonstrated that the Immunoscore was an independent favorable prognostic factor of both local recurrence-free survival (P=.026) and OS (P=.046). CONCLUSION Our data suggest a clinically relevant role of the immune microenvironment in spinal chordoma and identify the Immunoscore as promising prognostic marker.