Immune checkpoint inhibitors (ICIs), including anti-programmed death-1 (PD-1) antibodies, were recently reported to be effective against CAS. The tumor immune response in CAS is still unclear, however, and even the prognostic value of the expression of PD-L1 in CAS remains controversial. Some reports suggest that tertiary lymphoid structures (TLSs), defined as CD20-positive B cell follicles surrounded by CD3-positive T cells, are promising biomarkers that correlate with a better prognosis in several cancers, but their correlation with the prognosis in CAS is not yet established. In the present study, we investigated tumor immunity-related factors, including PD-L1 and TLSs, to clarify useful prognostic biomarkers in CAS. We examined 61 specimens from 31 patients diagnosed with CAS, and performed immunofluorescence staining for PD-L1, PD-1, CD8, CD3 and CD20. Expression of PD-L1 and infiltration of CD8 in primary lesions did not significantly correlate with the prognosis (log-rank test, p=0.678, p=0.876). The presence of TLSs was identified as clusters of CD20-positive cells surrounded by CD3-positive cells in 28 specimens from 15 cases. Only T cells in contact with B cells in the CD20-positive cell cluster expressed PD-1. Patients with at least one TLS in the primary lesion had a significantly better prognosis than those without TLSs (log-rank, p=0.0032). In multivariate analysis, only TLSs correlated with prognosis among the choice of treatment and other immunological markers (HR=0.197, 95% CI, 0.046-0.838, p=0.028). Significantly more TLSs were observed in poorly differentiated tumors compared to well-differentiated or moderately differentiated. (Fisher’s exact test, p=0.048). On the basis of these findings, the presence of TLSs appears to be a valuable prognostic biomarker for patients with CAS. The presence of TLSs also suggests that CAS is an immunologically hot tumor, similar to other carcinomas treated with ICIs. Knowledge of the presence or absence of TLSs might be useful for the treatment selection of immunotherapies targeting CAS.

ESDR275 - Tertiary lymphoid structures correlate with better prognosis in cutaneous angiosarcoma

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING