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Letter to the Editor| Volume 103, ISSUE 1, P57-59, July 2021

Tertiary lymphoid structures correlate with better prognosis in cutaneous angiosarcoma

      Cutaneous angiosarcoma (CAS) is a rare malignant sarcoma for which there is no effective treatment. The prognosis is extremely poor, and the development of novel therapies is crucial. In general, soft tissue sarcomas are considered immunologically cold, but immune checkpoint inhibitors (ICIs), including anti-programmed death-1 (PD-1) antibodies, were recently reported to be effective against CAS [
      • Hofer S.
      • Zeidler K.
      • Schipf A.
      • Kempf W.
      • Zimmermann D.
      • Aebi S.
      Angiosarcoma of the scalp responding to nivolumab: a case report.
      ,
      • Florou V.
      • Rosenberg A.E.
      • Wieder E.
      • Komanduri K.V.
      • Kolonias D.
      • Uduman M.
      • Castle J.C.
      • Buell J.S.
      • Trent J.C.
      • Wilky B.A.
      Angiosarcoma patients treated with immune checkpoint inhibitors: a case series of seven patients from a single institution.
      ]. In most malignant tumors, high expression of programmed death-ligand 1 (PD-L1) is associated with a poor prognosis and PD-1/PD-L1 blockade is therefore expected to produce successful results. 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 [
      • Shimizu A.
      • Kaira K.
      • Okubo Y.
      • Utsumi D.
      • Yasuda M.
      • Asao T.
      • Nishiyama M.
      • Takahashi K.
      • Ishikawa O.
      Positive PD-L1 expression predicts worse outcome in cutaneous angiosarcoma.
      ,
      • Honda Y.
      • Otsuka A.
      • Ono S.
      • Yamamoto Y.
      • Seidel J.A.
      • Morita S.
      • Hirata M.
      • Kataoka T.R.
      • Takenouchi T.
      • Fujii K.
      • et al.
      Infiltration of PD-1-positive cells in combination with tumor site PD-L1 expression is a positive prognostic factor in cutaneous angiosarcoma.
      ]. 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, including malignant melanoma and sarcomas, but their correlation with the prognosis in CAS is not yet established [
      • Cabrita R.
      • Lauss M.
      • Sanna A.
      • Donia M.
      • Larsen M.S.
      • Mitra S.
      • Johansson I.
      • Phung B.
      • Harbst K.
      • Vallon-Christersson J.
      • van Schoiack A.
      • Lövgren K.
      • Warren S.
      • Jirström K.
      • Olsson H.
      • Pietras K.
      • Ingvar C.
      • Isaksson K.
      • Schadendorf D.
      • Schmidt H.
      • Bastholt L.
      • Carneiro A.
      • Wargo J.A.
      • Svane I.M.
      • Jönsson G.
      Tertiary lymphoid structures improve immunotherapy and survival in melanoma.
      ,
      • Petitprez F.
      • de Reyniès A.
      • Keung E.Z.
      • Chen T.W.
      • Sun C.M.
      • Calderaro J.
      • et al.
      B cells are associated with survival and immunotherapy response in sarcoma.
      ]. The presence of TLSs is thought to help promote anti-tumor immunity, and tumors with TLS are more responsive to ICIs than those without TLSs [
      • Helmink B.A.
      • Reddy S.M.
      • Gao J.
      • Zhang S.
      • Basar R.
      • Thakur R.
      • et al.
      B cells and tertiary lymphoid structures promote immunotherapy response.
      ]. The present study investigated tumor immunity-related factors, including PD-L1 and TLSs, to clarify useful prognostic biomarkers in CAS.
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