CD8⁺ tumor-infiltrating lymphocytes at primary sites as a possible prognostic factor of cutaneous angiosarcoma

Int J Cancer. 2014 May 15;134(10):2393-402. doi: 10.1002/ijc.28581. Epub 2013 Nov 18.


Tumor-infiltrating lymphocytes (TILs) have been reported as a prognostic factor in various cancers and are a promising target for immunotherapy. To investigate whether TILs have any impact on the prognosis of angiosarcoma patients, 55 non-treated patients (40 patients at stage 1 with cutaneous localized tumors, 4 patients at stage 2 with lymph node metastases and 11 patients at stage 3 with distant metastases) with angiosarcoma were evaluated retrospectively by immunohistochemistry stained CD4, CD8, FOXP3 and Ki67. The Kaplan-Meier method was used to estimate overall survival with patients at stage 1. Survival differences were analyzed by the log-rank test. Patients with higher numbers of CD8(+) TILs in their primary tumors survived significantly longer compared with patients with lower values. Moreover, the number of CD8 in TILs was positively correlated with a distant metastasis-free period. The total number of primary TILs (CD4 plus CD8) and CD8(+) primary TILs of stage 3 patients with distant metastases was positively correlated with their overall survival. To evaluate whether CD8(+) effector T cells are activated or differentiated, flow cytometric analysis of peripheral blood mononuclear cells (PBMC) was performed. The percentages of CD8(+) T cells producing IFN-γ in PBMC were significantly higher in patients with angiosarcoma (n = 10) compared not only with that of healthy controls (n = 20) but also patients with advanced melanoma (n = 11). These results suggest that anti-tumor immunity is clinically relevant in angiosarcoma.

Keywords: cutaneous angiosarcoma; prognosis; tumor-infiltrating lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • CD4 Antigens / immunology
  • CD4 Antigens / metabolism
  • CD8 Antigens / immunology
  • CD8 Antigens / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / pathology
  • Female
  • Forkhead Transcription Factors / immunology
  • Forkhead Transcription Factors / metabolism
  • Hemangiosarcoma / immunology*
  • Hemangiosarcoma / metabolism
  • Hemangiosarcoma / pathology
  • Humans
  • Immunohistochemistry
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Kaplan-Meier Estimate
  • Ki-67 Antigen / immunology
  • Ki-67 Antigen / metabolism
  • Leukocyte Count
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / pathology
  • Lymphatic Metastasis
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Retrospective Studies
  • Skin Neoplasms / immunology*
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology


  • CD4 Antigens
  • CD8 Antigens
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Ki-67 Antigen
  • Interferon-gamma