CD8⁺ tumor-infiltrating lymphocytes at primary sites as a possible prognostic factor of cutaneous angiosarcoma.
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.
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Hiroko
H
Fujii
Akiko
A
Arakawa
Daisuke
D
Utsumi
Shinji
S
Sumiyoshi
Yosuke
Y
Yamamoto
Akihiko
A
Kitoh
Masahiro
M
Ono
Yumi
Y
Matsumura
Mayumi
M
Kato
Keisuke
K
Konishi
Takeo
T
Shiga
Shigetoshi
S
Sano
Shimon
S
Sakaguchi
Aya
A
Miyagawa-Hayashino
Kenzo
K
Takahashi
Hiroshi
H
Uezato
Yoshiki
Y
Miyachi
Miki
M
Tanioka
D000368:Aged; D000369:Aged, 80 and over; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D006394:Hemangiosarcoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000276:immunology / Q000378:metabolism; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D015704:CD4 Antigens; D016827:CD8 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D019394:Ki-67 Antigen; D007371:Interferon-gamma
cutaneous angiosarcoma; prognosis; tumor-infiltrating lymphocytes