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

Abstract

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 1 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 1 primary TILs of stage 3 patients with distant metastases was positively correlated with their overall survival. To evaluate whether CD8 1 effector T cells are activated or differentiated, flow cytometric analysis of peripheral blood mononuclear cells (PBMC) was performed. The percentages of CD8 1 T cells producing IFN-c in PBMC were significantly higher in patients with angiosarcoma (n 5 10) compared not only with that of healthy controls (n 5 20) but also patients with advanced melanoma (n 5 11). These results suggest that anti-tumor immunity is clinically relevant in angiosarcoma.

Infiltration of PD-1-positive cells in combination with tumor site PD-L1 expression is a positive prognostic factor in cutaneous angiosarcoma

“…We classified patient groups into three stages as reported previously, stage I for patients with local tumors, stage II for patients with lymph node involvement, and stage III for patients with distant metastases. 11,32 Computed tomography (CT) was used to detect metastasis of lymph nodes and distant organs. 11 out of 106 samples were taken after systemic treatments including taxanes and pasopanib.…”

“…Fujii et al reported that antitumor immunity with CD8 C T cells in tumor-infiltrating lymphocytes (TILs) is important to prevent the progression of CAS. 11 Certain types of human cancers express programmed cell death-1 ligand-1 (PD-L1) on the cell surface, which enables cancer cells to escape immune reactions by binding the inhibitory receptor programmed cell death-1 (PD-1) on T cells. 12 Clinically, tumor PD-L1 expression affects patients' prognosis, and anti-PD-1-antibody administration has shown significant efficacy in treating several malignancies.…”

PDL1 expression is a poor-prognosis factor in soft-tissue sarcomas

“…12 Patients with immune deficiencies, such as organ transplant patients, show an increased incidence of sarcomas. 13 Lymphocytic infiltration of the tumor was demonstrated in sarcomas, with positive prognostic value in cutaneous angiosarcomas, 14 negative prognostic value in STS or liposarcomas, 8,[15][16][17][18][19] or no prognostic value in MPNST. 20 An unfavorable prognostic role of tumor-associated macrophages was reported in leiomyosarcomas 21 and myxoid liposarcomas.…”

Potential for immunotherapy in soft tissue sarcoma

“…Fujii et al characterized the T cells found in cutaneous angiosarcoma. 26 Both CD4 and CD8 T cells were identified in all tumors, including FoxP3 positive cells which may represent regulatory T cells. Higher frequencies of CD8 T cells were associated with improved overall and distant metastasis-free survival.…”