TY - JOUR
T1 - Tumor-associated macrophages and the tumor immune microenvironment of primary and recurrent epithelial ovarian cancer
AU - Ojalvo, Laureen S.
AU - Thompson, Elizabeth D.
AU - Wang, Tian Li
AU - Meeker, Alan K.
AU - Shih, Ie Ming
AU - Fader, Amanda N.
AU - Cimino-Mathews, Ashley
AU - Emens, Leisha A.
N1 - Publisher Copyright:
© 2018
PY - 2018/4
Y1 - 2018/4
N2 - Tumor-infiltrating lymphocytes (TILs) are associated with better prognosis in newly diagnosed epithelial ovarian cancer (EOC), but clinical trials of immunotherapies in patients with heavily treated disease reveal limited activity. Understanding the tumor microenvironment (TME) of primary and recurrent EOC should guide future trials. Here, we evaluated the TME of paired primary and recurrent tumors (n = 17), and non-paired primary (n = 20) and recurrent (n = 15) tumors, for CD8+ T cells, FOXP3+ regulatory T cells (Tregs), CD68+ tumor-associated macrophages (TAMs), programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1). CD8+ T cells were similar in primary and recurrent tumors, but Tregs were higher in recurrent tumors (P =.0210). Higher TAM density (≥5%) associated with higher Tregs (P =.001) and CD8+ T cells (P <.001) in recurrent tumors, but only with higher Tregs in primary tumors (P =.02). TAM-dense recurrent tumors expressed PD-L1 on tumor and immune cells, whereas TAM-dense primary tumors expressed PD-L1 predominantly on immune cells. In survival analyses, higher Tregs in primary tumors correlated with decreased time to first recurrence (17.0 versus 28.5 months, P =.022). Conversely, higher Tregs in recurrent tumors correlated with longer overall survival (OS) from recurrence (median not met versus 20.0 months, P =.022). TAM density did not affect patient survival. However, patients with increased TAMs at recurrence (n = 5) had longer OS from recurrence compared to patients without increased TAMs (n = 12) (56.0 versus 20.0 months); with the small sample size, this did not reach statistical significance (P =.074). Further characterization of the evolution of the TME is warranted.
AB - Tumor-infiltrating lymphocytes (TILs) are associated with better prognosis in newly diagnosed epithelial ovarian cancer (EOC), but clinical trials of immunotherapies in patients with heavily treated disease reveal limited activity. Understanding the tumor microenvironment (TME) of primary and recurrent EOC should guide future trials. Here, we evaluated the TME of paired primary and recurrent tumors (n = 17), and non-paired primary (n = 20) and recurrent (n = 15) tumors, for CD8+ T cells, FOXP3+ regulatory T cells (Tregs), CD68+ tumor-associated macrophages (TAMs), programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1). CD8+ T cells were similar in primary and recurrent tumors, but Tregs were higher in recurrent tumors (P =.0210). Higher TAM density (≥5%) associated with higher Tregs (P =.001) and CD8+ T cells (P <.001) in recurrent tumors, but only with higher Tregs in primary tumors (P =.02). TAM-dense recurrent tumors expressed PD-L1 on tumor and immune cells, whereas TAM-dense primary tumors expressed PD-L1 predominantly on immune cells. In survival analyses, higher Tregs in primary tumors correlated with decreased time to first recurrence (17.0 versus 28.5 months, P =.022). Conversely, higher Tregs in recurrent tumors correlated with longer overall survival (OS) from recurrence (median not met versus 20.0 months, P =.022). TAM density did not affect patient survival. However, patients with increased TAMs at recurrence (n = 5) had longer OS from recurrence compared to patients without increased TAMs (n = 12) (56.0 versus 20.0 months); with the small sample size, this did not reach statistical significance (P =.074). Further characterization of the evolution of the TME is warranted.
KW - CD8+ T cells
KW - Ovarian cancer
KW - PD-1/PD-L1
KW - Regulatory T cells
KW - Tumor-associated macrophages
UR - http://www.scopus.com/inward/record.url?scp=85044102973&partnerID=8YFLogxK
U2 - 10.1016/j.humpath.2017.12.010
DO - 10.1016/j.humpath.2017.12.010
M3 - 文章
C2 - 29288043
AN - SCOPUS:85044102973
SN - 0046-8177
VL - 74
SP - 135
EP - 147
JO - Human Pathology
JF - Human Pathology
ER -