Expression of multiple immune checkpoint molecules on T cells in malignant ascites from epithelial ovarian carcinoma

  • Authors:
    • Yuichi Imai
    • Kosei Hasegawa
    • Hirokazu Matsushita
    • Nao Fujieda
    • Sho Sato
    • Etsuko Miyagi
    • Kazuhiro Kakimi
    • Keiichi Fujiwara
  • View Affiliations

  • Published online on: February 21, 2018     https://doi.org/10.3892/ol.2018.8101
  • Pages: 6457-6468
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Abstract

Expression of immune checkpoint molecules, including programmed cell death protein‑1 (PD‑1), has been reported on T cells in various types of cancer. However, the expression status of these molecules in the tumor microenvironment of epithelial ovarian cancer (EOC) has not yet been studied. A total of 54 cases of malignant ascites from patients with EOC were analyzed in the present study. The expression of PD‑1, lymphocyte‑activation gene‑3 (LAG‑3), T‑cell immunoglobulin and mucin-domain containing‑3 (TIM‑3) and B and T lymphocyte attenuator (BTLA) on cluster of differentiation (CD)4+ and CD8+ T cells in malignant EOC ascites were investigated using multicolor flow cytometric analysis. The expression of PD‑L1 in tumor cells, PD‑L2 in HLA‑DR‑positive cells and galectin‑9 in ascitic fluid was also analyzed. In addition, cytokine profiling of ascitic fluid was performed to understand the immune microenvironment of EOC. PD‑1, LAG‑3 TIM‑3, and BTLA were expressed on 65.8, 10.6, 4.3 and 37.6% of CD4+ T cells, and on 57.7, 5.0, 4.9 and 15.7% of CD8+ T cells, respectively. Programmed cell death protein-1 (PD‑1), LAG‑3 and BTLA were more frequently expressed on CD4+ compared with CD8+ T cells. The co‑expression of immune checkpoints was further investigated and results indicated that 39 (72.2%) and 37 patients (68.5%) expressed multiple immune checkpoints on CD4+ T cells and CD8+ T cells, respectively. In addition, lower levels of TNF‑α and interleukin‑6 in ascitic fluid were significantly associated with multiple immune checkpoint expression on CD8+ T cells. The present findings indicated that multiple immune checkpoint molecules were expressed on T cells in the EOC tumor microenvironment and the results may suggest the significance of simultaneous blockade of immune checkpoints to control EOC.
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May-2018
Volume 15 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Imai Y, Hasegawa K, Matsushita H, Fujieda N, Sato S, Miyagi E, Kakimi K and Fujiwara K: Expression of multiple immune checkpoint molecules on T cells in malignant ascites from epithelial ovarian carcinoma. Oncol Lett 15: 6457-6468, 2018.
APA
Imai, Y., Hasegawa, K., Matsushita, H., Fujieda, N., Sato, S., Miyagi, E. ... Fujiwara, K. (2018). Expression of multiple immune checkpoint molecules on T cells in malignant ascites from epithelial ovarian carcinoma. Oncology Letters, 15, 6457-6468. https://doi.org/10.3892/ol.2018.8101
MLA
Imai, Y., Hasegawa, K., Matsushita, H., Fujieda, N., Sato, S., Miyagi, E., Kakimi, K., Fujiwara, K."Expression of multiple immune checkpoint molecules on T cells in malignant ascites from epithelial ovarian carcinoma". Oncology Letters 15.5 (2018): 6457-6468.
Chicago
Imai, Y., Hasegawa, K., Matsushita, H., Fujieda, N., Sato, S., Miyagi, E., Kakimi, K., Fujiwara, K."Expression of multiple immune checkpoint molecules on T cells in malignant ascites from epithelial ovarian carcinoma". Oncology Letters 15, no. 5 (2018): 6457-6468. https://doi.org/10.3892/ol.2018.8101