Association between effector-type regulatory T cells and immune checkpoint expression on CD8 + T cells in malignant ascites from epithelial ovarian cancer

• Published in: BMC cancer 2022-04, Vol.22 (1), p.437-437, Article 437
• Main Authors: Sato, Sho, Matsushita, Hirokazu, Shintani, Daisuke, Kobayashi, Yukari, Fujieda, Nao, Yabuno, Akira, Nishikawa, Tadaaki, Fujiwara, Keiichi, Kakimi, Kazuhiro, Hasegawa, Kosei
• Format: Article
• Language: English
• Subjects: Antibodies; Antitumor activity; Ascites; Ascites - pathology; Cancer therapies; Carcinoma, Ovarian Epithelial - pathology; Care and treatment; CCR4; CD4 antigen; CD45RA antigen; CD8 antigen; CD8-Positive T-Lymphocytes; Chemokine receptors; Chemokines; Chemotherapy; Effector cells; Female; Flow cytometry; Foxp3 protein; Genetic aspects; Health aspects; Humans; Immune checkpoint; Immune response; Immunoregulation; Immunotherapy; Lymphocytes; Lymphocytes T; Lymphoma; Medical prognosis; Methods; Ovarian cancer; Ovarian Neoplasms - pathology; PD-1; PD-1 protein; Peritoneal Neoplasms - pathology; Programmed Cell Death 1 Receptor - genetics; Programmed Cell Death 1 Receptor - metabolism; Risk factors; T cells; T-Lymphocytes, Regulatory; Tregs; Tumor Microenvironment
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-022-09534-z

Regulatory T cells (Tregs) play an important role in the antitumor immune response in epithelial ovarian cancer (EOC). To understand the immune-inhibitory networks of EOC, we addressed the association between Tregs and immune checkpoint expression on T cells in the tumor microenvironment of EOC. A total of 41 patients with stage IIIC and IV EOC were included in the analysis. We harvested cells from malignant ascites and investigated them using multi-color flow cytometry. We categorized the Tregs into 3 groups: effector-type Tregs, naïve Tregs and non-Tregs, based on the expression patterns of CD45RA and Foxp3 in CD4 T cells. Furthermore, the relationships between the expression of various immune checkpoint molecules, such as PD-1, on CD8 T cells and each of the Treg subtypes was also evaluated. The median frequency of naïve Tregs, effector-type Tregs and non-Tregs were 0.2% (0-0.8), 2.0% (0-11.4) and 1.5% (0.1-6.3) in CD4 T cells of malignant ascites from EOC patients, respectively. A high frequency of effector-type Tregs was associated with high-grade serous carcinoma compared with the other histotypes. Patients with higher proportions of effector-type Tregs showed a trend towards increased progression-free survival. We also demonstrated a correlation between a higher proportion of effector-type Tregs and increased PD-1 expression on CD8 T cells. In addition, C-C chemokine receptor 4 expression was also observed in effector-type Tregs. These data suggest that multiple immune-inhibitory networks exist in malignant ascites from EOC patients, suggesting an approach towards combinational immunotherapies for advanced EOC patients.