Role of plasmacytoid dendritic cells and inducible costimulator‐positive regulatory T cells in the immunosuppression microenvironment of gastric cancer

Abstract

Regulatory T cells (Tregs) and plasmacytoid dendritic cells (pDCs) play important roles in the immune escape of cancer. In this study, we investigated pDCs and pDC-induced inducible costimulator (ICOS)+ Treg populations in peripheral blood from gastric cancer (GC) patients and healthy donors by flow cytometry. The distribution of these cells in carcinoma tissue, peritumor tissue, and normal gastric mucosa was detected by immunohistochemistry. Plasma and tissue concentration of the cytokines such as interleukin-10 and transforming growth factor-β1 were also measured. We found that the numbers of pDCs, Tregs, and ICOS+ Tregs in peripheral blood were increased in GC patients compared with healthy donors. In tissue, Tregs and ICOS+ Tregs were found distributing mainly in carcinoma tissue, whereas pDCs were mainly found in peritumor tissue. Moreover, the Foxp3+ICOS+/Foxp3+ cell ratio in carcinoma and peritumor tissue were higher than that in normal tissue. There were more ICOS+ Tregs in tumor and peritumor tissue of late-stage GC patients. There was a positive correlation between pDCs and ICOS+ Tregs in peripheral blood and peritumor tissue from GC patients. In conclusion, pDCs may play a potential role in recruiting ICOS+ Tregs, and both participate in the immunosuppression microenvironment of GC.

ICOS+Foxp3+TILs in gastric cancer are prognostic markers and effector regulatory T cells associated withHelicobacter pylori

“…The inhibition of inflammatory responses leads to chronic infection and the development of atrophic gastritis, which may progress to gastric cancer . Although Foxp3 + Tregs in tumor tissues have been correlated with tumor progression in most of types of solid cancers including gastric cancer, we showed, in the present study, a negative correlation between Foxp3 + cells in tumor tissues and the clinical stages of gastric cancer, while ICOS + Foxp3 + cells were strongly associated with the progression of gastric cancer, ICOS‐L and TLR9 in pDCs, and H. pylori infection. The weak expression of ICOS on CD45RA + CD8 + TILs indicates that ICOS has potential as a novel single prognostic biomarker for patients with gastric cancer as well as a marker for eTregs in gastric cancer tissues.…”

“…identified ICOS + Foxp3 + cells and pDCs in ovarian cancer, the numbers of which correlated with each other, as strong predictors for tumor progression, and also showed that the proliferation of ICOS + Tregs obtained from ovarian cancer tissues was blocked by the addition of anti‐ICOS‐L Ab to a culture with ICOS‐L + pDCs . In a previous study on gastric cancer, ICOS + Foxp3 + cells and pDCs were analyzed using IHC with fixed tumor tissue, and the interaction between ICOS + Foxp3 + cells and pDCs was analyzed by a flow cytometer with PBMCs . In this study, freshly isolated ICOS + Foxp3 + cells and pDCs from gastric cancer tissues were applied to frequency and expression studies and agonistic rICOS‐L Ig was used in induction assays of ICOS + Foxp3 + cells and CMV‐, Melan‐A‐specific T cells.…”

Gastric cancer patients have elevated plasmacytoid and CD1c+ dendritic cells in the peripheral blood

“…pDCs were identified as SSC (13). Although using different surface markers to detect pDCs, the results of these two studies showed a higher proportion of circulating pDCs in patients with gastric cancer, compared with that in healthy controls.…”

TGF-β1 contributes to CD8+ Treg induction through p38 MAPK signaling in ovarian cancer microenvironment

“…Tregs are highly enriched in the tumor microenvironment and are pivotal mediators of immune suppression [4]. We and others have previously demonstrated that Treg populations are elevated in patients with OC and other tumors [5–7]. Furthermore, the presence of tumor-infiltrating Tregs correlates with poor prognosis in many tumor types [8–10].…”