Association of tumour‐infiltrating regulatory T cells with adverse outcomes in dogs with malignant tumours

Abstract

Regulatory T cells (Tregs) infiltrate into a variety of tumour tissues and associate with poor prognosis in humans. However, data on association of Treg infiltration with prognosis is limited in canine tumours. The purpose of this study was to examine the number of tumour-infiltrating Tregs and its association with overall survival (OS) in dogs with malignant tumours. The following 168 canine tumours were included: 37 oral malignant melanomas (OMMs); 14 oral squamous cell carcinomas (OSCCs); 16 pulmonary adenocarcinomas (PAs); 37 mammary carcinomas (MCs); 36 mast cell tumours (MCTs) and 28 hepatocellular carcinomas (HCCs). Normal tissues were obtained from 8 healthy dogs as controls. The number of forkhead box P3 (Foxp3)-positive Tregs in intratumoral and peritumoral areas was investigated by immunohistochemistry. OS was compared between high and low Treg groups. The number of intratumoral and peritumoral Foxp3-positive Tregs was significantly higher in OMM, OSCC, PA and MC compared with each normal tissue. There were few Foxp3-positive Tregs in MCT and HCC. With intratumoral Tregs, the OS in the high Treg group was significantly shorter than that in the low Treg group in OMM, OSCC and PA. With peritumoral Tregs, there was no significant difference for OS between the 2 groups in each tumour type. These results suggest that Tregs infiltrate into a variety of canine tumours and the abundance of Tregs are associated with poor prognosis in some solid tumour types.

In-situ vaccination using focused ultrasound heating and anti-CD-40 agonistic antibody enhances T-cell mediated local and abscopal effects in murine melanoma

“…Importantly, the increase of M1 macrophages in the FUS40 tumor was not associated with significant changes in the Treg populations ( Figure S2). Tregs infiltrate tumors in response to chemokines secreted in the tumor microenvironments by TAMs (e.g., IL10, a cytokine produced by tumor macrophages) and can inhibit cancer cell cytotoxicity [55][56][57]. Our data suggest that FUS40 induce the polarization of macrophages without altering the Tregs.…”

Assessment of postoperative adjuvant treatment using toceranib phosphate against adenocarcinoma in dogs

“…The HIF‐1α + cells were classified as tumor cells in which the nucleus, cytoplasm or both was distinctively stained for HIF‐1α 19,20 . Regulatory T‐cells were defined as cells with typical lymphocyte morphology and Foxp3 staining in the nucleus but not the cytoplasm 21 . Regulatory T‐cells were quantified in 2 different compartments: the intra‐tumoral area (defined as the area within nests composed of >5 tumor cells) and the peritumoral area (the area outside tumor cell nests), as reported in a previous study 21 .…”

“…Regulatory T‐cells were defined as cells with typical lymphocyte morphology and Foxp3 staining in the nucleus but not the cytoplasm 21 . Regulatory T‐cells were quantified in 2 different compartments: the intra‐tumoral area (defined as the area within nests composed of >5 tumor cells) and the peritumoral area (the area outside tumor cell nests), as reported in a previous study 21 . Ten high power fields (HPFs) were selected in sites containing >50% tumor cells, and the intratumoral and peritumoral Tregs were counted in each field.…”

T lymphocytes related biomarkers for predicting immunotherapy efficacy in non‑small cell lung cancer (Review)

“…Patients with a high proportion of PD-L1 high CD25 + CD4 + TILs have a favorable response (45). However, some studies have failed to identify an association between the density of FOXP3 and the prognosis of patients in operable NSCLC (40,46,47). A study including 80 patients with NSCLC demonstrated that improved OS is associated with an increased number of FOXP3 + Tregs in tumor stroma.…”