Clinical Roles of Increased Populations of Foxp3+CD4+ T Cells in Peripheral Blood from Advanced Pancreatic Cancer Patients

Abstract

Foxp3CD4 T cells are good markers for metastasis detection in PC patients and more accurate than other conventional tumor markers, especially at advanced stages of the disease.

Peripheral Tr1 and Foxp3+ Treg as Markers of Recurrent Malignancies in Patients with Hepato-Biliary Pancreatic Cancers

“…We previously showed that Foxp3 + Treg populations in peripheral blood can reflect the pathological aggressiveness of pancreatic ductal carcinomas and IPMNs (4,12). The numbers of Foxp3 + T cells were found to be increased in immune cells infiltrating pancreatic cancers and in draining lymph nodes (7,22), however, the mechanism by which Foxp3+Treg populations are expanded in peripheral blood from the tumor environment remained unclear (23).…”

“…Blood samples were withdrawn from patients at the time of normal laboratory testing and before any treatment, including surgery and radiation and/or chemotherapy. T cells populations were analyzed by FACScan, as described (4,5). Briefly, peripheral blood mononuclear cells were isolated from these samples by centrifugation of 2 ml blood plus 4 ml Lymphoprep™ (AXIS-SHIELD, Oslo, Norway) at 1,800 rpm for 20 min at room temperature, after hematolysis of red blood cells with 4 ml 0.9% NH 4 Cl.…”

“…T cells populations were analyzed by FACScan, as described (4,5). Briefly, peripheral blood mononuclear cells were isolated from these samples by centrifugation of 2 ml blood plus 4 ml Lymphoprep™ (AXIS-SHIELD, Oslo, Norway) at 1,800 rpm for 20 min at room temperature, after hematolysis of red blood cells with 4 ml 0.9% NH 4 Cl. To these cell pellets, antibodies to CD4 (APC-conjugated anti-human CD4; e-Bioscience, San Diego, CA, USA) and anti-CD25 (FITC-conjugated anti-human CD25; eBioscience, San Diego, CA, USA) for Fop3 + Treg analysis, or with antibodies to CD4 (APC-conjugated anti-human CD4; e-Bioscience, San Diego, CA, USA), CD49b (PE-conjugated anti-human CD49b, PIE6-C5; BioLegend, San Diego, CA, USA) and anti-LAG3 (FITCconjugated anti-human LAG3, 17B4; AdipoGen, San Diego, CA, USA) for Tr1 analysis were added.…”

“…Populations of peripheral Foxp3 + Tregs were found to be greater in pancreatic cancer patients than in healthy controls, with peripheral Foxp3 + Treg populations strongly correlating with TMN classifications (4). In addition, peripheral Foxp3 + Treg populations were found to significantly correlate with the pathological aggressiveness of intraductal papillary mucinous neoplasms (IPMNs), a correlation dependent on Notch signaling (5).…”

Pancreatic carcinoma development: new etiological and pathogenetic evidence

“…114 On the other hand, Hiraoka reported that the prevalence of CD4 + Foxp3 + T cells, infiltrating pancreatic cancer tissue and regional lymph nodes, increases during the progression of this tumor, ranging from precursor lesions, such as PanINs and intraductal-papillary mucinous neoplasia, to invasive carcinoma. A high prevalence of these Treg subsets predicts a poor prognosis.…”