Spontaneous apoptosis of circulating T-lymphocytes and its correlation to their prolactin receptor expression and prolactin plasma levels in patients with breast cancer

bcr408 BCJ Meeting abstract Spontaneous apoptosis of circulating T-lymphocytes and its correlation to their prolactin receptor expression and prolactin plasma levels in patients with breast cancer Bauernhofer T Friebe-Hoffmann U Hoffmann T Dworacki G Vonderhaar B Whiteside TL

University of Pittsburgh Cancer Institute, Pittsburgh, Philadelphia; and National Cancer Institute, NHI, Bethesda, Maryland, USA

Breast Cancer Res 23rd Congress of the International Association for Breast Cancer Research Meeting abstracts 23rd Congress of the International Association for Breast Cancer Research Düsseldorf, Germany

13–16 June 2001

1465-5411 2001 3 Suppl 1 A8 10.1186/bcr408 10 5 2001 29 5 2001 2001 BioMed Central Ltd bcr-3-s1-a8

We have previously shown that a higher percentage of circulating CD3⁺ T lymphocytes undergo spontaneous apoptosis in cancer patients as compared with normal controls. Prolactin (PRL) has been reported to inhibit apoptosis in various cell types, including a Nb2 rat lymphoma cell line. In addition, there is evidence that the human PRL-antagonist hPRL-G129R induces apoptosis in breast cancer cell lines. We investigated a possible relationship between prolactin receptor (PRL-R) expression and apoptosis of CD3⁺ T lymphocytes, as well as PRL plasma levels, in patients with breast cancer. Peripheral blood mononuclear cells of patients (n = 11) and sex-matched normal controls (n = 12) were stained with AnnexinV, anti-Fas mAb (CD95), mouse antihuman PRL-R mAb B6.2, anti-CD3 mAb and respective isotype control mAbs. Multicolor flow cytometry was used to compare expression of these markers on T cell. In patients, 37 ± 19% (median ± SD) of CD3⁺ cells bound AnnexinV, marking early apoptosis of T lymphocytes compared with 17 ± 10% in controls (P <0.004). Furthermore, 82 ± 15% of the CD3⁺ T cells were Fas⁺ in patients, compared with 51 ± 9% in controls (P <0.0001). All CD3⁺ T lymphocytes were positive for PRL-R expression in breast cancer patients, as well as in normal control individuals. The mean fluorescence intensity of PRL-R on T lymphocytes of breast cancer patients was 106-172 (median 119) compared with 87-176 (median 123), suggesting no difference in PRL-R expression on T lymphocytes in patients versus controls. PRL plasma levels were comparable in patients and normal controls (4.8 ± 3.4 ng/ml versus 9.8 ± 4.6 ng/ml). In concordance with these findings, PRL was not able to inhibit the onset of apoptosis of Jurkat cells, a thymic lymphoma cell line, incubated with Fas cross-linking CH-11 mAb. These results indicate that PRL/PRL-R might not be involved in modulating Fas/Fas ligand interactions, which are, in part, responsible for apoptosis of T lymphocytes, leading to excessive turnover of T cells in the circulation of patients with breast cancer.