Flow cytometric analysis of tumour infiltrating lymphocytes in breast cancer

Whitford, P.; Mallon, Elizabeth; George, W.D.; Campbell, Angus

doi:10.1038/bjc.1990.419

Cited by 81 publications

(41 citation statements)

References 29 publications

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“…These T cells also had an activated phenotype, which was illustrated by their high expression of HLA-DR. These results are in line with previous reports on the activation marker HLA-DR from the surface of breast carcinoma (40) and RCC (41) TIICs. Moreover, the memory profile among T cells from TIICs is consistent with the intense CD45RO expression seen by Có zar et al (42) in RCC.…”

Section: Discussionsupporting

confidence: 83%

Human Activated T Lymphocytes Modulate IDO Expression in Tumors through Th1/Th2 Balance

Godin-Ethier

Pelletier

Hanafi

et al. 2009

The Journal of Immunology

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Previous cancer vaccination approaches have shown some efficiency in generating measurable immune responses, but they have rarely led to tumor regression. It is therefore possible that tumors emerge with the capacity to down-regulate immune counterparts, through the local production of immunosuppressive molecules, such as IDO. Although it is known that IDO exerts suppressive effects on T cell functions, the mechanisms of IDO regulation in tumor cells remain to be characterized. Here, we demonstrate that activated T cells can induce functional IDO expression in breast and kidney tumor cell lines, and that this is partly attributable to IFN-γ. Moreover, we found that IL-13, a Th2 cytokine, has a negative modulatory effect on IDO expression. Furthermore, we report IDO expression in the majority of breast and kidney carcinoma samples, with infiltration of activated Th1-polarized T cells in human tumors. These findings demonstrate complex control of immune activity within tumors. Future immune therapeutic interventions should thus include strategies to counteract these negative mechanisms.

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Section: Discussionsupporting

confidence: 83%

Human Activated T Lymphocytes Modulate IDO Expression in Tumors through Th1/Th2 Balance

Godin-Ethier

Pelletier

Hanafi

et al. 2009

The Journal of Immunology

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“…After an additional wash, the cells were resuspended in the same medium. Shimizu et Whitford et al, 1990;Viale et al, 1990) have not observed a subpopulation of double-positive T cells in TILs. In our system, IL-4 was used to establish TIL clones and it was thought that IL-4 augments the expression of the CD8 molecule in CD4+ T cells (Paliard et al, 1988).…”

Section: Il-2 Receptor Blocking Assaymentioning

confidence: 99%

Clonal and functional analysis for the augmentation of tumour-infiltrating lymphocytes by interleukin 4

Tsunoda

Tanimura²,

Yamaue³

et al. 1996

Br J Cancer

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Summary In the adoptive immunotherapy for cancer, the amounts of induced effector cells play a major role in improving therapeutic efficacy. We have already demonstrated that interleukin 4 (IL-4) augments proliferation of tumour-infiltrating lymphocytes (TILs) without altering the cytotoxic activity against autologous tumour cells. The present study is designed to investigate how IL-4 augments TILs by using established TIL clones in terms of IL-2/IL-2 receptor system. CD4+, CD8+ and CD4+CD8+ (double positive) TIL clones were established from cancer patients. At clonal level, IL-4 augmented the proliferation of IL-2-activated TIL clones irrespective of phenotypes. In order to clarify the mechanism of IL-4 at clonal level, the blocking assay by anti-IL-2 receptor a and P chain and binding assay of IL-2 on the cell surface and the measurement of the internalisation of IL-2 in the cell were performed. It was clarified that IL-4 up-regulated the IL-2 receptor and then augmented the action of IL-2 molecule on the cell surface stimulated by IL-4. Furthermore, binding IL-2 internalised rapidly into the cells. Thus, it is suggested that signal transduction is augmented and proliferation of TILs is enhanced by IL-4 via the action of IL-2/IL-2 receptor system. Keywords: interleukin 4; tumour-infiltrating lymphocyte; interleukin-2 receptor; scathard analysis Adoptive immunotherapy (AIT) using tumour-infiltrating lymphocytes (TILs) has been carried out by various investigators (Rosenberg et al., 1986;Topalian et al., 1988;Yamaue et al., 1990). The number of transferred TILs is a critical factor for obtaining a therapeutic effect. Interleukin 4 (IL-4) is a pleiotrophic cytokine that acts on various cell types (Paul and O'Hara, 1987; Swain et al., 1988;Spits et al., 1987;Horohov et al., 1988;Mitchell et al., 1989), and is produced by helper T cell type 2 (Mosmann et al., 1986). It has been reported that IL-4 mainly acts on B cells (BCGF, Bcell growth factor) (Howard et al., 1982), and that it can augment the cytotoxic activity of lymphokine-activated killer (LAK) cells in a murine model (Mule et al., 1987). Recently, it has been demonstrated that IL-4 inhibited LAK activity in humans (Nagler et al., 1988). However, it has been reported that IL-4 enhanced the proliferation of TILs obtained from different types of human tumours (Kawakami et al., 1988(Kawakami et al., , 1993. We have previously demonstrated that IL-4 augments the proliferation of interleukin 2 (IL-2)-activated TILs without inhibiting their cytotoxic activity against autologous tumour cells. Thus, the combination of IL-2 with IL-4 may lead to improved therapeutic efficacy of AIT using TILs (Tsunoda et al., 1992a). However, the mechanism of IL-4 on the augmentation of proliferation about TILs has not been clarified yet. In the present study, we demonstrated that the functional mechanism of IL-4 was clarified under clonal level. Materials and methodsCulture media and tumour cell lines Recombinant human IL-2 (Shionogi Pharmaceutical Co., Japan) and recombinant human ...

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“…The presence in breast tumors of considerable numbers of tumorassociated macrophages and tumor-infiltrating lymphocytes secreting a wide spectra of cytokines also suggests a key role for these factors in neoplastic cell activity (Kelly et al 1988, Whitford et al 1990). Moreover, it has been observed that Natural Killer cells isolated directly from ductal invasive breast tumors secrete important amounts of interferonand interleukin (IL)-4 (Tamm et al 1989).…”

Section: Local Control Of Estrogen and Androgen Formation And Inactivmentioning

confidence: 99%

Intracrinology: role of the family of 17 beta-hydroxysteroid dehydrogenases in human physiology and disease

Labrie¹,

Luu‐The²,

Lin³

et al. 2000

Journal of Molecular Endocrinology

259

166

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In women and men, an important proportion of estrogens and androgens are synthesized locally at their site of action in peripheral target tissues. This new field of endocrinology has been called intracrinology. In postmenopausal women, 100% of active sex steroids are synthesized in peripheral target tissues from inactive steroid precursors while, in adult men, approximately 50% of androgens are made locally in intracrine target tissues. The last and key step in the formation of all estrogens and androgens is catalyzed by members of the family of 17 -hydroxysteroid dehydrogenases (17 -HSDs) while different 17 -HSDs inactivate these steroids in the same cell where synthesis takes place. To date, seven human 17 -HSDs have been cloned, sequenced and characterized. The 17 -HSDs provide each cell with the means of precisely controlling the intracellular concentration of each sex steroid according to local needs.

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Flow cytometric analysis of tumour infiltrating lymphocytes in breast cancer

Cited by 81 publications

References 29 publications

Human Activated T Lymphocytes Modulate IDO Expression in Tumors through Th1/Th2 Balance

Human Activated T Lymphocytes Modulate IDO Expression in Tumors through Th1/Th2 Balance

Clonal and functional analysis for the augmentation of tumour-infiltrating lymphocytes by interleukin 4

Intracrinology: role of the family of 17 beta-hydroxysteroid dehydrogenases in human physiology and disease

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