Immune Cells in the Tumor Microenvironment

Whiteside, Theresa L.

doi:10.1002/3527600795.ch6

Cited by 4 publications

(2 citation statements)

References 56 publications

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“…Tumours can disrupt immune cell function through a variety of mechanisms [36]. Indeed, solid tumours have been shown to be capable of inducing apoptosis in T cells either through cell–cell contact via Fas ligand (FasL) [26–28] or through secretion of factors such as soluble FasL [39]. However, propidium iodide staining of nuclei from lymphocytes exposed to HL60 supernatant showed no evidence of apoptosis, suggesting that the immunosuppressive factor(s) in question blocked proliferation by simply arresting cell division.…”

Section: Discussionmentioning

confidence: 99%

Acute myeloid leukaemia cells secrete a soluble factor that inhibits T and NK cell proliferation but not cytolytic function – implications for the adoptive immunotherapy of leukaemia

Orleans-Lindsay

Barber

Prentice

et al. 2001

Clinical and Experimental Immunology

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SUMMARYEvidence of an immune mediated graft-versus-leukaemia effect has led to the belief that T and NK cell based adoptive immunotherapy can constitute effective treatment for relapsed leukaemias. However, work on solid tumours has shown this strategy may be hampered, by an immune escape mechanism in which tumour secreted immunosuppressive factors compromise T and NK cell function. Indeed, acute myeloid leukaemia (AML) cells secrete immunosuppressive factors that block the synthesis of Th1 type cytokines in T cells. We demonstrate here that this immunosuppression, mediated by both HL60 AML cell line and primary AML blasts, inhibits T and NK cell proliferation but not cytolytic activity. Supernatants from HL60 cell line and primary AML blasts inhibited T cell proliferation to mitogenic and alloantigen stimulation but had no effect on cytolytic function. Similarly, the proliferation of NK cells to IL-2 and IL-15 stimulation was inhibited whilst their cytolytic function, shown by lysis of AML blasts, K562 and Daudi cells remained unaffected. The failure of T and NK cells to proliferate was not due to effector cell apoptosis. Indeed, removal of lymphocytes from the immunosuppressive environment partially restored their capacity to respond to mitogenic stimulation. T cells exposed to immunosuppressive supernatants did not increase expression of mitotic inhibitory proteins that arrest cell division, thereby ruling this out as a mechanism of operation for this immunosuppression. T cell expansion requires antigen stimulation, usually provided in the form of AML blasts, therefore our data suggest that NK cells may be more practical for the immunotherapy of AML.

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Section: Discussionmentioning

confidence: 99%

Acute myeloid leukaemia cells secrete a soluble factor that inhibits T and NK cell proliferation but not cytolytic function – implications for the adoptive immunotherapy of leukaemia

Orleans-Lindsay

Barber

Prentice

et al. 2001

Clinical and Experimental Immunology

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“…Tumours are often infiltrated with various lymphocytes including NK cells, macrophages, DCs, T cells and B cells . Notch signalling has recently been implicated in the development and functioning of these immune cells.…”

Section: Notch Mediated Immune Surveillance Through Lymphocytesmentioning

confidence: 99%

Dichotomy of Notch signalling in regulating tumour immune surveillance

2019

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Notch signalling is an evolutionarily conserved multifaceted pathway that controls diverse cellular processes. Its role in regulating development and tissue homeostasis is well established. Aberrant activation of the Notch pathway has been implicated in the initiation and progression of many types of cancers. However, although in some cancers Notch signalling acts as a tumour-promoter, in others it is reported to suppress tumour growth and progression. Accumulating evidence suggests the involvement of both the innate and adaptive immune system in the development of various tumours. Currently, extensive studies on investigating the effects of Notch signalling in tumour immune surveillance are being carried out.Interestingly, recent literature shows how the changing expression of Notch genes in different T cell subsets like CD4 and CD8 helps in controlling anti-tumour immune responses. In this review, we discuss in depth the roles of Notch signalling molecules and different immune cells in the context of the tumour microenvironment. We also outline how current knowledge can be exploited to develop novel therapies in order to control the propagation of cancer stem cells.

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