Alterations in expression and function of signal transducing proteins in tumor-associated T and natural killer cells in ovarian carcinoma

Lai, P.; Rabinowich, Hannah; Crowley-Nowick, Peggy A.; Bell, Maria C.; Mantovani, Giovanni; Whiteside, Theresa L.

doi:10.1042/bst025218s

Cited by 115 publications

(144 citation statements)

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“…PBL (5 × 10 6 cells) from 5 normal volunteers were incubated with the partially purified zeta suppressor factor (10 ng ml -1 ) for 96 hours. Purified T cells were isolated by magnetic selection, as previously described (Lai et al, 1996). The resulting T-cells, which were >98% CD3+ cells, were isolated and lysed.…”

Section: Confirmation Of Cd3-zeta Suppression In Normal Lymphocytesmentioning

confidence: 99%

“…Functional abnormalities in T lymphocytes have been observed in patients with ovarian, cervical, renal cell, colorectal, prostate and head and neck cancers, including defective Ca 2+ mobilization, impaired tyrosine kinase activity, and decreased expression of TcR-associated zeta and epsilon chains (Tartour et al, 1995;Lai et al, 1996;Rabinowich et al, 1996;Mulder et al, 1997;deGruijl et al, 1999;Kuss et al, 1999). In patients with gynaecologic malignancies, the diminished expression of the signal-transducing zeta chain has been observed in both tumour-infiltrating T cells and peripheral blood lymphocytes of patients with advancedcancer (Lai et al, 1996;Rabinowich et al, 1996;deGruijl et al, 1999).…”

mentioning

confidence: 99%

“…In patients with gynaecologic malignancies, the diminished expression of the signal-transducing zeta chain has been observed in both tumour-infiltrating T cells and peripheral blood lymphocytes of patients with advancedcancer (Lai et al, 1996;Rabinowich et al, 1996;deGruijl et al, 1999). Decreased expression of CD3-zeta has been correlated with reduced proliferative responses following antigenic challenge and reduced cytokine production.…”

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confidence: 99%

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Modulation of TcR/CD3-zeta chain expression by a circulating factor derived from ovarian cancer patients

et al. 2001

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SummaryIn women with ovarian cancer, suppression of components of the immune system may promote tumour development. Previous studies in ovarian cancer have demonstrated that decreased expression and function of the T-cell receptor (TcR)-associated signal transducing zeta-chain correlates with deficient immune responsiveness of T cells. In this study, sera and ascitic fluids obtained from woman with advanced ovarian cancer were found to suppress the expression of TcR-associated zeta chain. This suppression of zeta chain expression was dose-dependent and was not observed with biologic fluids obtained from healthy women.The factor responsible for the loss of zeta chain was purified from ascites and characterized as a protein with an appropriate molecular weight of 14 kD. Suppression of T-cell TcR-zeta was specific, since neither lck nor ZAP-70 expression was affected, while zeta chain was almost completely suppressed. This selective suppression of TcR-zeta expression by the 14 kD ascites-derived factor was shown to operate at the mRNA level. By defining the mechanism through which this protein modulates TcR-zeta chain levels, it might be possible to ultimately prevent the suppressive influences of the tumour microenvironment and restor immune competence in patients with ovarian carcinoma.

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Section: Confirmation Of Cd3-zeta Suppression In Normal Lymphocytesmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Modulation of TcR/CD3-zeta chain expression by a circulating factor derived from ovarian cancer patients

et al. 2001

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“…To select for PBL, monocytes were removed on nylon wool columns (Lai et al, 1996). T cells were isolated from PBL by negative selection, using immunomagnetic beads as previously described (Lai et al, 1996). Two-color¯ow cytometry was used to con®rm the purity of negatively-selected T cell populations.…”

Section: Cell Lines and Cellsmentioning

confidence: 99%

Interleukin-2 expression in human carcinoma cell lines and its role in cell cycle progression

et al. 2000

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“…1. NK cells isolated from the ascites of ovarian carcinoma patients expressed decreased levels of the adaptor proteins CD3ζ and FcεRIγ and Lck kinase compared to NK cells from peripheral blood [89]. These features correlated with their reduced ability to produce IFN-γ upon IL-2 stimulation.…”

Section: Shaping Of Nk Cell Function By the Tumor Microenvironmentmentioning

confidence: 93%

Shaping of NK Cell Responses by the Tumor Microenvironment

Stojanović

Correia

Cerwenka

2012

Cancer Microenvironment

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Natural killer (NK) cells belong to the innate immune system and are potent cytolytic and cytokineproducing effector cells in response to tumor targets. NK cell based anti-tumor immunotherapy was so far mainly successful in patients with different types of leukemia. For instance, acute myeloid leukemia (AML) patients displayed a prolonged survival if transplanted with haploidentical stem cells giving rise to NK cells with a mismatch in inhibitory killer immunoglobulin receptors (KIRs) and recipients' HLA class I. Although promising results have been achieved with hematological tumors, solid tumors are in most cases poorly controlled by NK cells. Therapeutic protocols that aimed at improving NK cell responses in patients with solid malignancies succeeded in increasing NK cell numbers and functional responses of NK cells isolated from the patients' peripheral blood. However, in the majority of cases tumor progression and overall survival of patients were not significantly improved. There is increasing evidence that tumor-associated NK cells become gradually impaired during tumor progression compared to NK cells from peripheral blood and healthy tissues. Future protocols of NK cell based immunotherapy should integrate three important aspects to improve NK cell anti-tumor activity: facilitating NK cell migration to the tumor site, enhancing their infiltration into the tumor tissue and ensuring subsequent efficient activation in the tumor. This review summarizes the current knowledge of tumor-infiltrating NK cells and the influence of the tumor microenvironment on their phenotype and function.

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Alterations in expression and function of signal transducing proteins in tumor-associated T and natural killer cells in ovarian carcinoma

Cited by 115 publications

References 4 publications

Modulation of TcR/CD3-zeta chain expression by a circulating factor derived from ovarian cancer patients

Modulation of TcR/CD3-zeta chain expression by a circulating factor derived from ovarian cancer patients

Interleukin-2 expression in human carcinoma cell lines and its role in cell cycle progression

Shaping of NK Cell Responses by the Tumor Microenvironment

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