The ‘kiss of death’ by dendritic cells to cancer cells

Chan, Chun Man; Housseau, Franck

doi:10.1038/sj.cdd.4402235

Cited by 64 publications

(51 citation statements)

References 89 publications

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“…The first pathway is granule exocytosis, which delivers a membrane-disrupting molecule perforin (pore-forming protein) and proapoptotic serine proteases Gzms. The second one is involved in death receptor-induced surface expression of ligands on killer cells, which cross-links the corresponding receptors of target cells such as Fas ligand and TRAIL and TNFR (16). In our study, we found that the cytotoxic granules exocytosis inhibitor CMA can block NK-induced tumor lysis.…”

Section: Discussionmentioning

confidence: 54%

Ignition of p53 Bomb Sensitizes Tumor Cells to Granzyme K-Mediated Cytolysis

Hua

Wang

Zhong

et al. 2009

The Journal of Immunology

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Inactivation of tumor suppressor p53 results in loss of the apoptosis-regulating function of the p53 protein in tumor cells. Restoration of wild-type p53 expression in p53 mutant tumor cells increases tumor susceptibility to CTL-mediated cytolysis. However, the direct role of p53 in regulating tumor sensitivity to NK cell-mediated lysis and the functional relationship between p53 and granzymes in the control of tumor killing are still poorly documented. In this study, we found that p53 can sensitize tumor-killing susceptibility to NK and granzyme K-mediated cytolysis. Granzyme K is constitutively expressed in high levels in NK cells and induces rapid caspase-independent cell death. Granzyme K may exert a critical role in NK cell-mediated tumor clearance. p53 associates with granzyme K and is a physiological substrate of granzyme K. p53 was processed to three cleavage products of p40, p35, and p13 fragments at Lys24 and Lys305. These three cleavage products harbor strong proapoptotic activities that amplify the proapoptotic action of p53 to potentiate tumor-killing sensitivity. Therefore, p53 is as a cytotoxic bomb that can be triggered by granzyme K, leading to potentiating killing efficacy.

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Section: Discussionmentioning

confidence: 54%

Ignition of p53 Bomb Sensitizes Tumor Cells to Granzyme K-Mediated Cytolysis

Hua

Wang

Zhong

et al. 2009

The Journal of Immunology

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“…One area of focus should be on age-related changes associated with tumour-antigen capture and presentation. In brief, dendritic cells capture and process tumour-specific antigens, they begin to mature and migrate to the lymph nodes where they interact with cytotoxic T-lymphocytes (CTLs), presenting the tumour information and causing the CTLs to become activated and proliferate, targeting tumour cell removal (Chan and Housseau 2008). If senescent cells are indeed removed by the immune system, the mechanism is probably similar to that of tumour cell removal.…”

Section: Future Considerationsmentioning

confidence: 99%

Cellular senescence, ageing and disease

Burton

2008

AGE

116

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Cellular senescence is the irreversible growth arrest of individual mitotic cells, which as a consequence display a radically altered phenotype that is thought to impair tissue function and predispose tissues to disease development and/or progression as they gradually accumulate. However, in the past, research into mechanisms of ageing has commonly been researched and treated separately from disease development. This may partly be due to the lack of understanding concerning mechanisms of ageing and the difficulty in implementing what was known into models of disease development. Only in the last 10 years, with increasing knowledge of the senescent phenotype and the ability to detect senescent cells in human tissues, have biologists been able to investigate the relationship between cellular senescence and disease. This review therefore brings together and discusses recent findings which suggest that cellular senescence does contribute to ageing and the development/ progression of disease.

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“…11 However, the DC maturation capacity is altered in tumor-bearing hosts and DC subsets in tumors are predominantly immature/nonactivated cells that mediate tolerance to the tumor by inducing Tcell anergy and regulatory T cells. 5,[12][13][14][15] The failure of immune cells in the tumor microenvironment to mount an effective immune response and their promotion of tumor progression instead may be rooted in a constitutive activation of signal transducer and activator of transcription 3 (STAT3) in both tumor cells and immune cells. STAT3 is a point of convergence for numerous oncogenic signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

Intratumoral neutrophils and plasmacytoid dendritic cells indicate poor prognosis and are associated with pSTAT3 expression in AJCC stage I/II melanoma

Jensen

Schmidt

Møller

et al. 2011

Cancer

220

174

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BACKGROUND: Tumor cell and host immune cell interaction plays a key role in carcinogenesis. Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in cancer and believed to be an important mediator of tumor-induced immunosuppression. This paper aims to describe the prognostic impact of neutrophil and dendritic cell infiltration in primary melanoma and the association of this infiltration with activated STAT3 (pSTAT3) in primary melanoma cells. METHODS: Formalin-fixed, paraffin-embedded primary melanomas from 186 stage-I/II melanoma patients surgically resected from 1997 to 2000. Infiltrating neutrophils (CD66b), dendritic cells (CD123þ and DC-LAMPþ), T-lymphocytes (CD8) and pSTAT3 melanoma cell expression were studied by immunohistochemistry and evaluated as present or absent. DC-LAMPþ cell infiltration was evaluated as absent/few versus dense. Study endpoints: relapse-free survival, melanoma-specific, and overall survival. RESULTS: The median observation time was 12.2 years (range, 10.4-14.2 years). Fifty-one deaths were observed of which 38 (20%) were melanoma-specific. In a multivariate Cox proportional hazards model including ulceration and melanoma thickness, neutrophil and CD123þ dendritic cell infiltration were independently associated with poor prognosis (CD66b: hazard ratio [HR] ¼ 3.13; 95% confidence interval [CI], 1.43-6.83; P ¼ .004; CD123: HR ¼ 2.45; 95% CI, 1.22-4.92; P ¼ .012). The association between melanoma cell pSTAT3 expression and immune infiltration (neutrophils and CD123þ cells) was strong. pSTAT3 expression, CD8 and DC-LAMP infiltration were not independently associated with poor prognosis. CONCLUSIONS: Neutrophil infiltration and CD123þ dendritic cell infiltration in primary melanoma are independently associated with poor prognosis. Melanoma cell expression of pSTAT3 is strongly associated with the surrounding immune infiltrate. Cancer 2012;118:2476-

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The ‘kiss of death’ by dendritic cells to cancer cells

Cited by 64 publications

References 89 publications

Ignition of p53 Bomb Sensitizes Tumor Cells to Granzyme K-Mediated Cytolysis

Ignition of p53 Bomb Sensitizes Tumor Cells to Granzyme K-Mediated Cytolysis

Cellular senescence, ageing and disease

Intratumoral neutrophils and plasmacytoid dendritic cells indicate poor prognosis and are associated with pSTAT3 expression in AJCC stage I/II melanoma

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