Impaired function of circulating dendritic cells in patients with pancreatic cancer

Yanagimoto, Hiroaki; Takai, Soichiro; Satoi, Sohei; Toyokawa, Hideyoshi; Takahashi, Kanji; Terakawa, N.; Kwon, A‐Hon; Kamiyama, Yasuo

doi:10.1016/j.clim.2004.09.007

Cited by 78 publications

(67 citation statements)

References 33 publications

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“…Recently it has been suggested that chemotherapy might improve the immune function by reducing the levels of immunosuppressive cytokines produced by cancer cells (81). In comparison with the pre-treatment conditions, we found no significant changes in LPS-induced IL-12 total p40 and p70 by PBMC, nor in anti-CD3-induced IFN-Á release by T cells.…”

Section: ------------------------------------------------------------contrasting

confidence: 43%

Impact of surgery and chemotherapy on cellular immunity in pancreatic carcinoma patients in view of an integration of standard cancer treatment with immunotherapy

Bellone¹

2009

Int J Oncol

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Abstract.As surgery and chemotherapy may act as adjuvants providing antitumor immunity benefits, we ran phenotypical and functional immunomonitoring in patients with resectable pancreatic adenocarcinoma and advanced metastatic disease receiving combined treatment (cisplatin, gemcitabine, 5-FU). Blood was taken before/one month after resection; before/ during chemotherapy. Controls were age-and gender-matched. Circulating lymphocyte, myeloid and plasmacytoid dendritic cell (MDC and PDC) subsets were examined by flow cytometry; functional activity by mixed lymphocyte reaction (MLR) for DC allostimulation, through 4-h 51 Cr-release assay for Natural Killer (NK) and lymphokine-activated-killer (LAK) cell cytotoxicity; ELISA for spontaneous/activated cytokine release by PBMC and T cells. Significant differences occurred in several parameters between pretreatment patient and control values: fewer CD8 + cells and increased apoptosisprone CD3 + /CD95 + lymphocytes, higher frequency of MDC, reduced allostimulatory activity by ex vivo-generated DC, depressed LAK activity, elevated IL-10 and IL-12p40 production; impaired IL-12p70 and IFN-Á production by stimulated PBMC and T cells. Only IL-12p70 level was correlated with survival. One month after radical, but not palliative surgery, the percentage of T-lymphocytes coexpressing CD3/CD95 decreased significantly, the stimulatory capacity of DC increased, and LPS-induced IL12p70 release by PBMC rose concomitantly with the anti-CD3 stimulated-IFN-Á production by T cells. In patients with locally advanced or metastatic disease, one and/or two combined drug cycles increased percentage of CD4 + cells and LAK cell cytotoxicity and decreased PDC frequency and spontaneous/LPS-stimulated IL-10 by PBMC. Results suggest immunological changes induced by surgical resection/ combined chemotherapy indicate specific precisely-timed windows of opportunity for introducing immunotherapy in pancreatic cancer, possibly improving survival in this highly lethal disease.

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Section: ------------------------------------------------------------contrasting

confidence: 43%

Impact of surgery and chemotherapy on cellular immunity in pancreatic carcinoma patients in view of an integration of standard cancer treatment with immunotherapy

Bellone¹

2009

Int J Oncol

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“…CD40 and CD40L modulate the anti-tumor immunity by influencing the development, activation, proliferation and differentiation of a series of immune cells (27). Unfortunately, the mechanism by which CD40-CD40L regulates immune functions is not fully known.…”

Section: Discussionmentioning

confidence: 99%

“…However, the mechanism on how CD40 was involved in the process remained to be further investigated. Recent data showed that down-regulation of CD40 on DC cell surface and low-level CD40L on T cell surface of patients with pancreatic cancer impaired the function of DC cells, which was closely associated with the immunosuppressive status of cancer patients (26,27). Therefore, CD40 may be a valuable marker to predict the malignancy, invasive and metastatic potential and prognosis in pancreatic cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Expression of the co-signaling molecules CD40-CD40L and their growth inhibitory effect on pancreatic cancer in vitro

Zhao

Fei

et al. 2012

Oncol Rep

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Abstract. We investigated the expression of the co-signalling molecule CD40 in pancreatic cancer and the growth inhibitory effect of the recombinant soluble human CD40 ligand (rshCD40L) in pancreatic cancer cell lines. Twenty-six cases of pancreatic cancer tissues and corresponding paratumoral normal tissues were immunohistochemically analyzed for CD40 expression. The association of CD40 expression with clinicopathological parameters, including clinical stage, pathological grade, invasion and metastasis, were statistically analyzed. The serum sCD40 levels in pancreatic cancer patients were examined by ELISA. The expression of CD40 in the pancreatic cancer cell lines Panc-1, Aspc-1 and Miapaca-2 was examined by RT-PCR and flow cytometry. The growth inhibitory activity of rshCD40L on pancreatic cancer cell lines was determined by MTT assay. Tumor cell apoptosis was detected by TUNEL and Annexin V/ PI double staining method. CD40 was positive both on the membrane and in the cytoplasm of tumor cells, 69.2% (18/26) of the cases were positive for CD40. CD40 expression was significantly higher in pancreatic cancer tissues compared to adjacent normal tissues (P<0.05). High CD40 expression was associated with TNM stage and lymph node metastasis (both P<0.05). Patients with pancreatic cancer have higher serum sCD40L levels (3.53±0.70 ng/ml) compared to healthy subjects (1.81±0.48 ng/ml, P<0.05). rshCD40L significantly inhibited the proliferation of the pancreatic cancer cell lines and induced apoptosis in these cell lines. The co-signaling molecule CD40 is highly expressed in pancreatic cancer tissues and cell lines and rshCD40L is a potential tool for antitumor therapies.

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“…A decrease in the proportion of circulating myeloid DC (mDC) has been observed in patients with head and neck squamous cell carcinoma (16), and in patients with locally advanced pancreatic cancer the population of circulating mDC1 was not only found to be reduced in size but also reduced in T cell allostimulatory activity and in the capacity to produce IL-12p70 (17). There is considerable evidence that iNKT-DC interactions help initiate and regulate immune responses (18 -20).…”

Section: T He Cd1d-restricted Invariant Nkt (Inkt)mentioning

confidence: 99%

Circulating Myeloid Dendritic Cells of Advanced Cancer Patients Result in Reduced Activation and a Biased Cytokine Profile in Invariant NKT Cells

Vliet

Wang

Yue

et al. 2008

The Journal of Immunology

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CD1d-restricted invariant NKT (iNKT) cells play important regulatory roles in various immune responses, including antitumor immune responses. Previous studies have demonstrated quantitative and qualitative defects in iNKT cells of cancer patients, and these defects are clinically relevant as they are associated with poor prognosis. In this study we demonstrate that defects in the iNKT cell population can, at least in part, be attributed to defective interactions between iNKT cells and CD1d-expressing circulating myeloid dendritic cells (mDC), as mDC of patients with advanced melanoma and renal cell cancer reduced the activation and Th1 cytokine production of healthy donor-derived iNKT cells. Interestingly, this reduced activation of iNKT cells was restricted to patients with low circulating iNKT cell numbers and could be reversed by IL-12 and in part by the neutralization of TGF-β, but it was further reduced by the neutralization of IL-10 in vitro. Additional experiments revealed discordant roles for TGF-β and IL-10 on human iNKT cells, because TGF-β suppressed iNKT cell activation and proliferation and IFN-γ production while IL-10 was identified as a cytokine involved in stimulating the activation and expansion of iNKT cells that could subsequently suppress NK cell and T cell responses.

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Impaired function of circulating dendritic cells in patients with pancreatic cancer

Cited by 78 publications

References 33 publications

Impact of surgery and chemotherapy on cellular immunity in pancreatic carcinoma patients in view of an integration of standard cancer treatment with immunotherapy

Impact of surgery and chemotherapy on cellular immunity in pancreatic carcinoma patients in view of an integration of standard cancer treatment with immunotherapy

Expression of the co-signaling molecules CD40-CD40L and their growth inhibitory effect on pancreatic cancer in vitro

Circulating Myeloid Dendritic Cells of Advanced Cancer Patients Result in Reduced Activation and a Biased Cytokine Profile in Invariant NKT Cells

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