Dendritic cells, T-cell infiltration, and grp94 expression in cholangiocellular carcinoma

Takagi, Satoshi; Miyagawa, Shinichi; Ichikawa, Eri; Soeda, Junpei; Miwa, Shiro; Miyagawa, Yusuke; Iijima, Satoshi; Noike, Terumasa; Kobayashi, Adam; Kawasaki, Seiji

doi:10.1016/j.humpath.2004.03.016

Cited by 69 publications

(57 citation statements)

References 32 publications

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“…Takagi and coworkers found that patients with high numbers of TIL (CD8+ or CD4+) had significantly better prognosis [30] . In our study, the amount of TILs was heterogeneous.…”

Section: Discussionmentioning

confidence: 99%

Liver tumor infiltrating lymphocytes: Comparison of hepatocellular and cholangiolar carcinoma

Kasper¹,

Drebber²,

Stippel³

et al. 2009

WJG

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AIM:To investigate the role of tumor infiltrating lymphocytes (TIL) in primary hepatocellular and cholangiolar carcinomas of the liver. METHODS:Immunohistochemical analysis was performed including antibodies to CD3, CD4, CD8, CD20, CD56 and TIA-1 in formalin-fixed and paraffin-embedded tissue of 35 liver resection specimens of hepatocellular or cholangiocellular carcinomas. Semiquantitative evaluation was performed with emphasis on the area of the tumor itself and of the tumor/liver interface. RESULTS:All hepatocellular carcinomas showed infiltration of lymphocytes predominantly around the tumor in the tumor/liver interface consisting mainly of CD3+ CD4+ T lymphocytes [164.3/10 high power fields (HPF)] and in the tumor itself of CD8+ cells (54.9/10 HPF). Cholangiocarcinomas contained a heterogeneous amount of TIL, composed mainly of CD3+ T cells with a predominance of CD8+ cells in the tumor tissue (52.6/10 HPF) and of CD4+ cells in the interface region (223.1/10 HPF). CD56+ cells of the innate immune system were scarce. There was no significant difference between hepatocellular or cholangiolar carcinoma. No correlation with the clinicopathological data was seen. CONCLUSION:Liver TIL consists of intratumoral CD8+ T cells and peritumoral CD4+ T cells independent of histogenetic origin. Different functions of lymphocytes in these regions seem possible.

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“…Takagi and coworkers found that patients with high numbers of TIL (CD8+ or CD4+) had significantly better prognosis [30] . In our study, the amount of TILs was heterogeneous.…”

Section: Discussionmentioning

confidence: 99%

Liver tumor infiltrating lymphocytes: Comparison of hepatocellular and cholangiolar carcinoma

Kasper¹,

Drebber²,

Stippel³

et al. 2009

WJG

View full text Add to dashboard Cite

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“…The infiltration of primary tumors with different subsets of DCs was evaluated in studies about colorectal cancer [5][6][7], gastric cancer [8,9], and in primary hepatic tumors [10][11][12]. In these studies high numbers of CD83-positive and HLA-DR-positive DCs in tumor tissue were linked to a better prognosis, reduced tumor recurrence, and fewer metastases.…”

Section: Introductionmentioning

confidence: 99%

Recruitment of dendritic cells in human liver with metastases

Gulubova

Manolova

Cirovski

et al. 2008

Clin Exp Metastasis

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Dendritic cells (DCs) play a key role in the generation of antitumor immune responses as the most potent professional antigen-presenting cells. In this study we examined the distribution of DCs subsets in selected areas of liver metastases and adjacent liver tissue of 74 patients with gastrointestinal cancers (14 gastric, 47 colon, and 13 rectal) using immunohistochemistry for the DCs markers S-100 protein, HLA-DR, CD1a, and CD83. S-100 protein-positive DCs were localized mainly in clusters in metastases and at the tumor border with the surrounding liver tissue, while HLA-DR-positive DCs were significantly more in number (P<0.0001) and were diffusely distributed in metastasis stroma and at the tumor border. S-100 protein-positive DCs with mature phenotype were presented around metastases and in the sinusoidal lumena, whereas S-100 protein-positive DCs with less mature phenotype based on their ultrastructure were scattered in the tumor stroma. CD1a- and CD83-positive DCs were observed predominantly in small groups or as single cells in the tumor stroma and in the invasive margin. The numbers of CD1a-positive DCs (immature) and CD83-positive DCs (mature) were comparable, but significantly lower than that of S-100 protein-positive (P<0.0001) and HLA-DR-positive cells (P<0.0001).We observed more S-100 protein-positive DCs and HLA-DR-expressing cells in the sinusoids and portal tracts of the liver tissue, surrounding metastases, than in control liver tissue. In conclusion, this study provides additional information on the functional subtypes and distribution of DCs infiltrating metastatic tissue and local liver environment in patients with liver metastases from gastrointestinal cancers.

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“…Indirect evidence suggests that T cell immunity may participate in controlling disease progression for GI adenocarcinomas arising in the esophagus, stomach, pancreas, liver, bile ducts, gallbladder, colon, and rectum (10)(11)(12)(13)(14)(15)(16)(17)(18). A redefinition of prognostic staging is being proposed based on the density of the TILs found in primary tumors, among which colorectal cancer has been studied most extensively (19).…”

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confidence: 99%

Phenotype and Function of T Cells Infiltrating Visceral Metastases from Gastrointestinal Cancers and Melanoma: Implications for Adoptive Cell Transfer Therapy

Turcotte

Gros

Hogan

et al. 2013

The Journal of Immunology

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Adoptive cell transfer of tumor-infiltrating lymphocytes (TILs) can mediate cancer regression in patients with metastatic melanoma, but whether this approach can be applied to common epithelial malignancies remains unclear. In this study, we compared the phenotype and function of TILs derived from liver and lung metastases from patients with gastrointestinal (GI) cancers (n = 14) or melanoma (n = 42). Fewer CD3+ T cells were found to infiltrate GI compared with melanoma metastases, but the proportions of CD8+ cells, T cell differentiation stage, and expression of costimulatory molecules were similar for both tumor types. Clinical-scale expansion up to ∼50 × 109 T cells on average was obtained for all patients with GI cancer and melanoma. From GI tumors, however, TIL outgrowth in high-dose IL-2 yielded 22 ± 1.4% CD3+CD8+ cells compared with 63 ± 2.4% from melanoma (p < 0.001). IFN-γ ELISA demonstrated MHC class I–mediated reactivity of TIL against autologous tumor in 5 of 7 GI cancer patients tested (9% of 188 distinct TIL cultures) and in 9 of 10 melanoma patients (43% of 246 distinct TIL cultures). In these assays, MHC class I–mediated up-regulation of CD137 (4-1BB) expression on CD8+ cells suggested that 0–3% of TILs expanded from GI cancer metastases were tumor-reactive. This study implies that the main challenge to the development of TIL adoptive cell transfer for metastatic GI cancers may not be the in vitro expansion of bulk TILs, but the ability to select and enrich for tumor-reactive T cells.

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Dendritic cells, T-cell infiltration, and grp94 expression in cholangiocellular carcinoma

Cited by 69 publications

References 32 publications

Liver tumor infiltrating lymphocytes: Comparison of hepatocellular and cholangiolar carcinoma

Liver tumor infiltrating lymphocytes: Comparison of hepatocellular and cholangiolar carcinoma

Recruitment of dendritic cells in human liver with metastases

Phenotype and Function of T Cells Infiltrating Visceral Metastases from Gastrointestinal Cancers and Melanoma: Implications for Adoptive Cell Transfer Therapy

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