Downregulation of the proteasome subunits, transporter, and antigen presentation in hepatocellular carcinoma, and their restoration by interferon‐γ

Matsui, Masanao; Machida, Sanae; Itani-Yohda, Teru; Akatsuka, Toshitaka

doi:10.1046/j.1440-1746.2002.02837.x

Cited by 69 publications

(57 citation statements)

References 56 publications

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“…Primary reasons for this can be in the immune system itself such as development of self tolerance in the thymus or in the periphery [23] . The tumor can also develop various evasion strategies like converting T helper cells or lowering the expression of tumor specific antigens to below the required threshold [24][25][26] . These mechanisms would lead to a low quantity of TIL.…”

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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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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“…These results suggest that stored FasL and newly synthesized FasL are used in distinct biological contexts. Interference with Ag presentation is used by some viruses and tumors as an immune evasion strategy (35)(36)(37)(38). FasL from stored pools could contribute significantly to the antiviral, antitumor immunity when class I MHC expression or the presented viral/tumor Ag level is reduced.…”

Section: Discussionmentioning

confidence: 99%

Stored Fas Ligand, a Mediator of Rapid CTL-Mediated Killing, Has a Lower Threshold for Response Than Degranulation or Newly Synthesized Fas Ligand

Gong

Ostergaard

2009

The Journal of Immunology

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CTL lyse target cells through the release of cytolytic granule mediators and expression of the death receptor ligand Fas ligand (FasL). We previously demonstrated that FasL is stored in vesicles distinct from cytolytic granules and is translocated to the cell surface within 15 min of TCR stimulation, followed by a later wave of newly synthesized FasL cell surface expression at 2 h poststimulation. Initial studies suggested that the two FasL responses had different signaling thresholds. To test this possibility directly, we titrated Ag presented to murine CTL to measure FasL and degranulation response thresholds. Stored FasL translocation to the cell surface required substantially lower concentrations of peptide than was required for de novo expression of FasL and degranulation. Furthermore, a low-affinity agonist peptide stimulated strong stored FasL translocation but only limited de novo FasL expression and degranulation. These data imply that the two FasL populations may have distinct functions. We examined bystander killing and found that the rapidly expressed FasL triggered highly specific lysis of target cells, as did degranulation. In contrast, the newly synthesized later wave of FasL mediated extensive Fas-dependent bystander killing. Our data indicate that stored FasL is mobilized in response to low concentrations of Ag to mediate rapid, highly specific lysis of target cells, whereas the later, newly synthesized FasL requires higher concentrations of Ag and mediates indiscriminate lysis. These findings suggest that early and late FasL and degranulation represent nonredundant lytic mechanisms that have been selected for distinct situations, possibly for optimal pathogen clearance.

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“…Failed HCCassociated antigen presentation by DCs might not only be due to a decreased expression of human leukocyte antigen (HLA) classⅠ molecules [11] , as maturation defects like reduced endocytosis, allostimulation, and interleukin 12 (IL12) secretion can lead to a weak T cell immune response [12] . Even in the presence of strong maturation stimuli like high levels of inflammatory cytokines, DCs remain refractory to these stimulatory signals.…”

Section: Dendritic Cellsmentioning

confidence: 99%

“…Factors promoting tumor antigen tolerance, such as decreased recognition of malignant cells, suppression of immunity, and chronic inflammation (either mediated by virus [8] or immune dysregulation), all lead to carcino genesis [9] . Recent studies have provided evidence that a dysregulated immune system, including changes in the number or function of immune cells, cytokine levels, and expression of inhibitory receptors or their ligands significantly contribute to the development of HCC [10,11] . Alterations in the function or expression of immune components shift the immune response towards tumor tolerance, resulting in its progression.…”

Section: Introductionmentioning

confidence: 99%

Immunology of hepatocellular carcinoma

Sachdeva

Chawla

Arora

2015

WJH

100

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Hepatocellular carcinoma (HCC) is primarily a malignancy of the liver, advancing from a damaged, cirrhotic liver to HCC. Globally, HCC is the sixth most prevalent cancer and the third-most prevalent reason for neoplastic disease-related deaths. A diverse array of infiltrating immunocytes regulates the development and progression of HCC, as is the case in many other cancers. An understanding of the various immune components during HCC becomes necessary so that novel therapeutic strategies can be designed to combat the disease. A dysregulated immune system (including changes in the number and/or function of immune cells, cytokine levels, and the expression of inhibitory receptors or their ligands) plays a key role in the development of HCC. Alterations in either the innate or adaptive arm of the immune system and cross-talk between them make the immune system tolerant to tumors, leading to disease progression. In this review, we have discussed the status and roles of various immune effector cells (e.g. , dendritic cells, natural killer cells, macrophages, and T cells), their cytokine profile, and the chemokine-receptor axis in promoting or impeding HCC.

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Downregulation of the proteasome subunits, transporter, and antigen presentation in hepatocellular carcinoma, and their restoration by interferon‐γ

Cited by 69 publications

References 56 publications

Liver tumor infiltrating lymphocytes: Comparison of hepatocellular and cholangiolar carcinoma

Liver tumor infiltrating lymphocytes: Comparison of hepatocellular and cholangiolar carcinoma

Stored Fas Ligand, a Mediator of Rapid CTL-Mediated Killing, Has a Lower Threshold for Response Than Degranulation or Newly Synthesized Fas Ligand

Immunology of hepatocellular carcinoma

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