MHC class I antigens and tumour-infiltrating leucocytes in laryngeal cancer: long-term follow-up

Esteban, Francisco; Redondo, Maximino; Delgado, María del Pilar Núñez; Garrido, Federico; Ruiz‐Cabello, Francisco

doi:10.1038/bjc.1996.633

Cited by 22 publications

(13 citation statements)

References 35 publications

(13 reference statements)

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“…This frequency is similar to that found in 70 maxillary sinus SCC lesions (11), but is higher than that previously described in laryngeal SCC lesions, which range between 29% and 66% (6,(12)(13)(14)(15)(16). Our study differs from the other published Figure 4.…”

Section: Discussioncontrasting

confidence: 57%

“…Laryngeal SCC is no exception to this finding. The frequency of HLA class I antigen defects in laryngeal SCC lesions reported in the literature ranges between 29% and 66% (6,(12)(13)(14)(15)(16). Because of the role of HLA class I antigens in the presentation of tumor antigen (TA)-derived peptides to the host's immune system, these defects are likely to have a negative effect on the clinical course of the disease and on the outcome of T cell-based immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

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HLA Class I Antigen Down-regulation in Primary Laryngeal Squamous Cell Carcinoma Lesions as a Poor Prognostic Marker

Ogino¹,

Shigyo²,

Ishii³

et al. 2006

Cancer Research

164

124

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We have investigated the role of antigen-processing machinery (APM) component defects in HLA class I antigen downregulation in laryngeal squamous cell carcinoma (SCC) lesions and assessed the clinical significance of these defects. To this end, 63 formalin-fixed, paraffin-embedded tumor lesions were examined for APM component and HLA class I antigen expression by immunohistochemistry. Calnexin, calreticulin, and ERp57 were down-regulated in f25% of the lesions tested, whereas LMP2, TAP1, tapasin, and HLA class I antigens were down-regulated in at least 70% of the lesions tested. LMP2 and tapasin expression was significantly correlated with HLA class I antigen expression suggesting APM component defects as a mechanism underlying HLA class I antigen downregulation in laryngeal SCC lesions. The expression of most APM components and HLA class I antigens was correlated with the extent of CD8 + T cell infiltration into tumor lesions. Furthermore, LMP2 and HLA class I antigen down-regulation and low CD8 + T cell infiltration were significantly associated with reduced patients' survival. Multivariate analysis identified HLA class I antigen down-regulation as an independent unfavorable prognostic marker. This association is likely to reflect the reduction in the extent of CD8 + T cell infiltration in laryngeal SCC lesions. (Cancer Res 2006; 66(18): 9281-9)

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Section: Discussioncontrasting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

HLA Class I Antigen Down-regulation in Primary Laryngeal Squamous Cell Carcinoma Lesions as a Poor Prognostic Marker

Ogino¹,

Shigyo²,

Ishii³

et al. 2006

Cancer Research

164

124

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“…(3). Such an immune escape mechanism has also been suggested for HNSCC cells and might be reflected by a low T cell infiltration of tumors or by inefficient activation and generation of HNSCC-associated antigenspecific CTL as described by several investigators (20,22,25). Restoration of antigen presentation by cytokine treatment and/or gene transfer of deficient APM component consequently renders cells sensitive to CTL-mediated lysis.…”

Section: Discussionmentioning

confidence: 99%

“…In melanoma, breast, lung, and cervical carcinoma, the lack of HLA class I antigen surface expression and/or TAP expression was reported to be associated with poor tumor differentiation, increased frequency of aneuploidy as well as reduced survival rate (37,38,45,46). Conflicting information is available about the association between HLA class I antigen down-regulation and patients' survival in HNSCC patients (25,26,47). Our results are in accordance with those reported by one of the authors (26) showing a significant correlation between the survival time and a loss or down-regulation of APM components in primary maxillary sinus squamous cell carcinoma lesions.…”

Section: Discussionmentioning

confidence: 99%

Defects in the Human Leukocyte Antigen Class I Antigen Processing Machinery in Head and Neck Squamous Cell Carcinoma: Association with Clinical Outcome

Meißner

Reichert

Kunkel

et al. 2005

Clinical Cancer Research

225

180

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Purpose: Human leukocyte antigen (HLA) class I antigen defects, which are frequently present in head and neck squamous cell carcinoma (HNSCC) cells may provide the tumor with an escape mechanism from immune surveillance. Scanty information is available about mechanisms underlying HLA class I antigen defects in both lesions and cell lines from HNSCC. In this study, we investigate the role of antigen processing machinery (APM) component abnormalities in the generation of deficient HLA class I surface expression of HNSCC cells. Experimental Design: Using immunohistochemistry, Western blot, and RT-PCR analyses we correlated the expression of the IFN-g inducible proteasome subunits and of the peptide transporterTAP with that of HLA class I antigens in biopsies and cell lines from primary, recurrent, and metastatic HNSCC. Furthermore, APM component and HLA class I antigen expression in surgically removed lesions were correlated with the course of the disease in order to assess the clinical significance of deficient expression of these molecules. Results: A high frequency of LMP2, LMP7, andTAP1down-regulation or loss was found in tumor lesions and cell lines obtained from HNSCC cancer patients. These defects could be corrected by incubating cells with IFN-g. Furthermore, LMP2, LMP7,TAP1,TAP2, and HLA class I antigen expression rates in primary HNSCC lesions were found to predict overall survival. Lastly, the level of LMP7 expression was significantly associated with disease recurrence at 2 years. Conclusions: Our results suggest that the analysis of APM component expression in HNSCC lesions can provide useful prognostic information in patients with HNSCC.

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“…Down-regulation of HLA-I has been reported in a variety of malignancies (Esteban et al, 1996), including a significant percentage of colorectal cancers and its precursor adenomas (Cordon et al, 1991;Garrido et al, 1993;Lopez-Nevot et al, 1989;Moller et al, 1991b;Momburg et al, 1986;Tsioulias et al, 1993) and may result in a worse clinical outcome. This correlation has indeed been observed in a number of malignancies, such as breast cancer (Concha et al, 1991), melanoma (van Duinen et al, 1988), and laryngeal carcinoma (Esteban et al, 1996) but not for colorectal cancer (Cordon et al, 1991;Lopez-Nevot et al, 1989;Moller et al, 1991b;Momburg et al, 1986;Stein et al, 1988). Immunohistochemical studies on HLA-I expression in (colorectal) cancer most com-monly investigated the expression of the entire HLA-ABC/␤2m complex using the antibody W6/32.…”

mentioning

confidence: 99%

Down-Regulation of HLA-A Expression Correlates with a Better Prognosis in Colorectal Cancer Patients

Menon

Morreau

Tollenaar

et al. 2002

Laboratory Investigation

117

104

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SUMMARY:To evaluate the prognostic impact of human leukocyte antigen class I (HLA-I) expression on immune surveillance in colorectal cancer, we studied 88 curatively resected tumors for HLA-A and HLA-B/C expression and correlated these data to clinical and histopathological parameters. HLA-A was normal (all tumor cells had HLA expression) in 32%, reduced (HLA-negative and -positive tumor cells coexisted) in 56%, or absent (no tumor cells expressed HLA) in 12% of evaluable cases. HLA-B/C was normal in 47%, reduced in 47%, and absent in 7% of the cases. Considering both markers, total HLA-I expression was normal in 27%, reduced in 63%, absent in 7%, and could not be evaluated in 3% of the cases due to absent HLA-A expression in tumor and normal cells. Down-regulation of HLA-A expression significantly correlated with a lower tumor stage (p ϭ 0.005), mucinous tumors (p ϭ 0.05), a lower incidence of recurrences (p ϭ 0.03), and a longer disease-free survival (p ϭ 0.02). Down-regulation of HLA-B/C expression correlated with a lower tumor stage (p Ͻ 0.001) and a longer disease-free survival (p ϭ 0.04). In multivariate analysis, HLA-A down-regulation was the only prognostic factor correlated with a longer disease-free survival (p ϭ 0.02). Six tumors were negative for HLA-A and -B/C and did not recur during follow-up. Therefore, we analyzed microsatellite instability (MSI) in these cases. Three of these six tumors indeed showed down-regulation of MLH-1, MSH-2, or MSH-6, indicating a MSI-high phenotype. Beta-2-microglobulin protein expression was lost in five of six of the HLA-I-negative cases, but frame shift mutations in three repetitive sequences in ␤2-microglobulin were absent. In contrast, loss of MLH-1, MSH-2, and MSH-6-protein expression was only observed in two of nine matched controls with reduced or normal HLA-A and -B/C expression. Our data showed that HLA-I was down-regulated in 72% of colorectal cancers and provided independent prognostic information for a longer disease-free survival. The better prognosis may be caused by elimination of HLA-negative cells by natural killer cells or by an attenuated tumor aggressiveness, as is seen in tumors with a MSI-high phenotype. (Lab Invest 2002, 82:1725-1733.

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MHC class I antigens and tumour-infiltrating leucocytes in laryngeal cancer: long-term follow-up

Cited by 22 publications

References 35 publications

HLA Class I Antigen Down-regulation in Primary Laryngeal Squamous Cell Carcinoma Lesions as a Poor Prognostic Marker

HLA Class I Antigen Down-regulation in Primary Laryngeal Squamous Cell Carcinoma Lesions as a Poor Prognostic Marker

Defects in the Human Leukocyte Antigen Class I Antigen Processing Machinery in Head and Neck Squamous Cell Carcinoma: Association with Clinical Outcome

Down-Regulation of HLA-A Expression Correlates with a Better Prognosis in Colorectal Cancer Patients

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