Quantitation of MHC antigen expression on colorectal tumours and its association with tumour progression

Durrant, LG; Ballantyne, KC; Armitage, N. C.; Robins, R. A.; Marksman, R A; Hardcastle, J D; Baldwin, R. W.

doi:10.1038/bjc.1987.218

Cited by 36 publications

(24 citation statements)

References 28 publications

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“…It has been reported that some colorectal carcinomas do not express MHC I antigens (Csiba et al, 1984;Umpleby et al, 1985;Momburg et al, 1986;Durrant et al, 1987), which is consistent with our results. In one study, the expression of MHC I was correlated to the degree of differentiation of the tumours (Momburg et al, 1986).…”

Section: Discussionsupporting

confidence: 83%

“…Poorly differentiated or aneuploid tumours expressed more of these antigens than well-differentiated or diploid tumours Tumour infiltration by mononuclear inflammatory cells 379 (Rognum et al, 1983;Durrant et al, 1987). However, no correlation between the expression of MHC I or II and the clinicopathological stage was found by others (Momburg et al, 1986;Durrant et al, 1987). In the present study, most of the tumours expressing MHC II were also heavily infiltrated by CD4+ cells, which is compatible with induction of MHC II expression by interferon-gamma produced by these cells.…”

Section: Discussionsupporting

confidence: 73%

“…The expression of the MHC II antigens of colorectal carcinoma cells varied considerably in different studies (Daar et al, 1982;Daar and Fabre, 1983;Csiba et al 1984;Momburg et al, 1986;Durrant et al, 1987). Poorly differentiated or aneuploid tumours expressed more of these antigens than well-differentiated or diploid tumours Tumour infiltration by mononuclear inflammatory cells 379 (Rognum et al, 1983;Durrant et al, 1987). However, no correlation between the expression of MHC I or II and the clinicopathological stage was found by others (Momburg et al, 1986;Durrant et al, 1987).…”

Section: Discussionmentioning

confidence: 82%

“…In one study, the expression of MHC I was correlated to the degree of differentiation of the tumours (Momburg et al, 1986). The expression of the MHC II antigens of colorectal carcinoma cells varied considerably in different studies (Daar et al, 1982;Daar and Fabre, 1983;Csiba et al 1984;Momburg et al, 1986;Durrant et al, 1987). Poorly differentiated or aneuploid tumours expressed more of these antigens than well-differentiated or diploid tumours Tumour infiltration by mononuclear inflammatory cells 379 (Rognum et al, 1983;Durrant et al, 1987).…”

Section: Discussionmentioning

confidence: 99%

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Infiltration of mononuclear inflammatory cells into primary colorectal carcinomas: an immunohistological analysis

Håkansson

Adell²,

Boeryd³

et al. 1997

Br J Cancer

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Infiltration of mononuclear inflammatory cells into primary colorectal carcinomas: an immunohistological analysis L HAkansson1, G Adell1, B Boeryd2, F Sjogren3 and R Sjodahl4Departments of 'Oncology, 2Pathology, 3Clinical Immunology and 4Surgery, University Hospital of Linkoping, S-581 85 Linkoping, Sweden Summary Local immunoregulation mediated by mononuclear tumour-infiltrating cells is considered of importance for tumour progression of colorectal cancer, although the balance between immunosuppressor and cytotoxic activities is unclear. Colorectal cancers from 26 patients were investigated using a panel of monoclonal antibodies in order to identify subsets of mononuclear inflammatory cells and to study their pattern of distribution in relation to tumour stage and cytotoxic immune reactivity against the tumour. In all but five tumours, mononuclear cells, lymphocytes or monocytes were present in fairly large numbers, particularly in the stroma. The infiltration of CD4+ mononuclear cells predominated over the CD8+ subset. Infiltration near the tumour cells was found in four cancers only. Stromal infiltration of CD11c+ macrophages was found in all but eight tumours. Small regressive areas, in which the histological architecture of the tumours was broken down, were found in 17 tumours with intense or moderate infiltration by CD4+ lymphocytes or CD1 1 c+ macrophages. Probably this destruction of tumour tissue was caused by cytotoxic activity of the tumour-infiltrating mononuclear cells. In Dukes' class A and B tumours, CD4+ lymphocytes predominated over CD4+ cells with macrophage morphology, but the latter were increasingly found in Dukes' class C and D disease. The occurrence of MHC Il-positive macrophages and lymphocytes in different Dukes' classes was similar to that of CD4+ cells. In contrast to this, CD11c+ and CD11a+ cells were more frequent in Dukes' A and B class tumours compared with Dukes' C and D. Four out of nine tumours of the latter stages showed a poor inflammatory reaction. The interpretation of our results is that the subsets of tumourinfiltrating mononuclear cells change with advancing Dukes' class and that the local immune control is gradually broken down in progressive tumour growth, even if some cytotoxic activity is still present.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Infiltration of mononuclear inflammatory cells into primary colorectal carcinomas: an immunohistological analysis

Håkansson

Adell²,

Boeryd³

et al. 1997

Br J Cancer

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“…Our observed frequency of alterations in HLA-I is in agreement with other studies and suggests that our study cohort is comparable with other reported populations (Cordon et al, 1991;Durrant et al, 1987;Kaklamanis et al, 1992;Lopez-Nevot et al, 1989;Moller et al, 1991aMoller et al, , 1991bMoore et al, 1986;Smith et al, 1989;Stein et al, 1988;van den Ingh et al, 1987). The improved prognosis for patients with tumors that had down-regulated HLA-I, and HLA-A in particular, is a novel finding and argues against the importance of T-cell-mediated immune surveillance.…”

Section: Discussionsupporting

confidence: 82%

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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Effect of anti-CD3 antibody on the generation of interleukin-2-activated lymphocytes from tumor tissues of gastrointestinal cancer

Ohta

Kikuchi

Ogata

et al. 1992

Cancer

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Background. The efficiency of anti-CD3 antibody (OKT3) for adoptive immunotherapy using lymphokineactivated killer (LAK) cells generated from tumor-infiltrating lymphocytes (TIL), regional lymph node lymphocytes (RLNL), and peripheral blood lymphocytes (PBL) was investigated. Methods. TIL, RLNL, and PBL derived from 39 patients with gastrointestinal cancers (16 gastric cancers, 17 colorectal cancers, and 6 esophageal cancers) were cultured for 4 weeks with 200 U/ml of recombinant interleukin-2. To one group, solid-phase 10 pg/ml OKT3 was added during the initial culture period (day 2 or 4). Cytotoxicity against K562 cells (NK-like activity) and Daudi cells (LAK activity) and the phenotypes of effector cells generated after culturing for 2-3 weeks were studied, Results. Proliferative responses were significantly increased by OKT3 in each type of effector cell (P < 0.01); in particular, TIL expanded more by OKT3 than PBL and RLNL (P < 0.01). The population of CD8' CDllb-cytotoxic T-cells in OKT3-stimulated groups was significantly larger than that in unstimulated groups (P < 0.011, whereas no differences were observed with CD4+ cells (helper/inducer T-cells) and CD8' CDllb' cells (suppressor T-cells). OKT3 enhanced the NK-like activity of TIL and PBL but did not affect their LAK activity. OKT3 suppressed the NK and LAK activity of RLNL. Conclusions. OKT3 stimulation did not significantly enhance the LAK activity, but the authors propose that OKT3 could be an effective addition to adoptive immunotherapy using TIL due to an increased proliferation

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Quantitation of MHC antigen expression on colorectal tumours and its association with tumour progression

Cited by 36 publications

References 28 publications

Infiltration of mononuclear inflammatory cells into primary colorectal carcinomas: an immunohistological analysis

Infiltration of mononuclear inflammatory cells into primary colorectal carcinomas: an immunohistological analysis

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

Effect of anti-CD3 antibody on the generation of interleukin-2-activated lymphocytes from tumor tissues of gastrointestinal cancer

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