Perforin expression in lymphocytes infiltrated to human colorectal cancer

Nakanishi, Hiroyuki; Monden, Takushi; Morimoto, Hiroki; Kobayashi, T.; Shimano, Takashi; Mori, Takesada

doi:10.1038/bjc.1991.283

Cited by 15 publications

(10 citation statements)

References 22 publications

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“…5 6 As Mulder et al find that the number of TCR + lymphocytes decreased in Dukes's A carcinomas, their results suggest that TCR t downregulation in TIL is a relatively early event in the interaction between a tumour and the immune system. In contrast, they describe an increase in the numbers of GrB expressing lymphocytes in the early stage of colorectal tumours, similar to earlier observations by Nakanishi et al 9 The authors infer that as the expression of this molecule involved in the cytolysis of tumour cells requires both TCR triggering and signalling via a costimulatory receptor some immune stimulation still takes place in Dukes's A carcinoma. In Dukes's D carcinomas, however, GrB expressing cells had disappeared from the tumour tissue, which can explain the lack of cytotoxic activity of TIL cells.…”

Section: Ignals From Lymphocytes In Colon Cancersupporting

confidence: 87%

Signals from lymphocytes in colon cancer.

Kiessling¹

1997

Gut

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Section: Ignals From Lymphocytes In Colon Cancersupporting

confidence: 87%

Signals from lymphocytes in colon cancer.

Kiessling¹

1997

Gut

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“…The factors driving the CD8 + T cell proliferation in colorectal carcinomas are not known but are likely to be the tumour cells themselves. As the CD8 + IEL are perforin negative [7], they may have a regulatory role, rather than a cytotoxic function. The CD4 + T cells also proliferate more when in contact with the tumour.…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that in vitro , CD8 + T‐IEL are able to spontaneously lyse colon carcinoma cell lines [6]. Around 20% of the stromal, but almost none of the intraepithelial CD8 + T cells express perforin in Dukes’ A carcinomas, decreasing to just 3% in the stroma in Dukes’ C cases [7]. Carcinoma‐infiltrating Vδ1 + T cells also lyse colon carcinoma cell lines [8], recognizing MICA and MICB on the tumour cells [9], and it has been shown in mice that Vα14 + NK T cells lyse tumour cells [10].…”

Section: Introductionmentioning

confidence: 99%

Proliferation of T-cell subsets that contact tumour cells in colorectal cancer

Golby

Chinyama

Spencer

2002

Clinical and Experimental Immunology

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It has been known for decades that solid malignancies in humans are associated with an infiltrate of inflammatory cells. A number of studies have found a clear positive correlation between the density of the lymphoid infiltrate and the prognosis of the patient [1][2][3][4]. This, together with the partial oligoclonality of carcinoma-infiltrating T cells [5], indicates that local immune responses to the tumours are likely to be occurring, although the precise nature of the response, and the reason for the survival of the tumours despite the anti-tumour response, are not known. It has been shown that in vitro, CD8 + T-IEL are able to spontaneously lyse colon carcinoma cell lines [6]. Around 20% of the stromal, but almost none of the intraepithelial CD8 + T cells express perforin in Dukes' A carcinomas, decreasing to just 3% in the stroma in Dukes' C cases [7]. Carcinoma-infiltrating Vd1 + T cells also lyse colon carcinoma cell lines [8], recognizing MICA and MICB on the tumour cells [9], and it has been shown in mice that Va14 + NK T cells lyse tumour cells [10]. As CD1, the target for human Va24 + NK T cells, is expressed on the intestinal epithelium [11], these cells may also respond to colorectal carcinoma cells.The phenotypes of the infiltrating lymphocytes have been investigated, and the proportions of CD4 + , CD8 + , TCRab + and TCRgd + cells reported vary considerably in different studies [12][13][14][15][16][17][18][19]. However, overall, it appears that CD8 + T cells localize to the epithelium, as in the normal gut. It has also been shown that the numbers of CD56 + and CD57 + NK T cells are increased within colorectal carcinomas compared with the normal gut [20,21].To increase understanding of the anti-tumour immune response, we have asked which subsets of tumour-infiltrating T cells are stimulated to proliferate in the T-IEL compartment, where T cells are in direct contact with the tumour, and in the stroma. We have also compared the proliferation frequencies observed for each T-cell subset with that observed in areas of maximal T cell stimulation in tonsils and Peyer's patches. In addition, T cells within intact cultured explants of colorectal carcinomas were studied to determine whether the T cell response is supported by factors in the tumour microenvironment. The explant model described here will also enable future studies of the functional relationship between the stromal and lymphoid elements of the tumour microenvironment. MATERIALS AND METHODS Tissues SUMMARYWe have investigated the proliferation rates of T-cell subsets in colorectal carcinomas using immunohistochemistry. It was found that the tumour-infiltrating T cells in contact with the tumour cells have a significantly higher frequency of proliferation than those in the stroma. In particular, the CD8 + intraepithelial lymphocytes (T-IEL) within the tumours have a significantly higher frequency of proliferation in comparison with CD8 + T cells in the stromal compartment or in any normal mucosal lymphoid tissues. It is possible that the proli...

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“…T cells infiltrating along the invasive margin were also reported to be mainly CD45RO + memory/effector‐type T cells 10. Infiltrating T cells also included cytotoxic T cells (CTL) carrying cytoplasmic perforin granules 11. Our observations suggest an occurrence of host anti‐tumor immune responses in colorectal cancer that affects prognosis.…”

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confidence: 99%

Selective infiltration of CCR5⁺CXCR3⁺ T lymphocytes in human colorectal carcinoma

Musha

Ohtani

Mizoi

et al. 2005

Intl Journal of Cancer

133

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T cell infiltration in colorectal cancer is associated with a favorable prognosis, suggesting an occurrence of a certain degree of anti-tumor immunity. T helper type 1 (Th1) and Th2 cells are now known to selectively express CC-chemokine receptor 5 (CCR5)/ CXC-chemokine receptor 3 (CXCR3) and CCR4, respectively. To clarify the mechanism of T cell infiltration, we examined in situ expression of these chemokine receptors and their respective chemokine ligands in 40 cases of human colorectal cancer. Immunohistochemistry showed a predominant accumulation of T cells expressing CCR5 and CXCR3 mainly along the invasive margin, whereas those expressing CCR4 were rare. Flow cytometric analysis showed that more than half of CD8 1 T cells and a fraction of CD4 1 cells isolated from fresh tumor tissues co-expressed CCR5 and CXCR3, and CD8 1 T cells and CD4 1 cells predominantly produced interferon-c (IFN-c) over interleukin-4 (IL-4) after in vitro stimulation. RANTES/CCL5, a ligand of CCR5, was localized within infiltrating CD8 1 T cells in a granular pattern, whereas IP-10/CXCL10, a ligand of CXCR3, was localized in cancer cells and macrophages along the invasive margin. These data were consistent with an active recruitment of T cells expressing CCR5 or CXCR3 into the invasive margin of colorectal cancer. With the previous clinicopathological studies showing a favorable prognostic impact of T cell infiltration in colorectal cancer, our study supports the occurrence of a certain level of Th1-shifted cellular immune responses in human colorectal cancer. ' 2005 Wiley-Liss, Inc.

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Perforin expression in lymphocytes infiltrated to human colorectal cancer

Cited by 15 publications

References 22 publications

Signals from lymphocytes in colon cancer.

Signals from lymphocytes in colon cancer.

Proliferation of T-cell subsets that contact tumour cells in colorectal cancer

Selective infiltration of CCR5⁺CXCR3⁺ T lymphocytes in human colorectal carcinoma

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Perforin expression in lymphocytes infiltrated to human colorectal cancer

Cited by 15 publications

References 22 publications

Signals from lymphocytes in colon cancer.

Signals from lymphocytes in colon cancer.

Proliferation of T-cell subsets that contact tumour cells in colorectal cancer

Selective infiltration of CCR5+CXCR3+ T lymphocytes in human colorectal carcinoma

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Selective infiltration of CCR5⁺CXCR3⁺ T lymphocytes in human colorectal carcinoma