Flow cytometric analysis of tumour infiltrating lymphocyte activation and tumour cell MHC Class I and II expression in breast cancer patients

Whitford, P.; George, W.D.; Campbell, Angus

doi:10.1016/0304-3835(92)90174-t

Cited by 38 publications

(18 citation statements)

References 14 publications

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“…Previous studies have demonstrated that most TIL contain a significantly higher proportion of lymphocytes bearing CD25 or HLA-DR than. [13][14][15] These findings suggest that TIL are activated by the stimulation of tumorassociated antigen. In this study, we examined TIL and PBL in colorectal cancer patients and found that the expression of α1 and α2 integrins was increased, whereas α4, α6, and 1 subunits were downregulated in TIL compared with findings in PBL.…”

Section: Statisticsmentioning

confidence: 85%

“…8 Previous studies have shown that tumor-infiltrating lymphocytes (TIL) in solid tumors consist of considerably different lymphocyte populations from those in autologous peripheral blood lymphocytes (PBL). [9][10][11][12][13][14][15] In most tumors, TIL contain more CD8(ϩ) T cells than PBL, although the ratio differs in each histologic type of tumors. [9][10][11][12] TIL have also been reported to express cell activation markers, such as CD25 (interleukin [IL]-2 receptor), 13 human leukocyte antigen (HLA)-DR 13-15 at significantly higher levels than PBL.…”

Section: Introductionmentioning

confidence: 99%

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Functional expression of β1 and β2 integrins on tumor infiltrating lymphocytes (TILs) in colorectal cancer

Kitayama

Nagawa

Nakayama

et al. 1999

Journal of Gastroenterology

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Integrins play an important role in various lymphocyte functions. In this study, tumor-infiltrating lymphocytes (TIL) were isolated from colorectal cancer tissues and the expression of beta1 and beta2 integrins on the TIL was quantitatively examined with two-color flow cytometry. In comparison with peripheral blood lymphocytes (PBL), TIL expressed a lower level of common beta1 chain (CD29) in both CD4 and CD8 subpopulations. Among the associated alpha chains, the expressions of alpha1 (CD49a) and alpha2 (CD49b) were slightly higher in TIL than in PBL, whereas alpha4 (CD49d) and alpha6 (CD49f) were markedly downregulated in TIL. Both alphaL (CD11a) and beta2 (CD18) were reduced in CD8(+) TIL but not in CD4(+) TIL. TIL with the CD8(+) cytotoxic phenotype showed significantly decreased binding to purified intracellular adhesion molecules (ICAM)-1, and vascular adhesion cell molecule (VCAM)-1, and HT29 colon cancer cells, compared with the in counterparts in PBL. The peculiar expression pattern and functional down regulation of these integrins may explain why TIL in colorectal cancer cannot eradicate the malignant cells.

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Section: Statisticsmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Functional expression of β1 and β2 integrins on tumor infiltrating lymphocytes (TILs) in colorectal cancer

Kitayama

Nagawa

Nakayama

et al. 1999

Journal of Gastroenterology

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“…The expression of HLA-DR, CD25 and CD71 (transferrin receptor), on the majority of tumour-infiltrating lymphocytes (TILs) from breast cancers suggested that the T cells have been activated in vivo (Whitford, et al, 1990; Chin et al, 1992;Whitford et al, 1992;Ostenstad et al, 1994). However, the failure to contain tumour growth suggests deficiencies in TIL function or numbers.…”

mentioning

confidence: 99%

High incidence of interleukin 10 mRNA but not interleukin 2 mRNA detected in human breast tumours

Venetsanakos

Beckman²,

Bradley³

et al. 1997

Br J Cancer

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Summary Despite the presence of a lymphocytic infiltrate in solid cancers, the failure for tumour growth to be contained suggests an inadequate immune response to the tumour. Poor cytotoxicity exerted by tumour-infiltrating lymphocytes (TILs) against tumour cells in vitro, combined with continued tumour growth in vivo, suggests deficiencies in TIL function or numbers. Various theories have been postulated to explain how tumour cells may escape immunosurveillance and control. One of the many hypotheses is the failure of production of cytokines, which are necessary for T cells to mediate their function. Thus, the expression of cytokine mRNA in human breast tumour sections was investigated by reverse transcriptase polymerase chain reaction (RT-PCR) with cytokine-specific primers. A relatively consistent finding was detection of interleukin (IL) 10 mRNA among the tumours. No IL-2 and little IL-4 mRNA was detected in the tumours. IL-6 and IL-10 mRNA was detected in only one and two of the normal breast tissues respectively. IL-2, IL-4 and tumour necrosis factor (TNF)-a mRNA was not detected in any of the normal breast tissues. The reduced function of TILs may be related to IL-10, which has known inhibitory effects on T-cell activation.

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“…23 Moreover, there is no previous report describing the expression of these integrin expressions on freshly isolated TIL. However, previous studies have demonstrated that most TIL contain a significantly higher proportion of lymphocytes bearing CD25 or HLA-DR.. [5][6][7] These findings suggest that TIL are somewhat activated by stimulation with tumor-associated antigen. In addition, it has been reported that ␤1 and ␤2 integrins are up-regulated in T cells in inflammatory tissues such as those seen in dermatitis 24 or thyroiditis, 25 or the synovial fluid of rheumatoid arthritis.…”

Section: Discussionmentioning

confidence: 82%

“…[1][2][3][4][5][6][7] In most tumors, TIL contain more CD8 ϩ T cells than do PBL, although the ratio differs among histologic types of tumors. [1][2][3][4] Moreover, TIL have been reported to express significantly higher levels of cell activation markers, such as CD25 (IL-2 receptor) 5 or HLA-DR, 5-7 than PBL, suggesting that TIL are somewhat activated by tumor associated antigens.…”

mentioning

confidence: 99%

Functional Down-Regulation of ?1 and ?2 Integrins on Lamina Propria Lymphocytes (LPL) and Tumor-Infiltrating Lymphocytes (TIL) in Colorectal Cancer Patients

et al. 1999

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Integrins play an important role in various lymphocyte functions. In this study, we isolated lamina propria lymphocytes (LPL) and tumor-infiltrating lymphocytes (TIL) from normal and malignant tissues in patients with colorectal cancer, and examined the expression of beta1 and beta2 integrins on these lymphocytes quantitatively with two-color flow cytometry. Both LPL and TIL expressed a lower level of common beta1 chain (CD29) in CD4 and CD8 subpopulations than did peripheral blood lymphocytes (PBL). Among the associated alpha chains, the expression levels of alpha1 (CD49a) and alpha2 (CD49b) were slightly higher, whereas those of alpha4 (CD49d) and alpha6 (CD49f) were markedly reduced in LPL and TIL. No significant differences were observed in expressions of any alpha1 integrin chains between these two lymphocytes populations. Similarly, both alphaL (CD11a) and beta2 (CD18) were down-regulated in TIL and LPL with CD8+ cytotoxic phenotype, but not in those with CD4+ phenotype. CD8+ TIL expressed a slightly but significantly higher level of alphaLbeta2 than did CD8+ LPL. CD8+ LPL and CD8+ TIL consistently showed significantly decreased binding to purified ICAM-1, VCAM-1 and HT29 colon cancer cells as compared with CD8+ PBL. Although CD8+ TIL showed a slightly higher level of adhesion to these substrates than did CD8+ LPL, the level was much lower than that in PBL. The expression pattern and functional down-regulation of these integrins may be one of the reasons why TIL cannot eradicate the cancer cells in colorectal cancer.

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Flow cytometric analysis of tumour infiltrating lymphocyte activation and tumour cell MHC Class I and II expression in breast cancer patients

Cited by 38 publications

References 14 publications

Functional expression of β1 and β2 integrins on tumor infiltrating lymphocytes (TILs) in colorectal cancer

Functional expression of β1 and β2 integrins on tumor infiltrating lymphocytes (TILs) in colorectal cancer

High incidence of interleukin 10 mRNA but not interleukin 2 mRNA detected in human breast tumours

Functional Down-Regulation of ?1 and ?2 Integrins on Lamina Propria Lymphocytes (LPL) and Tumor-Infiltrating Lymphocytes (TIL) in Colorectal Cancer Patients

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