Oral immune tolerance mediated by suppressor T cells may be responsible for the poorer prognosis of foregut cancers

Larkin, John; Tangney, Mark; Collins, Christopher G.; Casey, Garrett; O’Brien, Michael; Soden, Declan M.; O’Sullivan, Gerald C.

doi:10.1016/j.mehy.2005.09.021

Cited by 6 publications

(12 citation statements)

References 26 publications

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“…In animal models, the presence of numerous maternal cells or soluble antigens in breast milk could induce tolerance to maternal cells (7,8,13), while ingestion of tumor fragments could give the tumor cells a growth advantage (10)(11)(12). These results suggest that breast milk containing maternal leukemic cells, as well as normal cells, might facilitate tolerance to and promote growth of maternal leukemic cells transmitted to the infant during pregnancy.…”

Section: Discussionmentioning

confidence: 94%

“…Breast milk contains a number of maternal antigens and leukocytes. Another report in mice showed that oral feeding of tumor fragments could confer a growth advantage on, and induce immune tolerance to, tumor cells (10)(11)(12). These findings suggest that breast feeding after delivery could promote a survival advantage for and tolerance to maternal BCR-ABL-positive cells, in the event of their transmission to the infant.…”

Section: Introductionmentioning

confidence: 93%

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Detection of BCR-ABL-Positive Cells in the Colostrum of a Pregnant Patient with Chronic Myeloid Leukemia

et al. 2011

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 93%

Detection of BCR-ABL-Positive Cells in the Colostrum of a Pregnant Patient with Chronic Myeloid Leukemia

et al. 2011

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“…CD4 + T cells play a central role in initiating and maintaining anticancer immune responses (30). however, regulatory CD4 + CD25 + T cells that express FoxP3 have also been shown to inhibit anti-tumor effector T cells (3-7) and may, therefore, contribute to the growth of human tumors (6,(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)). An increase in Treg cell populations has been observed in different types of cancers, such as pancreas (18), ovarian tumors (17), metastatic melanoma (23) and head and neck cancer (12,24,25).…”

Section: Discussionmentioning

confidence: 99%

“…Treg cells are characterized by the constitutive expression of a transmembrane protein, CD25 (the α-chain of the receptor for interleukin-2), cytotoxic T lymphocyte antigen-4 (CTLA-4) and forkhead transcription factor (FoxP3) (3)(4)(5)(6)(7)(8)(9). Previous results showed that Treg cells are potent inhibitors of anti-tumor immune response and are associated with poor prognosis in different types of cancer (6,(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). The depletion of CD4 + CD25 + Treg cells has been shown to result in a slower tumor growth rate (13).…”

Section: Introductionmentioning

confidence: 99%

T regulatory cell markers in oral squamous cell carcinoma: Relationship with survival and tumor aggressiveness

Moreira

Fulgêncio²,

Mendonça³

et al. 2010

Oncology Letters

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Abstract. Tumor-infiltrating lymphocytes (TILs) are a heterogeneous cell family which plays an important role in tumorassociated immune response. Of these, T regulatory (Treg) cells have also been shown to inhibit anti-tumor response. We aimed to evaluate the expression of T regulatory cell markers (CD4, CD25, CTLA-4 and FoxP3) in samples of oral cavity squamous cell carcinoma (OCSCC) and lip SCC (LSCC) by immunohistochemistry. The relationship of Treg markers with survival data and the proliferative index were also evaluated. We observed similar numbers of CD4-, CD25-and FoxP3+ cells in OCSCC and LSCC. On the other hand, numbers of CTLA-4 + cells were significantly lower in OCSCC than in LSCC. OCSCC samples with high numbers of CD4 exhibited a high proliferative index, while samples with high CTLA-4 counts demonstrated a low tumoral proliferative index. A log-rank test showed that patients with OCSCC that presented high counts of CD4 showed a significantly decreased survival compared with patients with low cell counts. In contrast, high CD25 + cell counts were associated with increased survival. Our results suggest an association of CD4 with poor prognosis, while CD25 expression is related with favorable prognosis. These findings result from the heterogeneity of TIL subsets that display an antagonistic role in tumor immune cell response.

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“…The JBS murine fibrosarcoma [13] was grown in tissue culture flasks at 37°C in a humidified atmosphere of 5% CO 2 , in DMEM (Dulbecco's Minimal Essential Medium –Sigma-Aldrich, Dublin, Ireland). The tissue culture media were supplemented with 10% iron-supplemented donor calf serum, 50 µg/ml gentamycin, 300 µg/ml L-glutamine, and 10 mM HEPES (1-Piperazineethane sulfonic acid, 4-(2-hydroxyethyl) monosodium salt), pH 7.4.…”

Section: Methodsmentioning

confidence: 99%

Oral Tolerance to Cancer Can Be Abrogated by T Regulatory Cell Inhibition

et al. 2014

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Oral administration of tumour cells induces an immune hypo-responsiveness known as oral tolerance. We have previously shown that oral tolerance to a cancer is tumour antigen specific, non-cross-reactive and confers a tumour growth advantage. We investigated the utilisation of regulatory T cell (Treg) depletion on oral tolerance to a cancer and its ability to control tumour growth. Balb/C mice were gavage fed homogenised tumour tissue – JBS fibrosarcoma (to induce oral tolerance to a cancer), or PBS as control. Growth of subcutaneous JBS tumours were measured; splenic tissue excised and flow cytometry used to quantify and compare systemic Tregs and T effector (Teff) cell populations. Prior to and/or following tumour feeding, mice were intraperitoneally administered anti-CD25, to inactivate systemic Tregs, or given isotype antibody as a control. Mice which were orally tolerised prior to subcutaneous tumour induction, displayed significantly higher systemic Treg levels (14% vs 6%) and faster tumour growth rates than controls (p<0.05). Complete regression of tumours were only seen after Treg inactivation and occurred in all groups - this was not inhibited by tumour feeding. The cure rates for Treg inactivation were 60% during tolerisation, 75% during tumour growth and 100% during inactivation for both tolerisation and tumour growth. Depletion of Tregs gave rise to an increased number of Teff cells. Treg depletion post-tolerisation and post-tumour induction led to the complete regression of all tumours on tumour bearing mice. Oral administration of tumour tissue, confers a tumour growth advantage and is accompanied by an increase in systemic Treg levels. The administration of anti-CD25 Ab decreased Treg numbers and caused an increase in Teffs. Most notably Treg cell inhibition overcame established oral tolerance with consequent tumor regression, especially relevant to foregut cancers where oral tolerance is likely to be induced by the shedding of tumour tissue into the gut.

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Oral immune tolerance mediated by suppressor T cells may be responsible for the poorer prognosis of foregut cancers

Cited by 6 publications

References 26 publications

Detection of BCR-ABL-Positive Cells in the Colostrum of a Pregnant Patient with Chronic Myeloid Leukemia

Detection of BCR-ABL-Positive Cells in the Colostrum of a Pregnant Patient with Chronic Myeloid Leukemia

T regulatory cell markers in oral squamous cell carcinoma: Relationship with survival and tumor aggressiveness

Oral Tolerance to Cancer Can Be Abrogated by T Regulatory Cell Inhibition

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