T cell receptor gamma/delta expression on lymphocyte populations of breast cancer patients

Alam, Sadaf; Clark, James S.; Leech, Vanessa; Whitford, P.; George, W.D.; Campbell, Angus

doi:10.1016/0165-2478(92)90127-a

Cited by 19 publications

(12 citation statements)

References 16 publications

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“…In our series, the presence of mononuclear inflammatory cell infiltrate in the breast tissues with lesions concurs with previous reports [2][3][4] and also reflects ongoing immune responses against the neoplastic cells. The presence of mononuclear inflammatory cell infiltrate also suggests that the genetically damaged ductal cells have sufficient immunogenicity to recruit immunocytes.…”

Section: Discussionsupporting

confidence: 92%

“…It also suggests that some cases of benign proliferative breast disease may represent precursors for ductal carcinoma in situ. The presence of both B and T lymphocytes in the neoplastic lesions of the breast is in agreement with previous reports, [2][3][4] and suggests the participation of both cell-mediated and humoral immunity in mammary carcinogenesis. Most of the mononuclear inflammatory cell infiltrate was composed of CD3+ T cells, which coincides with the findings of others 3 and reflects increased T cell proliferation.…”

Section: Discussionsupporting

confidence: 92%

“…Lymphocytic infiltration is usually seen in hereditary ductal carcinoma in situ and infiltrating ductal carcinoma. [2][3][4][5][6] In premalignant lesions that occur in prophylactically removed breast tissue from patients who are at a high familial risk of breast cancer, lobulitis, with a predominance of T cells, was found in 51% of patients with prophylactically removed breast tissue. These findings imply an immune reaction to unidentified antigen, possibly as part of an early carcinogenic event.…”

mentioning

confidence: 99%

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Analysis of the mononuclear inflammatory cell infiltrate in the normal breast, benign proliferative breast disease, in situ and infiltrating ductal breast carcinomas: preliminary observations

Hussein

2006

J Clin Pathol

109

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

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Analysis of the mononuclear inflammatory cell infiltrate in the normal breast, benign proliferative breast disease, in situ and infiltrating ductal breast carcinomas: preliminary observations

Hussein

2006

J Clin Pathol

109

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“…gd T cells have been consistently identified and isolated from the TIL population in various types of cancers, including breast carcinoma (57). In this study, we show that TCRVg9 + T cells are present in biopsies of human mammary-infiltrating carcinomas with a similar proportion to NK cells, suggesting their attraction from peripheral blood to tumor site.…”

Section: Discussionmentioning

confidence: 53%

Stimulated γδ T Cells Increase the In Vivo Efficacy of Trastuzumab in HER-2+ Breast Cancer

Capietto

Martinet

Fournié

2011

The Journal of Immunology

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One fourth of women with HER-2+ metastatic breast carcinoma are treated with a combination regimen with trastuzumab, but the frequent resistance to this Ab requires definition of new means to improve its bioactivity. The mechanisms of action of trastuzumab involve several pathways including Ab-dependent cellular cytotoxicity. Because human γδ T lymphocytes mediate Ab-dependent cellular cytotoxicity and can be activated further by phosphoantigens, these cells are prone to improve the efficacy of Abs, as recently demonstrated for CD20+ B cell lymphomas. Whether this concept applies as well with carcinomas remained to be demonstrated in vivo, however. In this study, we asked whether a combination of trastuzumab and phosphoantigen-stimulated γδ lymphocytes increases the efficacy of trastuzumab against HER-2+ breast carcinoma cell lines in vivo. We report that repeated infusions of this combination had a better efficacy than that of trastuzumab alone against HER-2+ mammary carcinoma xenografts in mice. In these models, reduction of tumor growth was observed together with trastuzumab opsonization of HER-2+ cells and tumor infiltration by γδ lymphocytes. In addition in humans, the mammary carcinomas of 27 of 30 patients showed significant γδ T cell infiltrates. Altogether, these findings indicate that combination of trastuzumab and stimulated γδ cells represents a new strategy to improve the efficacy of Herceptin (trastuzumab) in HER-2+ breast cancer.

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“…At each site, the various cells perform specific functions. For example, Vγ δ cells can: kill tumor targets (Leclercq et al, 1990); attack breast cancer cells (Alam et al, 1992); react against chemically induced skin cancers (Girardi et al, 2003); destroy ovarian serous carcinoma cells (Raspollini et al, 2005), and can recognize and destroy viral proteins (Lundberg and Splitter, 2000).…”

Section: Introductionmentioning

confidence: 99%

Alterations in CD4⁺, CD8⁺, Vγ3, Vγδ, and/or VαβT-Lymphocyte Expression in Lymphoid Tissues of Progeny AfterIn UteroExposure to Benzo(α)pyrene

Urso

Wirsiy

Zhang

et al. 2008

Journal of Immunotoxicology

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That benzo alpha)pyrene (Balpha P) decreases both humoral and cell-mediated immunity, and leads to increases in progeny tumor development after in utero insult, suggests that T- and B-lymphocytes are made defective in exposed offspring. In the study here, C3H mice were injected once with Balpha P (150 microg/g BW) at day 12 of pregnancy and progeny lymphoid tissues were excised during gestation (day 18; GD18) or at 1 or 6 weeks post-partum. The isolated lymphoid cells were analyzed by flow cytometry/immunofluorescence or assessed for function. In Balpha P-exposed fetuses, thymic Thy1(+) cell levels were decreased (relative to levels in organs of corn oil-exposed dam progeny). In addition, for up to 6 weeks post-birth, CD4(+)CD8(+) (double positive; DP) cells were virtually absent and levels of CD4(-)CD8(-) (double negative; DN) cells were consistently at epsilon 90%. With regard to single positive (SP) cells, CD4(+) cell levels were also decreased in tissues at GD18 up through 6 weeks post-birth; CD8(+) cell levels were increased, but only in pups at 1-week and 6-weeks post-birth. In 1-week-old progeny, spleen CD8(+) cell levels were quantitatively unchanged, though CD4(+) levels were reduced 2-4-fold and CD4(-)CD8(-) DN levels significantly increased. With respect to TCRs, fetal levels of thymic CD3Vgamma(3)(+) and CD3Vgamma delta(+) cells were decreased; levels of CD3Valphabeta cells were only slightly depressed. The latter results contrast sharply with a strong reduction in CD3Valphabeta cells in the fetal livers of Balpha P-exposed progeny. Interestingly, these livers also strongly evidenced a presence of BalphaP-7,8-dihydrodiol-9,10-epoxide metabolite. When assessed for any change in function, the CD4(+), Thy1(+) cells isolated from Balpha P-exposed progeny tissues responded weakly (relative to controls) to ConA and in an allogeneic MLR. Taken in totality, the results here strengthen our original hypothesis that BalphaP can create a favorable milieu for tumor growth progression in progeny of exposed mothers by affecting development of sufficient numbers of functional lymphocytes in the offspring.

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T cell receptor gamma/delta expression on lymphocyte populations of breast cancer patients

Cited by 19 publications

References 16 publications

Analysis of the mononuclear inflammatory cell infiltrate in the normal breast, benign proliferative breast disease, in situ and infiltrating ductal breast carcinomas: preliminary observations

Analysis of the mononuclear inflammatory cell infiltrate in the normal breast, benign proliferative breast disease, in situ and infiltrating ductal breast carcinomas: preliminary observations

Stimulated γδ T Cells Increase the In Vivo Efficacy of Trastuzumab in HER-2+ Breast Cancer

Alterations in CD4⁺, CD8⁺, Vγ3, Vγδ, and/or VαβT-Lymphocyte Expression in Lymphoid Tissues of Progeny AfterIn UteroExposure to Benzo(α)pyrene

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T cell receptor gamma/delta expression on lymphocyte populations of breast cancer patients

Cited by 19 publications

References 16 publications

Analysis of the mononuclear inflammatory cell infiltrate in the normal breast, benign proliferative breast disease, in situ and infiltrating ductal breast carcinomas: preliminary observations

Analysis of the mononuclear inflammatory cell infiltrate in the normal breast, benign proliferative breast disease, in situ and infiltrating ductal breast carcinomas: preliminary observations

Stimulated γδ T Cells Increase the In Vivo Efficacy of Trastuzumab in HER-2+ Breast Cancer

Alterations in CD4+, CD8+, Vγ3, Vγδ, and/or VαβT-Lymphocyte Expression in Lymphoid Tissues of Progeny AfterIn UteroExposure to Benzo(α)pyrene

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Alterations in CD4⁺, CD8⁺, Vγ3, Vγδ, and/or VαβT-Lymphocyte Expression in Lymphoid Tissues of Progeny AfterIn UteroExposure to Benzo(α)pyrene