Tumor cell expression of HLA-DM associates with a Th1 profile and predicts improved survival in breast carcinoma patients

Oldford, Sharon A.; Robb, J. Desmond; Codner, D.; Gadag, Veeresh; Watson, Peter H.; Drover, Sheila

doi:10.1093/intimm/dxl092

Cited by 82 publications

(86 citation statements)

References 46 publications

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“…Tumorassociated T cells can have different effects, depending on activation status. Th1-type T cells are associated with good outcome (99,(110)(111)(112)(113), while immunosuppressive Tregs are associated with tumor progression and poor prognosis (113)(114)(115)(116), and response to neoadjuvant therapy correlates with changes in Treg numbers (117). In addition, microenvironmental factors, including T cell status, may play a more prominent role in determining outcome in ER -and HER2 + tumors (99,118), while tumor proliferation is more closely correlated with outcome in ER + disease.…”

Section: Microenvironmental Heterogeneitymentioning

confidence: 99%

Breast cancer — one term, many entities?

Bertos¹,

Park²

2011

J. Clin. Invest.

191

140

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Breast cancer, rather than constituting a monolithic entity, comprises heterogeneous tumors with different clinical characteristics, disease courses, and responses to specific treatments. Tumor-intrinsic features, including classical histological and immunopathological classifications as well as more recently described molecular subtypes, separate breast tumors into multiple groups. Tumor-extrinsic features, including microenvironmental configuration, also have prognostic significance and further expand the list of tumor-defining variables. A better understanding of the features underlying heterogeneity, as well as of the mechanisms and consequences of their interactions, is essential to improve targeting of existing therapies and to develop novel agents addressing specific combinations of features.

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Section: Microenvironmental Heterogeneitymentioning

confidence: 99%

Breast cancer — one term, many entities?

Bertos¹,

Park²

2011

J. Clin. Invest.

191

140

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“…Interestingly, low levels of CLIP and increased DM expression on various tumors predicted better survival of afflicted individuals (38,39). This may relate to Th1 polarization of tumor-specific T cells as shown in DM + breast carcinoma patients (40).…”

Section: Discussionmentioning

confidence: 88%

Forced Expression of HLA-DM at the Surface of Dendritic Cells Increases Loading of Synthetic Peptides on MHC Class II Molecules and Modulates T Cell Responses

Pezeshki

Côté

Azar

et al. 2011

The Journal of Immunology

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Adoptive transfer of autologous dendritic cells (DCs) loaded with tumor-associated CD4 and CD8 T cell epitopes represents a promising avenue for the immunotherapy of cancer. In an effort to increase the loading of therapeutic synthetic peptides on MHC II molecules, we used a mutant of HLA-DM (DMY) devoid of its lysosomal sorting motif and that accumulates at the cell surface. Transfection of DMY into HLA-DR+ cells resulted in increased loading of the exogenously supplied HA307–318 peptide, as well as increased stimulation of HA-specific T cells. Also, on transduction in mouse and human DCs, DMY increased loading of HEL48–61 and of the tumor Ag-derived gp100174–190 peptides, respectively. Interestingly, expression of DMY at the surface of APCs favored Th1 differentiation over Th2. Finally, we found that DMY− and DMY+ mouse APCs differentially stimulated T cell hybridomas sensitive to the fine conformation of peptide–MHC II complexes. Taken together, our results suggest that the overexpression of HLA-DMY at the plasma membrane of DCs may improve quantitatively, but also qualitatively, the presentation of CD4 T cell epitopes in cellular vaccine therapies for cancer.

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“…These data suggest that Ii-and DMindependent class II antigen presentation pathways exist in these tumors as demonstrated previously in other malignant cells and non-professional APCs. 47,48 Ii-negative class II-expressing tumor cells have also been shown to be immunogenic, inducing antitumor immune responses. 49,50 Thus, Ii-negative/DR þ prostate tumor cells may directly present self-antigens to stimulate CD4 þ T cells.…”

Section: Discussionmentioning

confidence: 99%

HLA class II antigen presentation by prostate cancer cells

Younger

Amria

Jeffrey

et al. 2007

Prostate Cancer Prostatic Dis

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Prostate cancer is the second most commonly diagnosed cancer in men. Recent evidence suggests that reduced expression of target protein antigens and human leukocyte antigen (HLA) molecules is the predominant immune escape mechanism of malignant prostate tumor cells. The purpose of this study was to investigate the prospect of antigen specific immunotherapy against prostate cancer via the HLA class II pathway of immune recognition. Here, we show for the first time that prostate cancer cells express HLA class II proteins that are recognized by CD4 þ T cells. Prostate tumor cells transduced with class II molecules efficiently presented tumor-associated antigens/peptides to CD4 þ T cells. This data suggests that malignant prostate tumors can be targeted via the HLA class II pathway, and that class II-positive tumors could be employed for direct antigen presentation, and CD4 þ T-cell mediated tumor immunotherapy.

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Tumor cell expression of HLA-DM associates with a Th1 profile and predicts improved survival in breast carcinoma patients

Cited by 82 publications

References 46 publications

Breast cancer — one term, many entities?

Breast cancer — one term, many entities?

Forced Expression of HLA-DM at the Surface of Dendritic Cells Increases Loading of Synthetic Peptides on MHC Class II Molecules and Modulates T Cell Responses

HLA class II antigen presentation by prostate cancer cells

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