The prognostic impact of soluble and vesicular HLA-G and its relationship to circulating tumor cells in neoadjuvant treated breast cancer patients

König, Lisa; Kasimir‐Bauer, Sabine; Hoffmann, Oliver; Bittner, Ann‐Kathrin; Wagner, Bettina; Manvailer, Luis Felipe Santos; Schramm, Sabine; Bànkfalvi, Àgnes; Giebel, Bernd; Kimmig, Rainer; Horn, Peter A.; Rebmann, Vera

doi:10.1016/j.humimm.2016.01.002

Cited by 71 publications

(93 citation statements)

References 48 publications

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“…Interestingly, the surrounding lymphocytes and histiocytes were HLA-G positive and correlation with disease progression suggests an association of these immunoreactive patterns of HRS cells and the tumor microenvironment on disease outcome. Aberrant HLA-G expression was also described in other hematological malignancies such as non-Hodgkin lymphoma (Sebti et al 2007), chronic lymphatic leukemia (Sebti et al 2007), and multiple myeloma (Leleu et al 2005) as well as in solid tumors, such as breast cancer (Konig et al 2016; Rebmann et al 2003), and non-small cell lung cancer, particularly in advanced disease stages (Ben Amor et al 2016; Yan et al 2015). …”

Section: Introductionmentioning

confidence: 92%

HLA-G peptide preferences change in transformed cells: impact on the binding motif

et al. 2018

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HLA-G is known for its strictly restricted tissue distribution. HLA-G expression could be detected in immune privileged organs and many tumor entities such as leukemia, multiple myeloma, and non-Hodgkin and Hodgkin’s lymphoma. This functional variability from mediation of immune tolerance to facilitation of tumor immune evasion strategies might translate to a differential NK cell inhibition between immune-privileged organs and tumor cells. The biophysical invariability of the HLA-G heavy chain and its contrary diversity in immunity implicates a strong influence of the bound peptides on the pHLA-G structure. The aim was to determine if HLA-G displays a tissue-specific peptide repertoire. Therefore, using soluble sHLA-G technology, we analyzed the K562 and HDLM-2 peptide repertoires. Although both cell lines possess a comparable proteome and recruit HLA-G-restricted peptides through the same peptide-loading pathway, the peptide features appear to be cell specific. HDLM-2 derived HLA-G peptides are anchored by an Arg at p1 and K562-derived peptides are anchored by a Lys. At p2, no anchor motif could be determined while peptides were anchored at pΩ with a Leu and showed an auxiliary anchor motif Pro at p3. To appreciate if the peptide anchor alterations are due to a cell-specific differential peptidome, we performed analysis of peptide availability within the different cell types. Yet, the comparison of the cell-specific proteome and HLA-G-restricted ligandome clearly demonstrates a tissue-specific peptide selection by HLA-G molecules. This exclusive and unexpected observation suggests an exquisite immune function of HLA-G.

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Section: Introductionmentioning

confidence: 92%

HLA-G peptide preferences change in transformed cells: impact on the binding motif

et al. 2018

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“…On the contrary, high levels of soluble HLA-G in blood stream suggests a better scenario. This is the first demonstration of a differential role of soluble fractions of HLA-G, depending on encapsulation or not within EVs (7,12).…”

mentioning

confidence: 71%

“…It is well known that tumor cells release many factors to orchestrate their progression and EVs play a relevant role in this phenomenon. A few other groups have observed HLA-G within EVs in a tumor microenvironment (11)(12)(13). Tumor EVs stimulate angiogenesis, tumor cells growth, favor the metastatization process and induce immune escape (14).…”

mentioning

confidence: 99%

Immunosuppressive role of extracellular vesicles: HLA-G, an important player

Grange

Camussi

2017

Ann. Transl. Med.

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“…While downregulation of HLA class I antigens negatively interferes with T-cell responses only, the expression of the non-classical HLA-G, which consists of 4 membrane-bound and 3 soluble isoforms [38], results in escape of tumor cells from both NK-and T-cell-mediated recognition [39]. In BC, increased HLA-G expression levels were found [40] which were not only associated with poor prognosis [41,42] but also with therapy response of BC treated with neoadjuvant chemotherapy [40]. In addition, high soluble HLA-G concentrations were detected in the serum of BC patients and correlated with occurrence of metastasis, suggesting their usefulness as prognostic biomarker [43].…”

Section: Abnormal Expression Of Mhc Class I and Components Of The Antmentioning

confidence: 99%

The Role of Immune Escape and Immune Cell Infiltration in Breast Cancer

2018

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While detailed analysis of aberrant cancer cell signaling pathways and changes in cancer cell DNA has dominated the field of breast cancer biology for years, there now exists increasing evidence that the tumor microenvironment (TME) including tumor-infiltrating immune cells support the growth and development of breast cancer and further facilitate invasion and metastasis formation as well as sensitivity to drug therapy. Furthermore, breast cancer cells have developed different strategies to escape surveillance from the adaptive and innate immune system. These include loss of expression of immunostimulatory molecules, gain of expression of immunoinhibitory molecules such as PD-L1 and HLA-G, and altered expression of components involved in apoptosis. Furthermore, the composition of the TME plays a key role in breast cancer development and treatment response. In this review we will focus on i) the different immune evasion mechanisms used by breast cancer cells, ii) the role of immune cell infiltration in this disease, and (iii) implication for breast cancer-based immunotherapies.

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The prognostic impact of soluble and vesicular HLA-G and its relationship to circulating tumor cells in neoadjuvant treated breast cancer patients

Cited by 71 publications

References 48 publications

HLA-G peptide preferences change in transformed cells: impact on the binding motif

HLA-G peptide preferences change in transformed cells: impact on the binding motif

Immunosuppressive role of extracellular vesicles: HLA-G, an important player

The Role of Immune Escape and Immune Cell Infiltration in Breast Cancer

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