Recent Advances in Our Understanding of HLA-G Biology: Lessons from a Wide Spectrum of Human Diseases

Morandi, Fabio; Rizzo, Roberta; Fainardi, Enrico; Rouas‐Freiss, Nathalie; Pistoia, Vito

doi:10.1155/2016/4326495

Cited by 109 publications

(107 citation statements)

References 95 publications

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“…Its clinical relevance in cancer is supported by the following observations: (i) HLA-G expression is associated with malignant transformation and is never observed in healthy surrounding tissues; (ii) HLA-G is found to be expressed in liquid and solid tumors of high histological grades and advanced clinical stages; and (iii) use of HLA-G as a prognostic marker has been proposed since HLA-G expression in biopsies and/or high levels of sHLA-G in plasma of patients have been significantly correlated with poor prognosis in different types of cancer. 31 Characterization of intratumor heterogeneity targeting checkpoint such as PD1/PDL1 and HLA-G/ILT2/ILT4 is important for immunotherapy. For 20 years, the use in kidney cancer of interleukin-2 and interferon aimed at stimulating T cell responses, have resulted in dramatic regression of metastases, including lung metastases.…”

Section: Discussionmentioning

confidence: 99%

Intratumor heterogeneity of immune checkpoints in primary renal cell cancer: Focus on HLA-G/ILT2/ILT4

et al. 2017

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The establishment and maintenance of anti-tumor immune responses are the objectives of cancer immunotherapy. Despite recent promising advances, the effectiveness of these approaches has been limited by the multiple immunosuppressive mechanisms developed by tumors (checkpoint). The aim of the present study was to demonstrate intratumor heterogeneity at the levels of immune escape strategies and tumor-host relationships. We focused on well-known checkpoints such as PD1/PDL1 and on a new checkpoint involving HLA-G and its receptors ILT2/ILT4. A prospective study was performed on 19 renal-cell carcinoma patients that were included during hospitalization for surgical tumor resection. Different areas of the tumor were collected for each patient and subjected to both immunohistochemical and flow cytometry analysis. Immune cells from peripheral blood were concomitantly analyzed for each patient. Our results show the heterogeneous expression of PD1/PDL1 and HLA-G/ILT in the various areas of the same tumor. Intratumor heterogeneity was found both at tumor cell and infiltrating immune cell levels. From a clinical point of view, this work highlights the functional redundancies of checkpoints and the need to adapt personalized poly-immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Intratumor heterogeneity of immune checkpoints in primary renal cell cancer: Focus on HLA-G/ILT2/ILT4

et al. 2017

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“…For instance, in tumors, HLA-G expression can be used as an immune escape mechanism, whereas HLA-G expression by grafted tissues may delay allograft rejection [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

Genetic association between HLA-G 14-bp polymorphism and diseases: A systematic review and meta-analysis

et al. 2018

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“…This results in decreased tumor immunogenicity, which is consequently associated with increased malignancy, metastasis formation, worse prognosis, and poorer response to (immuno-)therapies [34][35][36][37]. 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].…”

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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Recent Advances in Our Understanding of HLA-G Biology: Lessons from a Wide Spectrum of Human Diseases

Cited by 109 publications

References 95 publications

Intratumor heterogeneity of immune checkpoints in primary renal cell cancer: Focus on HLA-G/ILT2/ILT4

Intratumor heterogeneity of immune checkpoints in primary renal cell cancer: Focus on HLA-G/ILT2/ILT4

Genetic association between HLA-G 14-bp polymorphism and diseases: A systematic review and meta-analysis

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

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