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Please use this identifier to cite or link to this item: http://hdl.handle.net/10481/49150

Title: The Escape of Cancer from T Cell-Mediated Immune Surveillance: HLA Class I Loss and Tumor Tissue Architecture
Authors: Garrido Torres-Puchol, Federico
Perea, Francisco
Bernal Sánchez, Mónica
Sánchez Palencia Ramos, Abel
Aptsiauri, Natalia
Ruiz-Cabello, Francisco
Issue Date: 27-Feb-2017
Abstract: Tumor immune escape is associated with the loss of tumor HLA class I (HLA-I) expression commonly found in malignant cells. Accumulating evidence suggests that the efficacy of immunotherapy depends on the expression levels of HLA class I molecules on tumors cells. It also depends on the molecular mechanism underlying the loss of HLA expression, which could be reversible/“soft” or irreversible/“hard” due to genetic alterations in HLA, β2-microglobulin or IFN genes. Immune selection of HLA-I negative tumor cells harboring structural/irreversible alterations has been demonstrated after immunotherapy in cancer patients and in experimental cancer models. Here, we summarize recent findings indicating that tumor HLA-I loss also correlates with a reduced intra-tumor T cell infiltration and with a specific reorganization of tumor tissue. T cell immune selection of HLA-I negative tumors results in a clear separation between the stroma and the tumor parenchyma with leucocytes, macrophages and other mononuclear cells restrained outside the tumor mass. Better understanding of the structural and functional changes taking place in the tumor microenvironment may help to overcome cancer immune escape and improve the efficacy of different immunotherapeutic strategies. We also underline the urgent need for designing strategies to enhance tumor HLA class I expression that could improve tumor rejection by cytotoxic T-lymphocytes (CTL).
Sponsorship: This work was supported by the grants from Spanish Institute of Heath Carlos III (ISCIII, Instituto Carlos III) co-financed by European Union (FEDER-Fondo Europeo de Desarrollo Regional) (PI12/02031, PI08/1265, PI11/01022, PI11/01386, RETIC RD 06/020, RD09/0076/00165, PT13/0010/0039, PI14/01978, PI16/00752) and by the Junta de Andalucía in Spain (Groups CTS-143, CTS-695,CTS-3952, CVI-4740, PI 09/0382 grant).
Publisher: MDPI
Keywords: HLA class I loss
Tumor infiltrating lymphocytes (TILs)
Tumor immune escape
URI: http://hdl.handle.net/10481/49150
ISSN: 2076-393X
Rights : Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License
Citation: Garrido Torres-Puchol, F.; et al. The Escape of Cancer from T Cell-Mediated Immune Surveillance: HLA Class I Loss and Tumor Tissue Architecture. Vaccines, 5(1): 7 (2017). [http://hdl.handle.net/10481/49150]
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