The Escape of Cancer from T Cell-Mediated Immune Surveillance: HLA Class I Loss and Tumor Tissue Architecture
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AuthorGarrido Torres-Puchol, Federico; Perea, Francisco; Bernal Sánchez, Mónica; Sánchez Palencia Ramos, Abel; Aptsiauri, Natalia; Ruiz-Cabello, Francisco
HLA class I lossTumor infiltrating lymphocytes (TILs)Tumor immune escape
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]
SponsorshipThis 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).
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).