T cell-mediated immune therapies have emerged as a promising treatment modality in different malignancies including colorectal cancer(CRC).However,only a fraction of patients currently respond to treatment.Understandi...T cell-mediated immune therapies have emerged as a promising treatment modality in different malignancies including colorectal cancer(CRC).However,only a fraction of patients currently respond to treatment.Understanding the lack of responses and finding biomarkers with predictive value is of great importance.There is evidence that CRC is a heterogeneous disease and several classification systems have been proposed that are based on genomic instability,immune cell infiltration,stromal content and molecular subtypes of gene expression.Human leukocyte antigen class Ⅰ(HLA-Ⅰ)plays a pivotal role in presenting processed antigens to T lymphocytes,including tumour antigens.These molecules are frequently lost in different types of cancers,including CRC resulting in tumour immune escape from cytotoxic T lymphocytes during the natural history of cancer development.The aim of this review is to(i)summarize the prevalence and molecular mechanisms behind HLA-Ⅰ loss in CRC,(ii)discuss HLA-Ⅰ expression/loss in the context of the newly identified CRC molecular subtypes,(iii)analyze the HLA-Ⅰ phenotypes of CRC metastases disseminated via blood or the lymphatic system,(iv)discuss strategies to recover/circumvent HLA-I expression/loss and finally(v)review the role of HLA class Ⅱ(HLA-Ⅱ)in CRC prognosis.展开更多
基金supported by Ethics Committees and Scientific Committeessupported by the grants from Instituto de Salud Carlos ill,co-financed by European Regional Development Fund(FEDER)[PI11/01386,PI14/01978,PI16/00752,PI17/00197 and PI18/00826]supported by the Consejeria de Salud,Junta de Andaluda through the contract‘Nicolas Monardes’[C-0013-2018].
文摘T cell-mediated immune therapies have emerged as a promising treatment modality in different malignancies including colorectal cancer(CRC).However,only a fraction of patients currently respond to treatment.Understanding the lack of responses and finding biomarkers with predictive value is of great importance.There is evidence that CRC is a heterogeneous disease and several classification systems have been proposed that are based on genomic instability,immune cell infiltration,stromal content and molecular subtypes of gene expression.Human leukocyte antigen class Ⅰ(HLA-Ⅰ)plays a pivotal role in presenting processed antigens to T lymphocytes,including tumour antigens.These molecules are frequently lost in different types of cancers,including CRC resulting in tumour immune escape from cytotoxic T lymphocytes during the natural history of cancer development.The aim of this review is to(i)summarize the prevalence and molecular mechanisms behind HLA-Ⅰ loss in CRC,(ii)discuss HLA-Ⅰ expression/loss in the context of the newly identified CRC molecular subtypes,(iii)analyze the HLA-Ⅰ phenotypes of CRC metastases disseminated via blood or the lymphatic system,(iv)discuss strategies to recover/circumvent HLA-I expression/loss and finally(v)review the role of HLA class Ⅱ(HLA-Ⅱ)in CRC prognosis.
