Cancer Immunology: Immune Escape of Tumors—Expression and Regulation of HLA Class I Molecules and Its Role in Immunotherapies

Abstract

The addition of “avoiding immune destruction” to the hallmarks of cancer demonstrated the importance of cancer immunology and in particular the role of immune surveillance and escape from malignancies. However, the underlying mechanisms contributing to immune impairment and immune responses are diverse. Loss or reduced expression of the HLA class I molecules are major characteristics of human cancers resulting in an impaired recognition of tumor cells by CD8+ cytotoxic T lymphocytes. This is of clinical relevance and associated with worse patients outcome and limited efficacy of T-cell-based immunotherapies. Here, we summarize the role of HLA class I antigens in cancers by focusing on the underlying molecular mechanisms responsible for HLA class I defects, which are caused by either structural alterations or deregulation at the transcriptional, posttranscriptional, and posttranslational levels. In addition, the influence of HLA class I abnormalities to adaptive and acquired immunotherapy resistances will be described. The in-depth knowledge of the different strategies of malignancies leading to HLA class I defects can be applied to design more effective cancer immunotherapies.

Identification of RNA-binding protein hnRNP C targeting the 3’UTR of the TAP-associated glycoprotein tapasin in melanoma

“… 42 Since the HLA-I pathway inhibition by hnRNP C overexpression might affect the immune cell infiltration in melanoma cells, the correlation between hnRNP C expression and immune cell infiltration was investigated using 67 metastatic melanoma cases from the TCGA-SKCM dataset, which were divided into hnRNP C high and hnRNP C low expressors. It is well established that CD8 + T cells recognize antigens presented by HLA-I, 43 and HLA-I expression affects CD8 + T cell activation and is associated with the level of T cell infiltration. As shown in Figure 6g , the frequency of CD8 + T cell infiltration was inversely correlated with the hnRNP C high group, suggesting that hnRNP C overexpression might impair the CD8 + T cell-mediated tumor recognition due to downregulation of the HLA-I pathway.…”

Machine learning developed a macrophage signature for predicting prognosis, immune infiltration and immunotherapy features in head and neck squamous cell carcinoma

“…In addition, cluster 2 had higher matrix, immune, and in ltration scores than cluster 1, and the functional pathways of immune cells and the expression of HLA molecules were enriched in cluster 2. Owing to immune editing, the absence or downregulation of HLA molecules is a common early event in cancer occurrence, which can lead to impaired recognition of tumor cells by cytotoxic T cells, resulting in immune escape and is closely associated with tumor recurrence and metastasis [30]. The ICI gene was predominantly expressed in cluster 2, which was closely linked to malignant characteristics such as epithelial-mesenchymal transition, angiogenesis, and the dissemination and invasion of malignancies.…”

A novel HLA‐C*17 variant, HLA‐C*17:01:01:29, identified in a healthy individual from Greece

“…Next-generation sequencing (NGS) technologies have greatly advanced our understanding of immune genetics, carrying extensive implications for personalized medicine, organ transplantation, and the development of precise immunotherapies. 1 Its broad application spans various fields, highlighting its deep and pivotal importance. 2 In this report the identification of the novel HLA-C*17:01:01:29 allele, is described.…”