Cancer immune escape:MHCexpression in primary tumours versus metastases

Abstract

<p id="d120333e225">Tumours can escape T‐cell responses by losing major histocompatibility complex ( <span style="fixed-case">MHC</span>)/ human leucocyte antigen ( <span style="fixed-case">HLA</span>) class I molecules. In the early stages of cancer development, primary tumours are composed of homogeneous <span style="fixed-case">HLA</span> class I‐positive cancer cells. Subsequently, infiltration of the tumour by T cells generates a vast diversity of tumour clones with different <span style="fixed-case">MHC</span> class I expressions. A Darwinian type of T‐cell‐mediated immune selection results in a tumour composed solely of <span style="fixed-case">MHC</span> class I‐negative cells. Metastatic colonization is a highly complex phenomenon in which T lymphocytes and natural killer cells play a major role. We have obtained evidence that the <span style="fixed-case">MHC</span> class I phenotype of metastatic colonies can be highly diverse and is not necessarily the same as that of the primary tumour. The molecular mechanisms responsible for <span style="fixed-case">MHC</span>/ <span style="fixed-case">HLA</span> class I alterations are an important determinant of the clinical response to cancer immunotherapy. Hence, immunotherapy can successfully up‐regulate <span style="fixed-case">MHC</span>/ <span style="fixed-case">HLA</span> class I expression if the alteration is reversible (‘soft’), leading to T‐cell‐mediated tumour regression. In contrast, it cannot recover this expression if the alteration is irreversible (‘hard’), when tumour cells escape T‐cell‐mediated destruction with subsequent cancer progression. This review summarizes clinical and experimental data on the complexity of immune escape mechanisms used by tumour cells to avoid T and natural killer cell responses. We also provide in‐depth analysis of the nature of <span style="fixed-case">MHC</span>/ <span style="fixed-case">HLA</span> class I changes during metastatic colonization and contribute evidence of the enormous diversity of <span style="fixed-case">MHC</span>/ <span style="fixed-case">HLA</span> class I phenotypes that can be produced by tumour cells during this process. </p>