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. 2021 Jan 4;13(1):134. doi: 10.3390/cancers13010134

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© 2021 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Schematic representation of antigen processing and presentation in cancer immune evasion and immune re-activation by ICIs and manipulation of intracellular antigen processing. (Panel A) tumor antigens are processed by the proteasome but then destroyed by ER aminopeptidases ERAP1 or ERAP2 resulting in lack of presentation on the cell surface. Overexpression of PD-L1 on the cancer cell surface downregulates cytotoxic T-lymphocyte responses. Synergism between these two mechanisms results in efficient immune evasion by the tumor. (Panel B) Immune-checkpoint inhibitors can help activate T cells but lack of tumor antigen presentation limits cytotoxic responses. (Panel C) inhibition of ERAP1 and ERAP2 can help rescue tumor-associated antigenic peptides from destruction and promote their presentation, which, in combination with ICI treatment, can help re-activate T cell cytotoxic responses against the tumor.