Perspectives on immune checkpoint ligands: expression, regulation, and clinical implications
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In the tumor microenvironment, immune checkpoint ligands(ICLs) must be expressed in order to trigger the inhibitory signalvia immune checkpoint receptors (ICRs). Although ICL expressionfrequently occurs in a manner intrinsic to tumor cells,extrinsic factors derived from the tumor microenvironment canfine-tune ICL expression by tumor cells or prompt non-tumorcells, including immune cells. Considering the extensive interactionbetween T cells and other immune cells within the tumormicroenvironment, ICL expression on immune cells can be assignificant as that of ICLs on tumor cells in promoting antitumorimmune responses. Here, we introduce various regulatorsknown to induce or suppress ICL expression in either tumorcells or immune cells, and concise mechanisms relevant totheir induction. Finally, we focus on the clinical significance ofunderstanding the mechanisms of ICLs for an optimized immunotherapyfor individual cancer patients.
Abstract
In the tumor microenvironment, immune checkpoint ligands(ICLs) must be expressed in order to trigger the inhibitory signalvia immune checkpoint receptors (ICRs). Although ICL expressionfrequently occurs in a manner intrinsic to tumor cells,extrinsic factors derived from the tumor microenvironment canfine-tune ICL expression by tumor cells or prompt non-tumorcells, including immune cells. Considering the extensive interactionbetween T cells and other immune cells within the tumormicroenvironment, ICL expression on immune cells can be assignificant as that of ICLs on tumor cells in promoting antitumorimmune responses. Here, we introduce various regulatorsknown to induce or suppress ICL expression in either tumorcells or immune cells, and concise mechanisms relevant totheir induction. Finally, we focus on the clinical significance ofunderstanding the mechanisms of ICLs for an optimized immunotherapyfor individual cancer patients.
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