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. 2021 Feb 16;9(2):e001230. doi: 10.1136/jitc-2020-001230

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© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See https://creativecommons.org/licenses/by/4.0/.

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Tumor microenvironment (TME) characterized by canonical or non-canonical programmed cell death 1 (PD-1) signaling. Based on the different status of PD-1 signaling, we classified TME into two types: canonical PD-1 signaling-enriched TME (left) and non-canonical PD-1 signaling-enriched TME (right). Canonical PD-1 signaling-enriched TME is characterized by high infiltration of CD8 T cells and conventional CD4 T cells. Biomarkers for PD-1 blockade therapy including PD-L1 and TMB may work optimally in this type TME. However, biomarkers for non-canonical PD-1 signaling-enriched TME remains largely unknown. DC, dendritic cell; NK, natural killer; TAM, tumor-associated macrophages.