4.8 Article

Intracellular Adhesion Molecule-1 Improves Responsiveness to Immune Checkpoint Inhibitor by Activating CD8+ T Cells

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ADVANCED SCIENCE
卷 10, 期 17, 页码 -

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WILEY
DOI: 10.1002/advs.202204378

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anti-tumor effects; CD8(+) T cells; chemokine (CXC motif) ligand 13; immune checkpoint inhibitor; soluble ICAM-1

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High levels of ICAM-1 in tumors and plasma are associated with prolonged survival in non-small cell lung cancer patients treated with anti-PD-1 or anti-PD-L1. Further studies reveal that sICAM-1 enhances the efficacy of anti-PD-1 by activating cytotoxic T cells, and CXCL13 might be involved in the ICAM-1-mediated anti-tumor pathway. Combinatorial therapy with sICAM-1 and anti-PD-1 shows promise in converting anti-PD-1-resistant tumors to responsive ones in preclinical studies.
Immune checkpoint inhibitor (ICI) clinically benefits cancer treatment. However, the ICI responses are only achieved in a subset of patients, and the underlying mechanisms of the limited response remain unclear. 160 patients with non-small cell lung cancer treated with anti-programmed cell death protein-1 (anti-PD-1) or anti-programmed death ligand-1 (anti-PD-L1) are analyzed to understand the early determinants of response to ICI. It is observed that high levels of intracellular adhesion molecule-1 (ICAM-1) in tumors and plasma of patients are associated with prolonged survival. Further reverse translational studies using murine syngeneic tumor models reveal that soluble ICAM-1 (sICAM-1) is a key molecule that increases the efficacy of anti-PD-1 via activation of cytotoxic T cells. Moreover, chemokine (CXC motif) ligand 13 (CXCL13) in tumors and plasma is correlated with the level of ICAM-1 and ICI efficacy, suggesting that CXCL13 might be involved in the ICAM-1-mediated anti-tumor pathway. Using sICAM-1 alone and in combination with anti-PD-1 enhances anti-tumor efficacy in anti-PD-1-responsive tumors in murine models. Notably, combinatorial therapy with sICAM-1 and anti-PD-1 converts anti-PD-1-resistant tumors to responsive ones in a preclinical study. These findings provide a new immunotherapeutic strategy for treating cancers using ICAM-1.

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