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

Abstract

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.

• Authors: Se-Hoon Lee, Yeongmin Kim, Bu-Nam Jeon, Gihyeon Kim, Jinyoung Sohn, Youngmin Yoon, Sujeong Kim, Yunjae Kim, Hyemin Kim, Hongui Cha, Na-Eun Lee, Hyunsuk Yang, Joo-Yeon Chung, A-Reum Jeong, Yun Yeon Kim, Sang Gyun Kim, Yeonhee Seo, Sehhoon Park, Hyun Ae Jung, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn, Hansoo Park, Kyoung Wan Yoon
• Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (Adv Sci (Weinh)) Vol. 10 Issue 17 Pg. e2204378 (06 2023) ISSN: 2198-3844 [Electronic] Germany
• PMID: 37097643 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.

Chemical References

• Immune Checkpoint Inhibitors
• Intercellular Adhesion Molecule-1

Topics

• Humans
• Mice
• Animals
• CD8-Positive T-Lymphocytes
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Immune Checkpoint Inhibitors (pharmacology, therapeutic use)
• Lung Neoplasms (drug therapy, pathology)
• Intercellular Adhesion Molecule-1