Linoleoyl-lysophosphatidylcholine Suppresses Immune-related Adverse Events Due to Immune Checkpoint Blockade

Overview

Journal medRxiv

Date 2024 Aug 16

PMID 39148854

Authors

Ian T Mathews

Priyanka Saminathan

Mir Henglin

Mingyue Liu

Namratha Nadig

Camille Fang

Kysha Mercader

Serena J Chee

Allison M Campbell

Abhijit A Patel

Saumya Tiwari

Jeramie D Watrous

Karthik Ramesh

Martina Dicker

Khoi Dao

Melissa A Meyer

Pekka Jousilahti

Aki S Havulinna

Teemu Niiranen

Veikko Salomaa

Leo A B Joosten

Mihai G Netea

Pan Zheng

Mitchell Kronenberg

Sandip Pravin Patel

J Silvio Gutkind

Christian Ottensmeier

Tao Long

Susan M Kaech

Catherine C Hedrick

Susan Cheng

Mohit Jain

Sonia Sharma

Affiliations

Soon will be listed here.

Abstract

Immune related adverse events (irAEs) after immune checkpoint blockade (ICB) therapy occur in a significant proportion of cancer patients. To date, the circulating mediators of ICB-irAEs remain poorly understood. Using non-targeted mass spectrometry, here we identify the circulating bio-active lipid linoleoyl-lysophosphatidylcholine (LPC 18:2) as a modulator of ICB-irAEs. In three independent human studies of ICB treatment for solid tumor, loss of circulating LPC 18:2 preceded the development of severe irAEs across multiple organ systems. In both healthy humans and severe ICB-irAE patients, low LPC 18:2 was found to correlate with high blood neutrophilia. Reduced LPC 18:2 biosynthesis was confirmed in preclinical ICB-irAE models, and LPC 18:2 supplementation suppressed neutrophilia and tissue inflammation without impacting ICB anti-tumor response. Results indicate that circulating LPC 18:2 suppresses human ICB-irAEs, and LPC 18:2 supplementation may improve ICB outcomes by preventing severe inflammation while maintaining anti-tumor immunity.

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