A Method for Predicting Drugs That Can Boost the Efficacy of Immune Checkpoint Blockade

Overview

Journal Nat Immunol

Date 2024 Mar 19

PMID 38499799

Authors

Yun Xia

Xin Li

Nana Bie

Wen Pan

Ya-Ru Miao

Mei Yang

Yan Gao

Chuang Chen

Hanqing Liu

Lu Gan

An-Yuan Guo

Affiliations

Soon will be listed here.

Abstract

Combination therapy is a promising therapeutic strategy to enhance the efficacy of immune checkpoint blockade (ICB); however, predicting drugs for effective combination is challenging. Here we developed a general data-driven method called CM-Drug for screening compounds that can boost ICB treatment efficacy based on core and minor gene sets identified between responsive and nonresponsive samples in ICB therapy. The CM-Drug method was validated using melanoma and lung cancer mouse models, with combined therapeutic efficacy demonstrated in eight of nine predicted compounds. Among these compounds, taltirelin had the strongest synergistic effect. Mechanistic analysis and experimental verification demonstrated that taltirelin can stimulate CD8 T cells and is mediated by the induction of thyroid-stimulating hormone. This study provides an effective and general method for predicting and evaluating drugs for combination therapy and identifies candidate compounds for future ICB combination therapy.

Citing Articles

Inhibitory Fcγ receptor deletion enhances CD8 T cell stemness increasing anti-PD-1 therapy responsiveness against glioblastoma.

Ku K, Kim C, Kim Y, Kang B, La J, Kang I J Immunother Cancer. 2024; 12(10).

PMID: 39461881 PMC: 11529582. DOI: 10.1136/jitc-2024-009449.

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