Immunomodulatory Effects of RANK/RANKL Blockade in Patients with Cancer

Author:

Nasrollahi Elham1ORCID,Davar Diwakar12ORCID

Affiliation:

1. 1University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, Pennsylvania.

2. 2University of Pittsburgh, Pittsburgh, Pennsylvania.

Abstract

Abstract In cancer, multiple factors converge upon receptor activator of nuclear factor κB (RANK) and its ligand (RANKL) signaling to promote the development of bone metastases; agents that inhibit RANKL signaling reduce skeletal-related events (SRE) in patients with cancer. In addition, RANKL signaling is important in augmenting the ability of dendritic cells (DC) to stimulate both naïve T-cell proliferation and the survival of RANK+ T cells. In this issue, Chang and colleagues using high-dimensional cytometry to evaluate immunomodulatory effects of denosumab in patients with advanced solid, observe early on treatment changes in multiple compartments, and greater effects in patients receiving concurrent chemotherapy or steroids. See related article by Chang et al., p. 453 (4).

Publisher

American Association for Cancer Research (AACR)

Reference7 articles.

1. Targeting the RANKL/RANK/OPG axis for cancer therapy;Ming;Front Oncol,2020

2. Bisphosphonates or RANK-ligand-inhibitors for men with prostate cancer and bone metastases: a network meta-analysis;Jakob;Cochrane Database Syst Rev,2020

3. Adjuvant bisphosphonates or RANK-ligand inhibitors for patients with breast cancer and bone metastases: a systematic review and network meta-analysis;Tesfamariam;Crit Rev Oncol Hematol,2019

4. Immune modulation with RANKL blockade through denosumab treatment in patients with cancer;Chang,2024

5. RANKL blockade improves efficacy of PD1-PD-L1 blockade or dual PD1-PD-L1 and CTLA4 blockade in mouse models of cancer;Ahern;Oncoimmunology,2018

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