Editorial: Bone metastasis in the milieu of osteoimmunology

COPYRIGHT © 2023 Sharma, Ponzetti and Siddiqui. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. TYPE Editorial PUBLISHED 07 August 2023 DOI 10.3389/fimmu.2023.1265434

Cancer Genome Atlas (TCGA) revealed three high-risk CRLncs and three low-risk CRLncs involved in OS prognosis and immune microenvironment. In a drug-sensitive study, authors found four potent drugs: AUY922, bortezomib, and Z.LLNle.CHO is sensitive to low-risk and lenalidomide for the high-risk OS group. Furthermore, Guo et al., by using consensus clustering analysis, identified 25 cancer stem cell-related genes and classified OS into three (CSC cluster A, B, and C) molecular subtypes. Among 25 CSC-related genes, authors emphasized MEF2C as a significant player in immune infiltration and tumor cell stemness which correlated with patient survival. A recent study in bladder cancer also revealed MEF2C as a prognostic factor and putative role in immune modulation (1). Moreover, the authors established a unique CSC scoring system that could be beneficial in assessing tumor-microenvironment (TME) immune infiltration and for personalized immunotherapy of OS patients.
The role of chemokines and cytokines is highly correlated with tissue-specific tropism, niche formation, and colonization of cancer cells (2). However, interleukins (ILs) are well known for the inflammatory response in various diseases and tumor microenvironments. Tong et al. highlight the pivotal role of the IL-1 family in prostate cancer (PCa) progression and bone metastasis. As PCa exhibits the highest incidence of bone metastasis, authors attractively connect IL-1 family-mediated inflammation with PCa bone metastasis progression. They have covered several ILs' functions as anti-and pro-tumorigenic activity. Additionally, the authors provide a glimpse of ILs' diverse role in colonization, dormancy, reactivation, angiogenesis, and bone remodeling. In a transcriptome-based multiplex drug repurposing study, Chang et al. validated a new scheme to screen specific candidate compounds to prevent bone metastasis of castration resistance prostate cancer (CRPC) patients. After a battery of comprehensive analysis, two compounds, namely CID 190453/ mulberroside C and CID 78177919/terrestrosin D, show selective and potent binding with Secreted phosphoprotein 1 (SPP1), also known as Osteopontin, that can regulate the M2 macrophageassociated PCa-bone metastatic genes. Elevated expression of SPP1 is highly correlated with immune cell infiltration and poor survival in various cancers (3).
Li et al. performed a study on 171 non-small cell lung cancer (NSCLC)-bone metastatic patients and categorized them into four groups. Among all groups, DI, i.e., patients receiving a combination of denosumab with immune checkpoint inhibitors (ICIs), reveals safe, highest drug efficacy and survival of bone metastatic NSCLC patients with minimal side effects. Recently, in a clinical trial, dostarlimab, an anti-PD-1 monoclonal antibody, showed complete remission in all advanced rectal carcinoma patients (4).
In a series of therapeutic efficacy of ICIs against bone metastasis, Yu et al. summarize the recent studies on various mechanisms of chemoresistance and vulnerable targets, including myeloid-derived suppressor cells (MDSCs). In this review, authors emphasize the status of different immunotherapeutic targets such as programmed death-ligands/receptors (PD-1/PD-L1) and cytotoxic T lymphocyteassociated protein 4 (CTLA-4) and clinical trials of ICIs for OS patients. Similarly, a case report by Asano et al. demonstrates that the combination of neutralizing antibodies (nivolumab for PD-1 and ipilimumab for CTLA-4) attenuates bone metastasis in a renal cell carcinoma (RCC) patient. A fracture in the humerus diaphysis with osteolytic changes due to bone metastasis and lung metastasis. No sign of tumor or metastasis in the histopathological examination after four courses of ICIs treatment.
As a primary goal of this Research Topic to improve knowledge and significant advancement of bone metastasis in osteoimmunology, Kähkönen et al. summarize and short-listed 24 anti-bone metastatic therapies by utilizing a novel 1stOncology database based on osteoimmuno-oncology (OIO) concept. This OIO approach deals with the interaction patterns between cancer, bone, and immune cells. Twenty drugs were short-listed from 1498 for breast cancer and 746 for prostate cancer. The authors provide an innovative approach and robust platform to identify therapies for immune activation and prevention or attenuation of bone metastasis in breast and prostate cancer.
Simultaneously, the collection of articles in this Research Topic splendidly adds novel procedures, attractive targets, and ideas to combat bone metastasis in the milieu of Osteoimmunology. Indeed, this Research Topic will improve our knowledge of bone metastasis and related events in various cancers.