A Stumbling Block in immunity evaluation and Immunotherapy for Musculoskeletal Tumors

Musculoskeletal tumors are a highly heterogeneous group of rare tumors with complex histological subtypes and are usually characterized by poor prognosis and limited therapeutic options in the advanced setting. Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) axes have shown efficacy in a variety of tumor types and have been explored as a possible therapeutic strategy for musculoskeletal tumors in various settings. One hallmark of immunotherapy is the long duration of the response, which is likely due to memory of the adaptive immune system, which translates into long-term survival for a proportion of patients. Unfortunately, immune checkpoint inhibitors have shown promising efficacy only in patients with limited specific subtypes of musculoskeletal tumors. Available evidence suggests that baseline PD-L1 expression, tumor mutation concordance, and microsatellite instability may not be strong predictive biomarkers in unselected patients. Modification of the suppressive immune microenvironment, such as targeting tumor-associated macrophages, cancer-associated fibroblasts, dendritic cells, etc., may be able to improve limited responses. Therefore, reasonable assessment before treatment and in-depth exploration of resistance mechanisms are essential.

In this research topic, we hope to address the ongoing challenges associated with pre-immunotherapy assessment and limited response to immunotherapy in musculoskeletal tumors.

We welcome submissions, but not limited to the following topics:
- Novel immunotherapeutic targets and drugs against musculoskeletal tumors.
- Potential biomarkers of diagnostic, therapeutic, and prognostic value for pre-immunotherapy evaluation.
- Pre-clinical or clinical studies related to immunotherapy for musculoskeletal tumors.
- Emerging findings inducing resistance to immunotherapy in musculoskeletal tumors.
- Targeting the tumor microenvironment to improve immunotherapy responses in musculoskeletal tumors.

Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope of this section and will not be accepted as part of this Research Topic.