Hao Jiang

Emerging evidence highlights the pivotal role of KISS1 in cancer metastasis; however, there remains a dearth of pancancer analyses, particularly concerning immunotherapy. Here, we conducted a comprehensive investigation of KISS1 across various cancers, with a specific focus on breast cancer, using TCGA and GTEx datasets. We observed a tissue context‐dependent role function of KISS1 in tumor metastasis, which exhibited suppressive effects in various tumors but promoted the metastatic phenotype in breast cancer. Our study revealed a noteworthy disparity between KISS1 expression at the mRNA and protein levels, indicating potential posttranslational modifications within cancer cells. Moreover, KISS1 is significantly associated with immune cell infiltration and immunosuppressive cells, suggesting its crucial role in modulating tumor immunotherapy. Intriguingly, our investigation also elucidated KISS1’s involvement in promoting breast cancer metastasis, thereby providing valuable insights into the molecular underpinnings of this process. Furthermore, we validated the presence of posttranslational modifications of KISS1 in breast cancer, adding to our understanding of its role in tumorigenesis. By shedding light on the tissue context‐dependent function of KISS1 and its implications for immunotherapy, our pancancer study offers novel perspectives on the oncogenic roles of KISS1 and provides potential avenues for the development of targeted therapies and diagnostic biomarkers.

Osteosarcoma (OS) is a lethal malignant orthotopic bone tumor that primarily affects children and adolescents. Biomimetic nanocarriers have attracted wide attention as a new strategy for delivering chemotherapy agents to the OS. However, challenges such as rapid clearance and limited targeting hinder the effectiveness of OS chemotherapy. In this study, we designed reactive oxygen species (ROS)-responsive nanoparticles (NPs) coated with an interleukin (IL)11-engineered macrophage membrane (MM). The camouflage by MMs prevents clearance of IL-11-engineered MM-coated NPs loaded with doxorubicin (IL-11/MM@NPs/Dox) by the immune system. Moreover, the macrophage membrane combined with surface-expressed IL-11 not only directed IL-11/MM@NPs/Dox to OS tissues but also selectively identified IL-11 receptor alpha (IL-11Rα)-enriched OS cells. Within these cells, elevated levels of ROS triggered the controlled release of Dox from the ROS-responsive NPs. The synergistic modification of targeted ligand conjugation and cell membrane coating on the ROS-responsive NPs enhanced drug availability and reduced toxic side effects, thereby boosting the efficacy of OS chemotherapy. In summary, our findings suggest that IL-11/MM@NPs/Dox represents a promising approach to improving OS chemotherapy efficacy while ensuring excellent biocompatibility.

The tumor microenvironment (TME) acts as a crucial role in the occurrence and development of osteosarcoma (OS). Despite this, the mechanism controlling the components of immunity and stroma in the tumor microenvironment remains a mystery. To conduct this study, we download and collate transcriptome data from the TARGET database, whose full name is Therapeutically Applicable Research to Generate Effective Treatments, as well as available clinical information of OS. The CIBERSORT and ESTIMATE methodology are used to acquire the proportions of components of immunity and stroma and tumor-infiltrating immune cells (TICs). Protein-protein interaction (PPI) networks and Cox regression analysis are used to select differentially expressed genes (DEGs). A prognostic biomarker is determined by intersecting univariate COX and PPI results, which lead to the finding of Triggering receptor expressed on myeloid cells-2 (TREM2). Based on the next analysis, TREM2 expression is positively correlated with OS survival time. Immune function-related genes have enrichment in the group with high expression of TREM2, according to gene set enrichment analysis (GSEA). The percentage of TICs by CIBERSORT methodology revealed that the expression of TREM2 is positively associated with follicular helper T cells, CD8-positive T cells, and M2 macrophages and negatively correlated with plasma cells, M0 macrophages, and naive CD4-positive T cells. All results suggest a possible integral role of TREM2 in the immune-related events of TME. Therefore, TREM2 may be a potential indicator of remodeling of TME in osteosarcoma, which is useful and helpful in predicting the clinical prognostic outcome of OS patients and provide a unique perspective for immunotherapy for OS.