Tumor infiltrating immune cells (TIICs) as a biomarker for prognosis benefits in patients with osteosarcoma

Abstract

Background Osteosarcoma is a rare malignant bone tumor in adolescents and children. Poor prognosis has always been a difficult problem for patients with osteosarcoma. Recent studies have shown that tumor infiltrating immune cells (TIICs) are associated with the clinical outcome of osteosarcoma patients. The aim of our research was to construct a risk score model based on TIICs to predict the prognosis of patients with osteosarcoma. Methods CIBERSORTX algorithm was used to calculate the proportion of 22 TIIC types in osteosarcoma samples. Kaplan-Meier curves were drawn to investigate the prognostic value of 22 TIIC types. Forward stepwise approach was used to screen a minimal set of immune cell types. Multivariate Cox PHR analysis was performed to construct an immune risk score model. Results Osteosarcoma samples with CIBERSORTX output p value less than 0.05 were selected for research. Kaplan-Meier curves indicated that naive B cells (p = 0.047) and Monocytes (p = 0.03) in osteosarcoma are associated with poor prognosis. An immune risk score model was constructed base on eight immune cell types, and the ROC curve showed that the immune risk score model is reliable in predicting the prognosis of patients with osteosarcoma (AUC = 0.724). Besides, a nomogram model base on eight immune cell types was constructed to predict the survival rate of patients with osteosarcoma. Conclusions TIICs are closely related to the prognosis of osteosarcoma. The immune risk score model based on TIICs is reliable in predicting the prognosis of osteosarcoma.

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“…Gomez-Brouchet et al found that CD8 T cells were related to the non-metastatic osteosarcoma [88], and higher infiltration rate of CD8 T cells indicated improved survival outcome [89], showing consistency with our result that the low-risk osteosarcoma patients with superior prognosis had higher infiltration proportion of CD8 T cells. In terms of activated dendritic cells, Wang et al demonstrated that activated dendritic cell was an independent predictor of osteosarcoma and the model basing on several immune cell types including activated dendritic cell could reliably predict the prognosis of osteosarcoma patients [90], suggesting the potentially important role of activated dendritic cells in osteosarcoma. However, the specific functions of these significantly distinct infiltrating immune cells between the osteosarcoma patients with high and low risk scores and the underlying mechanism still need further research.…”

The Role of Inflammation in Breast and Prostate Cancer Metastasis to Bone

“…Another hint was the identification of similar inflammatory and tissue remodeling mechanisms that are shared between tumor stroma formation and wound healing processes, which have led to the concept that tumors are “wounds that do not heal” [ 11 , 12 ]. It is now well-established that tumor-infiltrating immune cells can predict survival and therapeutic outcomes in several malignancies such as osteosarcoma, colorectal, or breast cancer (BrCa) [ 13 , 14 , 15 , 16 ]. An additional level of complexity is added by the presence of other resident cells and structures within the tumor microenvironment (TME), which are not silent bystanders but are rather fostered (or at least affected) by inflammatory mechanisms, including tumor-associated macrophages (TAM) [ 17 ], cancer-associated fibroblasts (CAFs) [ 18 ], mesenchymal stromal cells [ 19 ], adipocytes [ 20 ], and endothelial cells [ 21 ].…”