A four‐factor immune risk score signature predicts the clinical outcome of patients with spinal chordoma

Abstract

Background Currently, the measurement of immune cells in previous studies is usually subjective, and no immune‐based prognostic model has been established for chordoma. In this study, we sought to simultaneously measure tumor‐infiltrating lymphocyte (TIL) subtypes in chordoma samples using an objective method and develop an immune risk score (IRS) model for survival prediction. Methods Multiplexed quantitative immunofluorescence staining was used to determine the TIL levels in the tumoral and stromal subareas of 114 spinal chordoma specimens (54 in the training and 60 in the validation cohort) for programmed death‐1 (PD‐1), CD3, CD8, CD20 (where CD is cluster of differentiation), and FOXP3. Flow cytometry was performed to validate the immunofluorescence assay for lymphocyte measurement on an additional five fresh chordoma specimens. Subsequently, the IRS model was built using the least absolute shrinkage and selection operator (LASSO) Cox regression method. Results Flow cytometry and quantitative immunofluorescence showed similar lymphocytic percentages and TIL subpopulation proportions in the fresh tumor specimens. With the training data, the LASSO model identified four immune features for IRS construction: tumoralFOXP3, tumoralPD‐1, stromalFOXP3, and stromalCD8. In both cohorts, a high IRS was significantly associated with tumoral programmed cell death‐1 ligand 1 expression, Enneking inappropriate tumor resection, and surrounding muscle invasion by tumor. Multivariate Cox regression and stratified analysis in the two cohorts revealed that the IRS was an independent predictor and could effectively separate patients with similar Enneking staging into different risk subgroups, with significantly different survival rates. Further receiver operating characteristic analysis found that the IRS classifier had a better prognostic value than the traditional clinicopathological factors and compensated for the deficiency of Enneking staging for outcome prediction. More importantly, a nomogram based on the IRS and clinical predictors showed adequate performance in estimating disease recurrence and survival of patients. Conclusions These data support the use of the IRS signature as a reliable prognostic tool in spinal chordoma and may facilitate individualized therapy decision making for patients.

Clinical Implication of Systemic Immune-Inflammation Index and Prognostic Nutritional Index in Skull Base Chordoma Patients

“…Cox proportional regression hazard models were used to identify potential independent prognostic variables, and factors significant in univariable analysis were enrolled in the multivariable analysis. The bootstrap resample analysis with 1,000 repeats (24), which was widely used to test the reproducibility of survival data via randomly sampling patients from the same cohort, was performed to validate our results (25)(26)(27). Receiver operating characteristic (ROC) curve analysis was applied to evaluate the prognostic capacity of these inflammatory markers for 3-year and 5-year OS.…”

Immunotherapy for Chordoma and Chondrosarcoma: Current Evidence

“…Chordomas have extensive interactions with the immune system that may help to predict tumor aggressiveness, responses to existing therapies and the development of novel treatments ( Figure 1 ). Zou and colleagues have studied this interaction extensively, specifically in regard to the PD-1/PDL-1 pathway [ 18 , 19 , 20 , 21 ]. In their initial investigations, they reported that the expression of PD-L1 in tumor tissue was associated with advanced chordoma stages and higher levels of tumor-infiltrating lymphocytes (TIL), whereas PD-L1 expression on TIL was associated with improved local recurrence free survival (LRFS) and overall survival [ 18 , 19 ].…”

“…A few authors have proposed immune-based scoring systems for chordomas to help to predict tumor aggressiveness and outcomes [ 19 , 21 , 26 ]. One study found that in their proposed scoring system of cells by levels of CD3 + and CD8 + TIL in the tumor interior, higher levels of TILs were associated with increased LRFS and overall survival [ 18 ].…”

Development and Validation of a 6-miRNA Prognostic Signature in Spinal Chordoma

“…These patients received curative tumor excision and follow-up information was updated in April 2019. Patients selection fulfilled comparable baseline, treatment and follow-up characteristics to that of the training population (Supplementary Table 1) (22). Sample size in validation group was estimated in advance by a power calculation (23), and minimum of 45 patients were required to show difference with a power of 80%, b error of 0.2, and a error of 0.05.…”

“…A total of 114 patients (54 in the training and 60 in the validation cohort) were included. Patient characteristics were recently communicated by our group (22) Table 1). All chordoma cases belonged to classic pathology type.…”