Prognostic value of immune score in nasopharyngeal carcinoma using digital pathology

Abstract

BackgroundTumor-infiltrating lymphocytes have been reported as prognostic markers in tumors. We aimed to assess the prognostic value of total T cell (CD3+) density, cytotoxic T cell (CD8+) density and memory T cell (CD45RO+) density in patients with nasopharyngeal carcinoma (NPC).MethodsThe expression of CD3, CD8 and CD45RO was detected by immunohistochemistry in the training (n=221) and validation cohorts (n=115). The densities of these three markers were quantified by digital pathology both in the tumor and stroma. Then, we developed the immune score based on the density of these three markers and further analyzed its prognostic value.ResultsThe high density of CD3+, CD8+ and CD45RO+ T cells both in the tumor and/or stroma were significantly associated with the decrease in mortality in the training cohort, respectively. High immune score predicted a prolonged overall survival (OS) (HR 0.34, 95% CI 0.18 to 0.64, p=0.001, disease-free survival (DFS) (HR 0.44, 95% CI 0.25 to 0.78, p=0.005) and distant metastasis-free survival (DMFS) (HR 0.43, 95% CI 0.21 to 0.87, p=0.018) in NPC patients. The findings were confirmed in the validation cohort. Multivariate analysis revealed that immune score remained an independent prognostic indicator for OS, DFS and DMFS. In addition, we established a nomogram with the integration of all independent variables to predict individual risk of death.ConclusionsWe established an immune score model, which provides a reliable estimate of the risk of death, disease progress and distant metastasis in NPC patients.

Prognostic Value of Tumor Infiltrating Lymphocytes in Nasopharyngeal Carcinoma Patients: Meta-Analysis

“…However, in subgroup analysis, CD8+ cells infiltrated in the intratumoral site showed significantly improved OS (HR = 0.31; 95%CI = 0.16-0.62; P = 0.001) ( Figure 6 ). Because only one study, Wang et al , 20 reported on the association of CD8+ stromal TILs with OS, we did not perform meta-analysis on this subgroup.…”

“…Fourteen studies 5,[18][19][20][21][22][23][24][25][26][27][28][29][30] were pooled and evaluated for analysis of TILs lymphocytes for OS and DFS in NPC patients. Wang et al 24 have analyzed a large cohort and validated it with an independent cohort focusing on the total intensity of TILs, however most the rest of the studies focused on a set of phenotypic subtypes of immune cells (including CD3, CD4, CD8, regulatory T cells and macrophages).…”

Metavariables Resuming Host Immune Features and Nodal Involvement Are Associated with Oncological Outcomes in Oral Cavity Squamous Cell Carcinoma

“…Although limited to few studies, an association between high tumor CD8 + T-cell density and a better distant metastasis free-survival was already observed in solid tumors from different primary sites including breast [ 46 ], colon [ 47 ] or soft tissues [ 48 ]. Among head and neck malignancies, evidence derived from the analysis of nasopharyngeal carcinoma [ 49 ], hypopharyngeal carcinoma [ 50 , 51 ] or from carcinomas of mixed primary sites [ 52 ] further support this finding. For OSCC, the association of CD8 + T-cell infiltration and distant failure still needs to be better defined [ 53 ]; however, indirect but still limited findings [ 52 ], support their protective role.…”

The role of multiple metabolic genes in predicting the overall survival of colorectal cancer: A study based on TCGA and GEO databases

“…On the basis of the multivariate COX regression model, each gene in the model is listed on a flat diagram by using a scaled line segment according to a certain scale. Then, each gene is scored and the scores of all genes are added to obtain a total score, which is used to predict the survival and prognosis of CRC patients [ 23 ]. The nomogram is drawn using the "rms" package of R software.…”