journal contribution
posted on 2023-04-01, 00:00 authored by Wei Shi, Mackenzie Fijardo, Jeff P. Bruce, Jie Su, Wei Xu, Rachel Bell, Pierre-Antoine Bissey, Angela B.Y. Hui, John Waldron, Trevor J. Pugh, Kenneth W. Yip, Fei-Fei Liu Table S1: Patient Radiotherapy Information and Multivariate Analysis.
Figure S1: Workflow of evaluation of T cell receptor (TCR) rearrangement and ESTIMATE immune score from RNA-sequencing data, and the expression of tumor-infiltrating lymphocytes (TILs) in NPC patients.
Figure S2: The correlation of ESTIMATE immune score with rearranged TCR reads and CD8+ TILs.
Figure S3: The correlation of CIBERSORT and TIMER 2.0 with rearranged TCR reads and CD8+ TILs.
Figure S4: The distribution of TILs in NPC samples.
Figure S5: Clinical impact of CD8+ TILs in the combined cohort of NPC patients.
Funding
Canadian Institutes of Health Research (IRSC)
Canadian Cancer Society (CCS)
The Peter and Shelagh Godsoe Chair in Radiation Medicine
The University of Toronto Faculty of Medicine
Princess Margaret Cancer Centre
The Princess Margaret Cancer Foundation
The Ontario Ministry of Health
History
ARTICLE ABSTRACT
Tumor-infiltrating lymphocytes (TIL) are immune cell populations found within tumors, critical in the antigen-specific host immune response. In this study, we aimed to elucidate the prognostic significance of CD3+, CD4+, and CD8+ TILs in nasopharyngeal cancer (NPC).
Immune cell infiltration was quantified in NPC samples (n = 50) using RNA-sequencing (RNA-seq) data based on rearranged T-cell receptor (TCR) reads and the Estimation of Stromal and Immune cells in malignant tumors using expression data (ESTIMATE) immune score tool. The differential abundances of TIL subset populations were also characterized through IHC staining of formalin-fixed, paraffin-embedded samples from a training cohort (n = 35), which was a subset of the RNA-seq cohort (n = 50).
In the RNA-seq cohort, patients with higher rearranged TCR reads experienced superior 5- and 10-year overall survival (OS; P < 0.001), and disease-free survival (DFS; P < 0.001). Similarly, patients with higher ESTIMATE immune scores experienced superior 5- and 10-year OS (P = 0.024) and DFS (P = 0.007). In the training cohort, high abundances of CD8+ TILs were significantly associated with improved 5- and 10-year OS (P = 0.003) and DFS (P = 0.005). These findings were corroborated in an independent validation cohort (n = 84), and combined analysis of the training and validation cohorts [n = 119 (35+84)], which further demonstrated improved 5- and 10-year survival in terms of locoregional control (P < 0.001) and distant metastasis (P = 0.03).
Taken together, our study highlights the prognostic value of CD8+ TILs in NPC, and the potential of future investigations into cellular-based immunotherapies employing CD8+ lymphocytes.
