B lymphocytes exert multifaceted functions to produce antibodies in humoral response, present antigen in cell-mediated immunity and suppress immunopathology via anti-inflammatory cytokines. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancers in world. The development and progression of HNSCC is closely related to the dysregulation and evasion of immune system, which enables cancer cells to proliferate and metastasize. In HNSCC, high CD8+ T cell infiltration predicts better patient survival, and the suppressive T cells (Treg) correlates with tumor progression. Nevertheless, the precise role of tumor-infiltrating B lymphocytes (TIL-B) in HNSCC is poorly defined.
With a recently published bioinformatics approach, Tumor Immune Estimation Resources (TIMER), comprehensive pan-Cancer analysis was performed on 25 cancer types using the publicly available TCGA database with both survival and RNA-Seq information. Univariate COX regression demonstrates that in lower grade glioma (Hazard Ratio (HR)=830, P=1.3E-06), diffuse large B-cell lymphoma (HR=130, P=0.01), and papillary renal cell carcinoma (HR=15, P=0.02), TIL-B levels are associated with poor survival. Whilst in HNSCC (HR=0.082, P=0.0015), breast invasive carcinoma (HR=0.12, P=0.042), uterine corpus endometrial carcinoma (HR=0.045, P=0.039), cervical carcinoma (HR=0.00049, P=0.022,) and thymoma (HR=1.6E-05, P=0.026), TIL-B levels are associated with better survival. Note that among these 5 cancer types, HNSCC has the lowest P-value, suggesting TIL-B level is likely a good prognostic biomarker for patient outcome in HNSCC. In other 17 cancer types, TIL-B are not related to patient survival (P=n.s.).
In HNSCC, clinicopathological analysis shows that the extreme high TIL-B level (top 15% patients with the highest TIL-B level vs. the bottom 15%) is associated with living status (P=0.0047), early AJCC pathological T stage (P=2.71E-04), high differentiation grade (P=5.00E-05), and the absence of perineural invasion (P=8.52E-04). Furthermore, Kaplan-Meier survival curves based on TIL-B level indicate that patients with high TIL-B (top 15%) show longer survival compared with those with low level (bottom 15%; P=0.0005). The median overall survival time is 67.81 months in TIL-B high and 35.91 in TIL-B low group.
In conclusion, this study reveals that TIL-B may serve as independent prognostic biomarker for overall survival of HNSCC patients.
Acknowledgements:
VWYL receives funding supports from the Research Grant Council, HK (General Research Fund: #1711484; #17121616; #14168571; Theme-based Research: T12-401/13-R), Health and Medical Research Fund (HMRF #15160691), the University-Industry Collaboration Program (UIM/329; Innovation and Technology Fund, HK), and the Hong Kong Cancer Fund, HK.
YL receives funding (Postdoctoral Hub of UIM/329) from the Innovation and Technology Fund, HK government)
This study also receives funding from Lee Hysan Foundation Research Grant & Endowment Fund Research Grant Schemes 2018-2019.
Citation Format: Yuchen LIU, Vivain W. Lui. Tumor-infiltrating B lymphocytes may serve as a prognostic biomarker for head and neck squamous carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4249.
