Head and Neck Cancer
PV QA 2 - Poster Viewing Q&A 2
Purpose/Objective(s): To investigate the influence of proteins involved with tumor immunity on the outcomes of radiation therapy for oropharyngeal squamous cell carcinoma (OPSCC).
Materials/Methods: We performed immunohistochemical staining to examine the expression of p16 and various proteins involved with tumor immunity in 99 OPSCC patients who had undergone definitive radiation therapy between May 2005 and February 2016. PD-L1 expression on tumor cells (TC) and tumor-infiltrating immune cells (IC) was analyzed separately. IC was defined as T cells and macrophages/dendritic cells that infiltrated into tumor cell nests. We scored tumor cells expressing PD-L1 as a percentage of tumor area (tumor cells scored as percentage of PD-L1-expressing tumor cells: TC3≧50%, TC2≧5% and <50%, TC1≧1% and <5%, and TC0<1%; tumor-infiltrating immune cells scored as percentage of tumor area: IC3≧10%, IC2≧5% and <10%, IC1≧1% and <5%, and IC0<1%). PD-L1 positivity was defined as PD-L1 expression on ≧1% of TC and ≧10% on IC. CD8 expression was analyzed tumor-infiltrating cells on a high-power view (X400). We counted manually the number of tumor-infiltrating CD8 positive cells by scoring more than 250 tumor cells (tumor cells scored as percentage of tumor-infiltrating CD8 expressing tumor cells: CD8-score3≧10%, CD8-score2≧5% and <10%, CD8-score1≧1% and <5%, and CD8-score0<1%). CD8 positivity was defined as tumor-infiltrating CD8 expression on ≧5%.
Results: The overall survival rate (OS) and progression-free survival rate (PFS) were both significantly better in the p16-positive group compared with the p16-negative group. Patients with abundant CD8-positive cells infiltrating their tumors had better OS than patients with fewer CD8-positive cells (p = 0.041). Patients with PD-L1-positive tumor cells tended to have a better outcome than those with PD-L1-negative tumor cells for both OS (p = 0.067) and PFS (p = 0.066). Patients with high PD-L1 expression in infiltrating immune cells (IC 3) showed significantly better OS (p = 0.004) and PFS (p = 0.005) than those with low PD-L1 expression in immune cells (IC 0, 1, and 2). Patients with p16-positive tumors and IC 3 had significantly better OS than the other groups (p16-negative and/or IC 0, 1, and 2), while patients with p16-negative tumors and IC 3 showed similar OS to patients with p16-positive tumors and IC 0–2. Compared with p16-negative tumors, p16-positive tumors had a significantly higher frequency of CD8-positive cell infiltration, as well as a significantly higher frequency of PD-L1 expression in tumor cells and infiltrating immune cells. In multivariate analysis, age and PD-L1-positive infiltrating immune cells were associated with OS, but p16 status was not. On the other hand, p16 status and PD-L1-positive infiltrating immune cells were significantly associated with PFS.
Conclusion: In addition to p16 expression, PD-L1-positive infiltrating immune cells can be useful for predicting the response of OPSCC to radiation therapy.
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