Abstract
Squamous cell carcinoma of the head and neck (SCCHN) has a high recurrence rate after (chemo) radiation therapy [(C)RT]. The relationship between the changing levels of immune checkpoint molecules and immune cells in pre-(C)RT tissues and locally recurrent tissues in the irradiated field, after (C)RT completion, is not known. This study aimed to assess the changes in these immune parameters between pre-(C)RT tissue and the same area after local recurrence post-(C)RT. We retrospectively reviewed 30 (C)RT-treated patients with SCCHN. We performed immunohistochemical analyses on these immune parameters using paired tissue samples obtained pre-(C)RT and at local recurrence sites post-(C)RT. No significant changes in immune parameters were found between the pre-(C)RT and locally recurrent tissues. An increased density of CD8+ tumor-infiltrating lymphocytes (TILs) showed a significantly positive correlation with PD-L expression on tumor cells (TC-PD-L1). Patients with increased TC-PD-L1 expression and CD8+TIL density showed favourable prognosis, and one of them showed a favourable response to nivolumab therapy. Our study shows a positive association between TC-PD-L1 upregulation and increased CD8+TIL density, and demonstrates that patients with these changes have a favourable survival outcome.
Highlights
Immune checkpoint inhibitors (ICI) are utilized in systemic therapies that induce T cells to target and kill tumor cells[1]
A recent study reported that radiation-induced immune responses led to programmed death-ligand 1 (PD-L1) upregulation and increased dendritic and cytotoxic T cell activation and p roliferation[16]
We investigated the association between changes in immune parameters, including PD-L1 using pre-(C)Radiation therapy (RT) and locally recurrent paired tissue samples
Summary
Immune checkpoint inhibitors (ICI) are utilized in systemic therapies that induce T cells to target and kill tumor cells[1]. The expression levels of PD-L1 on tumor and immune cells is a known predictive biomarker that correlates with the efficacy of PD-1/PD-L1 inhibitors[4]. This correlation was confirmed in a recent analysis of 2-year long-term survival data from CheckMate 141, showing that nivolumab therapy results in favourable overall survival (OS) and OS benefits in patients with PD-L1 expression ≥ 1%4. Several studies have reported changes in the immune checkpoint molecule expression levels that correlate with immune cell levels between the tissue samples obtained at pre-treatment sites and sequentially surgically resected tissue after neoadjuvant CT or CRT7 ,13,14. Lim et al.[14] reported that patients with oesophageal cancer receiving neoadjuvant chemo-radiotherapy displayed a significant increase in PD-L1 expression between pre-CRT and post-CRT evaluations, in 12 paired tissue samples
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