AimsLimited information is available regarding the precise differences in the tumour immune microenvironment (TIM) of patients with human papilloma virus (HPV)-associated and non-HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Here, we retrospectively reviewed 137 patients with OPSCC treated with a definitive treatment to identify molecular relationships in the TIM.Materials and methodsWe used immunohistochemical analysis to assess p16 status, programmed death ligand 1 (PD-L1) level, and/or CD8+ tumour-infiltrating lymphocyte (TIL) density, followed by prognostic evaluation of these immune-related parameters.ResultsMultivariate analyses demonstrated that PD-L1 level on immune cells but not on tumour cells or CD8+ TIL density was a significant predictive factor of disease-free survival (DFS) and overall survival (OS). Additionally, subgroup analyses demonstrated that patients positive for p16 and PD-L1 expression on immune cells had favourable DFS and OS, whereas patients negative for p16 and PD-L1 expression on immune cells showed worse DFS and OS.ConclusionsWe demonstrated that PD-L1 expression on immune cells but not tumour cells might represent a useful prognostic biomarker in patients with OPSCC receiving a definitive treatment. We propose that a co-assessment of p16 and PD-L1 expression on immune cells would have greater prognostic potential compared with evaluation of each factor alone in patients with OPSCC.
Objective Limited information is available regarding the role of programmed death ligand 1 (PD‐L1) expression and CD8+ tumor‐infiltrating lymphocyte (TIL) density in the tumor immune microenvironment (TIM) of patients with salivary gland carcinoma (SGC). This study aimed to assess the association between the prognosis of SGC patients and the probability of PD‐L1 expression in tumor and/or immune cells using the tumor proportion score (TPS), mononuclear immune cell density score (MIDS), combined positive score (CPS), and CD8+TIL density in the TIM. Study Design Retrospective cohort study. Methods We retrospectively reviewed 73 SGC patients treated with definitive surgery between 2000 and 2015. Immunohistochemical analysis was used to assess TPS, MIDS, CPS, and CD8+TIL density, followed by prognostic evaluation of these immune‐related parameters. Results Histological grade was associated with TPS, MIDS, and CPS based on PD‐L1 expression, and these scores exhibited a significant association with CD8+TIL density. Patients with positive TPS had an unfavorable disease‐free survival and overall survival. Multivariate analyses indicated that the TPS was a significant and independent prognostic factor. Conclusion Our results suggest that TPS might be a useful prognostic biomarker in SGC patients receiving definitive surgery. Laryngoscope, 131:E1481–E1488, 2021
Visible photoluminescence from oxidized Si microcrystalline particles was observed under excitation of an He-Cd laser at room temperature. The particles had been prepared by mean of the SiH4 gas breakdown method with a Nd3+-YAG pulse laser. The particles formed a single-crystalline structure of Si. The photoluminescence spectrum obtained from these particles showed maximum intensity at a wavelength of 730 nm. This wavelength did not change with particle size. These Si particles exhibited visible photoluminescence when oxidized.
ObjectivesLimited information exists regarding the associations between pre‐existing immune parameters in the tumor immune microenvironment (TIM) and either chemoradiosensitivity or prognosis for patients with squamous cell carcinoma of the nasopharynx or oropharynx involving virus‐related or nonvirus‐related tumors.Study DesignRetrospective cohort study.MethodsWe retrospectively reviewed 141 patients with EBV+, p16+, or EBV− and p16− statuses who are receiving chemoradiotherapy. We performed immunohistochemistry using pretreatment biopsy specimens to analyze the programed death ligand 1 (PD‐L1) levels in tumor and immune cells and CD8+ tumor‐infiltrating lymphocyte (TIL) density. We evaluated chemoradiosensitivity and prognosis with respect to these immune‐related parameters.ResultsVirus‐related tumors showed associations with both PD‐L1 expression and high CD8+ TIL density. Patients with higher CD8+ TIL density or greater numbers of PD‐L1+ tumor and immune cells showed significant rates of favorable local recurrence‐free survival (LRFS), progression‐free survival (PFS), and overall survival (OS). Multivariate analyses demonstrated that higher CD8+ TIL density is an independent, significant, and favorable predictive factor for LRFS (P = .005) and OS (P = .003), although it is not a significant predictor of PFS (P = .077).ConclusionsHigher CD8+ TIL density represents a useful and favorable biomarker of chemoradiosensitivity in patients receiving chemoradiotherapy for nasopharyngeal or oropharyngeal cancer.Level of Evidence3 Laryngoscope, 131:E1179–E1189, 2021
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. Immune checkpoint inhibitors (ICI) are utilized in systemic therapies that induce T cells to specifically target and kill tumor cells 1. Programmed death 1 (PD-1) is a receptor expressed on the T cell membrane, which binds to programmed death-ligand 1 (PD-L1) on tumor cells, resulting in T cell anergy and inhibition of antitumor activity 2. In the case of squamous cell carcinoma of the head and neck (SCCHN), the "CheckMate 141" phase 3 trial demonstrated that nivolumab therapy, which inhibits the PD-l/PD-L1 and PD-L2 axis, increases the survival periods of people with recurrent/metastatic SCCHN (RMSCCHN) compared to the therapy selected by investigators 3. 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. Radiation therapy (RT) or chemo-radiation therapy (CRT) is now a standard procedure for patients with head and neck cancer 5. Recent studies have shown that PD-L1 expression changed in response to chemotherapy (CT), RT, and molecular target therapy 6-8. RT is known to induce cancer cell death and has positive immunemodulatory abilities, including causing the increased expression of MHC-class I molecules, releasing various tumor antigens, and accumulating tumor-infiltrating lymphocytes (TILs) 9-11. Furthermore, a recent study showed that tumor cell PD-L1 expression is upregulated in response to IFN-gamma, produced by CD8+ T cells, through
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