The current advances and future directions of PD-1/PD-L1 blockade in head and neck squamous cell carcinoma (HNSCC) in the era of immunotherapy.

Immune checkpoint inhibitors (ICIs) have previously demonstrated their efficacy and safety in various solid tumors, and with the growing interest in the application of ICIs in head and neck squamous cell carcinoma (HNSCC), various data have been reported. Mechanistically, HNSCC cells express programmed death ligand 1 (PD-L1), which binds to its receptor programmed death 1 (PD-1). Immune escape plays a key role in disease initiation and progression. Studying the abnormal activation of related pathways of PD-1/PD-L1 will help to understand the way of immunotherapy and find the advantageous population of immunotherapy. How to reduce HNSCC-related mortality and morbidity in this process has promoted the search for new therapeutic strategies, especially in the era of immunotherapy. PD-1 inhibitors have demonstrated significant prolongation of survival in recurrent/metastatic (R/M) HNSCC with a favorable safety profile. It also holds great promise in locally advanced (LA) HNSCC, where numerous studies are underway. Although immunotherapy has made great progress in HNSCC research, there are still many challenges. Therefore, in the review, we conducted an in-depth study on the expression of PD-L1 and the regulatory, immunosuppressive mechanisms caused by PD-L1, especially in head and neck squamous cell carcinoma, which is different from other tumors. And further summarize the situation, challenges and development trends of PD-1 and PD-L1 blockade in clinical practice.

PD-L1 in Combination with CD8+TIL and HIF-1α are Promising Prognosis Predictors of Head and Neck Squamous Cell Carcinoma.

OBJECTIVE: The aim of this study was to evaluate the prognosis effect of PD-L1 in combination with CD8+ tumor-infiltrating lymphocyte (TIL) or HIF-1α in head and neck squamous cell carcinoma (HNSCC). METHODS: A total of 63 patients who underwent surgical resection were included in this study. The level of PD-L1, CD8+ TIL, and HIF-1α was determined by immunohistochemical analysis. The survival of patients was evaluated by Kaplan-Meier analysis. The prognostic power of these parameters was evaluated by C-index. RESULTS: We observed that the survival of patients, who had a high level of PD-L1 in tumor cells, was significantly shorter than those who had a low level of PD-L1. However, the survival of patients who had a high level of PD-L1 in tumor microenvironment was significantly longer than patients with a low level of PD-L1 in tumor microenvironment. In addition, high level of CD8+ tumor-infiltrating lymphocyte or low level of HIF-1α level suggests a better prognosis. Moreover, we observed that PD-L1 in combination with CD8+ tumor-infiltrating lymphocyte and HIF-1α could significantly improve the prognostic effect of current TNM stage. CONCLUSION: The results of this study suggest that the level of PD-L1, CD8+TIL, and HIF-1α are useful prognostic biomarkers for patients with HNSCC. Incorporating these biomarkers into current TNM stage of HNSCC improve the discriminatory capability of TNM stage.

Plasma levels of soluble programmed death ligand 1 (sPD-L1) in WHO II/III nasopharyngeal carcinoma (NPC): A preliminary study.

Plasma levels of soluble PD-L1 (sPD-L1) have been reported to be an independent prognostic factor in many malignant tumors. The expression of sPD-L1 in nasopharyngeal carcinoma (NPC) has not been reported. The purpose of this study was to evaluate the expression of sPD-L1 and analyze its correlation with clinical characteristics in patients with NPC.Thirty-five patients with stage I-IVa NPC were included. Plasma samples were obtained pretreatment. The sPD-L1 concentrations were measured by enzyme-linked immunosorbent assay (ELISA). The correlations of sPD-L1 expression with clinical parameters and laboratory data were analyzed.sPD-L1 was detected in 35 plasma samples, the mean sPD-L1 concentration was 45.47 pg/ml. sPD-L1 was significantly higher in stage III-IVa (50.76 ±â€Š28.15 pg/ml) compared to stage I-II (19.87 ±â€Š11.38 pg/ml) (t = 2.618, P = .013). sPD-L1 was also higher in stage N2-3 (52.03 ±â€Š28.98 pg/ml) than that in N0-1 (32.88 ±â€Š23.75 pg/ml) (t = 2.096, P = .046). Univariate analysis identified that sPD-L1 level positively correlated with clinical stage (r = 0.495, P = .002) and N stage (r = 0.34, P = .046). Multivariate analysis showed the clinical stage was an independent factor affecting sPD-L1 expression.This is the first report to detect sPD-L1 in NPC. The study indicated sPD-L1 is quantifiable, convenient and easy to obtain. sPD-L1 may serve as a useful biomarker for evaluating tumor progression and therapeutic efficacy of NPC.

Ten-Year Outcomes Of Intensity-Modulated Radiotherapy (IMRT) Combine With Chemotherapy Versus IMRT Alone For Stage II Nasopharyngeal Carcinoma In The Real-World Study (RWD).

OBJECTIVES: The aim was to define the role of chemotherapy in stage II nasopharyngeal carcinoma (NPC) and to identify the toxicity of chemotherapy for these patients in the era of intensity-modulated radiotherapy (IMRT). METHODS: Between January 2002 and December 2013, 169 patients with stage II NPC were analyzed. Of these patients, 149 patients treated with chemotherapy were divided into three groups as follows: neoadjuvant chemotherapy followed by IMRT (NCT) group, concurrent chemotherapy with IMRT (CCRT) group, and neoadjuvant chemotherapy followed by CCRT (NC+CCRT) group. In addition, 20 patients received IMRT alone. We retrospectively assessed the 10-year survival and acute adverse effects in the patients using SPSS software. RESULTS: The median follow-up time was 93 months (2-160 months). The 10-year OS of the NCT, CCRT, NC+CCRT groups vs the IMRT alone group was 69.8%, 63.4%, 69.7% vs 72.4%, respectively (P=0.664, 0.940, and 0.998, respectively). Both univariable and multivariable analyses showed that the addition of chemotherapy to IMRT did not significantly improve the 10-year survival outcomes. The hematotoxicity and mucous reaction of patients with chemotherapy were more serious than those with IMRT alone (P=0.007 and 0.049). Distant metastasis for stage II NPC patients mostly occurred within 3 years, which is very different from patients with advanced NPC. CONCLUSION: Patients with stage II NPC who are treated with IMRT may obtain satisfactory long-term survival outcomes. The additional chemotherapy cannot significantly increase survival; however, it may remarkably increase treatment-associated acute toxic reactions.