Changes in Indoleamine 2,3-Dioxygenase 1 Expression and CD8+ Tumor-Infiltrating Lymphocytes after Neoadjuvant Chemoradiation Therapy and Prognostic Significance in Esophageal Squamous Cell Carcinoma

Zhu

et al. 2021

Aging

Research on association between programmed cell death ligand 1 (PD-L1) expression in cancer cells and prognosis of esophageal squamous cell carcinoma (ESCC) has been controversial and has focused on patients with surgical resection. We aimed to investigate impact of PD-L1 on treatment response and prognostic value in ESCC and analyze which subset of patients may benefit from immunotherapy. The PD-L1 expression was evaluated by immunohistochemical analysis in all patients. Stratification analysis was performed according to whether surgery was performed. There were no significant correlations between PD-L1 expression with 3-year overall survival (OS) and progression-free survival (PFS) in 81 ESCC patients. Then stratification analysis was performed. Among these 44 patients without surgery, disease control rate (DCR) in negative PD-L1 expression group (78%) was significantly better than those (42%) in positive PD-L1 expression group ( P = 0.032). There were no significant correlations between PD-L1 expression with 3-year OS and PFS in 37 ESCC patients receiving surgery. However, in 44 ESCC patients without surgery, the Kaplan-Meier method showed that 3-year OS and PFS in negative PD-L1 expression group were significantly better than those in positive PD-L1 expression group. In Cox univariate and multivariate model, PD-L1 was an independent prognosticator for inferior OS ( p = 0.011; p = 0.017). Our research revealed prognostic role of PD-L1 expression in cancer cells may be variable in different treatment methods. Consequently, PD-L1 may serve as an independent prognostic factor and provide a theoretical basis for combining conventional therapy with immunotherapy targeting PD-L1 to achieve better treatment outcome in ESCC patients without esophagectomy.

Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Programmed cell death-ligand 1 expression predicts poor treatment response and prognostic value in esophageal squamous cell carcinoma patients without esophagectomy

Zhu

et al. 2021

Aging

“…Finally, cold tumors, also known as non-inflamed tumors, are devoid of TILs. Although no study has identified tumor immune categories in EC, it has been reported that a high density of CD8 cells was significantly correlated with more favorable OS and RFS in patients who received post-CRT (18). Similarly, we found that high levels of TILs induced by CCRT were associated with improved clinical response and survival (19).…”

Section: Icis Required For Escc Treatmentsupporting

confidence: 64%

Immune checkpoint inhibitors for esophageal squamous cell carcinoma: a narrative review

2020

Esophageal cancer (EC) has the seventh highest incidence and the sixth highest mortality rate of any type of cancer worldwide. In China, esophageal squamous cell carcinoma (ESCC) accounts for more than 95% of EC patients. The main treatment for EC patients is surgery and/or chemoradiotherapy (CRT). A large proportion of EC patients are already at an advanced stage of the disease by the time they are diagnosed. In these cases, CRT is left as the only treatment choice, and the treatment outcome is poor. Immune checkpoint inhibitors (ICIs) can improve clinical response and patient survival of patient with many types of tumors through reactivating antitumor immune response. The study of ICIs in ESCC is relative delayed compared with that in other solid tumors. Recent results from clinical trials have demonstrated the safety and efficacy of ICIs either alone or combined with chemotherapy or chemoradiotherapy in ESCC patients. Accumulated evidences also have shown the improved treatment outcome was associated with PD-L1 expression, tumor DNA instability-induced tumor mutational burden (TMB), and drawing lymphocytes into the tumor. Based on these findings, ICIs combined with CRT or radiotherapy (RT) are the focus of ongoing studies. This review will summarize the recent progress in this field, especially the mechanism of ICIs used in ESCC, their clinical efficacy and toxicities, and potential biomarkers.

“…В 23 наблюдениях плоскоклеточного рака пищевода не выявлено влияния ХЛТ на плотность CD8+-T-лим фоцитов [16]. Однако в другом исследовании в 82 случаях при плоскоклеточном раке пищевода плотность этих клеток после ХЛТ повышалась [17]. Увеличение плотности CD8+-T-лимфоцитов выявлено и после ХЛТ немелкоклеточного рака легких [18].…”

Section: Discussionunclassified

Characteristics of composition a lymphoid infiltrate in the tongue squamous cell carcinoma

Zibirov

Мозеров

Полькин

et al. 2022

Opuholi golovy i šei

Introduction. Squamous cell carcinoma of the tongue is the most common oral cancer. The tumor microenvironment has a significant impact on tumor progression; therefore, better understanding of its characteristics is crucial for the treatment strategy, since in some cases it modifies the tumor microenvironment resulting in tumor resistance to therapy.Study objective – to compare the number of CD8+Т-lymphocytes, CD57+NK-cells, and CD20+B-lymphocytes in the microenvironment of tongue squamous cell carcinoma in patients receiving and not receiving neoadjuvant chemoradiotherapy.Materials and methods. We performed immunohistochemical examination of specimens from 67 patients with tongue squamous cell carcinoma who did not receive neoadjuvant chemoradiotherapy. Eleven patients were diagnosed with well differentiated tumors (G1); 21 patients had moderately differentiated tumors (G2); and 35 patients had poorly differentiated tumors (G3). T1 tumors were observed in 11 individuals, T2 tumors – in 26 individuals, T3 tumors – in 26 individuals, and T4 tumors – in 4 individuals. We also examined 30 patients who had undergone neoadjuvant chemoradiotherapy, including external beam radiotherapy (total dose of 60 Gy) and a cycle of polychemotherapy (cisplatin and 5‑fluorouracil). Of them, 6 patients had T1 tumors, 17 patients – T2 tumors, 5 patients – T3 tumors, and 2 patients – T4 tumors. We measured the areas occupied by CD8+T-lymphocytes, CD20+B-lymphocytes, and CD57+NK-cells in the hot spots in the tumor microenvironment.Results. The number of CD8+T-lymphocytes in the tumor microenvironment was higher in patients after neoadjuvant chemoradiotherapy than in those who did not receive it (р = 0.000), whereas the number of CD20+B-lymphocytes was lower after neoadjuvant chemoradiotherapy. The area occupied by CD57+NK-cells in the hot spots of the tumor microenvironment did not differ significantly before and after therapy (p >0.05).Conclusion. Thus, neoadjuvant chemoradiotherapy in patients with tongue squamous cell carcinoma caused an increase in the number of CD8+T-lymphocytes, a decrease in the number of CD20+B-lymphocytes in the tumor microenvironment, and had no effect on the population of CD57+NK-cells.