ABSTRACT
Objective:To explore the levels of programmed death receptor 1 (PD-1) and lymphocyte activating gene 3 (LAG-3) in the immune microenvironment of diffuse large B-cell lymphoma (DLBCL), their relationship with clinicopathological features, and their impact on prognosis.Methods:The tumor tissue sections and formaldehyde fixed paraffin embedded tissues from 174 DLBCL patients diagnosed at the First Affiliated Hospital of Xinjiang Medical University from February 2012 to August 2017 were retrospectively collected. The tissue chips were prepared, and the immunohistochemistry (IHC) method was used to detect the expressions of PD-1 and LAG-3 proteins in tumor infiltrating lymphocytes (TIL) of tissue chips [including whether they were positive (positive for IHC score 1-9 points, negative for 0 point) and expression level (high expression was 4-9 points on IHC score, low expression was 0-3 points)]. The relationship between the expression levels of PD-1 and LAG-3 and the clinicopathological characteristics of patients was analyzed. Spearman correlation coefficient was used to analyze the correlation between the expression levels of PD-1 and LAG-3. Kaplan-Meier method was used to draw overall survival (OS) and progression free survival (PFS) curves of patients with different expression levels of PD-1 and LAG-3, and log-rank test was used for comparison between the groups. Univariate and multivariate Cox proportional hazards models were used to analyze the influencing factors of OS and PFS in patients.Results:Of the 174 DLBCL patients, 95 (54.6%) were male and 79 (45.4%) were female; the median age was 60 years old (5-87 years old). The proportions of patients with PD-1 and LAG-3 positive in TIL of tumor tissues were 79.3% (138/174) and 78.8% (137/174), and the proportions of patients with high expression were 35.6% (62/174) and 37.9% (66/174), respectively. Among patients with bone marrow involvement, the proportion of patients with high expression of PD-1 [62.5% (15/24) vs. 32.5% (39/120), P= 0.006], the proportion of patients with high expression of LAG-3 [54.2% (13/24) vs. 32.5% (39/120), P= 0.050] were higher than those without bone marrow involvement. The expression levels of PD-1 and LAG-3 were not associated with gender, age, clinical stage, international prognostic index score, functional status (PS) score, lactate dehydrogenase level, whether there were B symptoms, whether it was intranodal, tumor length, whether it was germinal center B cell type, number of extranodal involvement sites, and whether it was treated with R-CHOP regimen (all P > 0.05). There was a positive correlation between PD-1 and LAG-3 expression levels in TIL of tumor tissues ( r = 0.202, P = 0.008). Multivariate Cox regression analysis showed that PS score (>2 points vs. ≤2 points: HR = 5.458, 95% CI 2.082-14.307, P = 0.001), R-CHOP regimen treatment (no vs. yes: HR = 2.181, 95% CI 1.086-4.379, P = 0.028) were independent influencing factors of OS, and PS score (>2 points vs. ≤2 points: HR = 3.913, 95% CI 1.579-9.698, P = 0.003), R-CHOP regimen treatment (no vs. yes: HR = 2.609, 95% CI 1.412-4.819, P = 0.024), LAG-3 expression level (low expression vs. high expression: HR = 0.531, 95% CI 0.283-0.995, P = 0.048) were independent influencing factors of PFS. There were no statistical differences in PFS and OS between patients with high and low PD-1 expression levels in TIL (both P > 0.05). PFS and OS in patients with high LAG-3 expression were worse than those in patients with low expression (both P < 0.05). OS in patients with high expressions of PD-1 and LAG-3 was worse than that in patients with low expressions of PD-1 and LAG-3 ( P = 0.044). Conclusions:The expression levels of PD-1 and LAG-3 in TIL of DLBCL patients' tumor tissues are related to bone marrow involvement, which are not related to most other clinicopathological features, and the prognosis of patients with high expressions of PD-1 and LAG-3 is poor.
ABSTRACT
Objective:To investigate the effect and safety of rituximab, programmed death 1 (PD-1) monoclonal antibody, and Bruton tyrosine kinase (BTK) inhibitor on elderly refractory primary central nervous system lymphoma (PCNSL).Methods:The clinical data of an elderly patient with refractory PCNSL treated with the combination of rituximab, PD-1 monoclonal antibody and BTK inhibitor in the First Hospital of Jilin University in February 2020 were retrospectively analyzed. The relevant literature was reviewed.Results:The patient had primary central nervous system diffuse large B-cell lymphoma (high-risk group), and the Memorial Sloan Kettering Cancer Center (MSKCC) score was 2 (estimated overall survival time was 7 months). Disease progressed after 1 course of treatment. Complete remission was achieved after the therapy of rituximab, PD-1 monoclonal antibody combined with BTK inhibitor. PD-1 monoclonal antibody maintenance therapy was performed and patient was followed up until November 17, 2021. The patient's condition was stable. The second progression-free survival (PFS) time was 20 months, and the overall survival time was 21 months. The patient well tolerated the new drug treatment, and no adverse reactions of grade 3 or above occurred.Conclusions:The new targeted combination therapy can be used as a treatment option for elderly PCNSL patients, which can further improve the curative effect and significantly improve the prognosis.
ABSTRACT
Objective To detect the serum level of vitamin D in infants with atopic dermatitis (AD),and to investigate the relationship between the serum level of vitamin D and severity of AD in infants.Methods Clinical data were collected from patients with moderate to severe AD (AD group)through a questionnaire survey in Children's Hospital of Shanxi from February to April in 2016,and the severity of AD was evaluated by the SCORing atopic dermatitis (SCORAD) score.A total of 95 health checkup examinees served as the control group.Enzyme-linked immunosorbent assay (ELISA)was performed to detect the serum level of 25 (OH) D3 in the AD group and control group,as well as the total serum IgE level in the AD group.Blood cell analyzer was used to determine the proportion of blood eosinophils in the AD group.Results A total of 97 patients with AD were enrolled into the study,including 43 (44.3 ％) patients with moderate AD and 54 (55.7％) patients with severe AD.The serum level of 25 (OH) D3 was significantly lower in the AD group than in the healthy control group ([66.71 ± 21.07] nmol/L vs.[85.43 ± 14.87] nmol/L,P ＜ 0.01),as well as in the patients with severe AD than in the patients with moderate AD ([47.54 ± 29.36] nmol/L vs.[63.89 ± 26.67] nmol/L,P =0.006).The proportion of blood eosinophils was significantly higher in the severe AD group than in the moderate AD group (0.124 ± 0.094 vs.0.061 ± 0.060,P ＜ 0.001).There was no significant difference in the total serum IgE level between the moderate AD group and severe AD group (P =0.375).Among the patients with AD,the serum level of 25 (OH) D3 was negatively correlated with the proportion of blood eosinophils (r =-0.336,P ＜ 0.05),but there was no correlation between the serum level of 25 (OH)D3 and total serum IgE level (r =-0.174,P ＞ 0.05).The serum level of 25 (OH)D3 was significantly associated with breastfeeding and vitamin D supplementation (P ＜ 0.05),but unrelated to age,gender,course of disease and acute exudative phase (all P ＞ 0.05).Conclusion The serum level of 25 (OH) D3 is evidently decreased in infants with AD,and vitamin D deficiency is closely related to the severity of AD in infancy.