Therapeutic effect and mechanism of regulating cellular immune function of chemotherapy combined with PD-1 inhibitor in the first-line treatment of Lewis xenografts / 国际肿瘤学杂志

Objective To investigate the efficacy of chemotherapy combined with programmed death-1 (PD-1) inhibitor in the first-line treatment of Lewis xenografts and its possible mechanism of regulating cellular immune function.Methods Lewis xenografts mouse model was established.The mice were randomly divided into control,chemotherapy,immunotherapy and combination group according to the method of random number table (10 in each group),and each group separately received saline,cisplatinum,PD-1 inhibitor and cisplatinum combined with PD-1 inhibitor.The tumor growth and survival of each group were observed.Flow cytometry was used to detect and compare the proportion of CD8 + T cells and CD4 + CD25 + FOXP3 + regulatory T cells (Treg cells).Results On the second day after treatment,the tumor volume of Lewis xenografts in control group,chemotherapy group,immunotherapy group and combination group were (1 662.0 ± 209.0) mm3,(1 189.2 ±155.6) mm3,(991.1 ± 146.6) mm3 and (761.7-± 141.8) mm3,with statistically significant difference (F =29.78,P ＜ 0.001).The tumor volume in the three treatment groups were significantly smaller than that in control group,combination group was significantly smaller than chemotherapy group and immunotherapy group,and immunotherapy group was significantly smaller than chemotherapy group (all P ＜ 0.05).Three mice died during the experiment (two in control group and one in chemotherapy group).The median survival time of mice in the four groups were 10,12,14 and 18 days,with statistically significant difference (x2 =26.06,P ＜ 0.001).The median survival time of mice in the three treatment groups were significantly longer than that in control group,combination group was significantly longer than chemotherapy group and immunotherapy group,and immunotherapy group was significantly longer than chemotherapy group (all P ＜ 0.05).The proportions of CD8 + T cells in the peripheral blood of the four groups were (28.5 ± 1.2) ％,(33.9 ± 2.9) ％,(34.0 ± 2.5) ％ and (42.4 ± 1.5) ％,with statistically significant difference (F =21.32,P ＜ 0.001).The proportions of CD8 + T cells in the peripheral blood of the three treatment groups were significantly higher than that of control group,and combination group was significantly higher than chemotherapy group and immunotherapy group (all P ＜ 0.05).The proportions of CD8 + T cells in the tumor microenvironment of the four groups were (23.5 ±1.3)％,(26.7 ±1.4)％,(34.2 ±2.8)％ and (41.3 ±2.0)％,with statistically significant difference (F =61.65,P ＜ 0.001).The proportions of CD8 + T cells in the tumor microenvironment of the three treatment groups were significantly higher than that of control group,combination group was significantly higher than chemotherapy group and immunotherapy group,and immunotherapy group was significantly higher than chemotherapy group (all P ＜ 0.05).The proportions of CD4 + CD25 + FOXP3 + Treg cells in the spleen of the four groups were (8.6 ± 0.5) ％,(7.2 ± 0.3) ％,(6.3 ± 0.4) ％ and (5.4 ± 0.4) ％,with statistically significant difference (F =37.06,P ＜ 0.001).The proportions of CD4 + CD25 + FOXP3 + Treg cells in the spleen of the three treatment groups were significantly lower than that of control group,combination group was significantly lower than chemotherapy group and immunotherapy group,and immunotherapy group was significantly lower than chemotherapy group (all P ＜ 0.05).Conclusion Chemotherapy and PD-1 inhibitor can enhance the anti-tumor effect of the body immune system by down-regulating the proportion of Treg cells and upregulating the proportion of CD8 + T cells,etc.Chemotherapy combined with immunotherapy can improve the anti-tumor immune function,inhibit tumor growth and prolong the survival of mouse with xenograft,which were significantly better than chemotherapy and immunotherapy alone.

Value of serum carcinoembryonic antigen in prediction of chemotherapy efficacy and prognosis in patients with advanced non-small cell lung cancer treated with EGFR-tyrosine kinase inhibitor / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to detect the pre- and post-treatment serum carcinoembryonic antigen (CEA) levels after 4 weeks of EGFR-TKIs treatment in advanced non-small cell lung cancer (NSCLC) patients to evaluate the clinical value of CEA in the prediction of chemotherapy response and prognosis in those patients.</p><p><b>METHODS</b>Pre- and post-treatment serum CEA levels of the patients were measured with immunoradiometric kits after 4 weeks of EGFR-TKIs treatment to evaluate the relationship between chemotherapy response and prognosis.</p><p><b>RESULTS</b>After 4 weeks of EGFR-TKIs treatment, one patient in the total of 75 patients (1.3%) achieved complete response (CR), 17 patients (22.7%) achieved partial response (PR), 31 patients (41.3%) achieved disease stable (SD) and 26 patients had progressive disease (PD). The radiological objective response rate(ORR) and disease control rate (DCR) were 24.0% and 65.3%, respectively. The median survival time (MST) of all patients was 8.1 months. The MST of SD patients was similar to that in the OR patients (P = 0.06), but both longer than that in the PD patients (P < 0.001). The MST of DC patients was similar to that in OR patients (P = 0.358), but longer than that in PD patients (P < 0.001). Serum CEA levels decreased ≥ 32% and ≥ 61% were closely related with the objective response and disease control. The median survival time (MST) of patients with serum CEA decreased ≥ 32% was longer than those with CEA decreased < 32% (9.5 months vs 6.7 months, P < 0.0001). The MST of patients with serum CEA decreased ≥ 32% was similar to those with CEA decreased ≥ 61% (9.5 months vs 10.5 months, P = 0.370), but both longer than those with CEA decreased < 32% (6.7 months, P < 0.001). Cox multivariate survival analysis confirmed that serum CEA level decreased ≥ 32%, CEA level decreased ≥ 61%, PS score, and DC are independent prognostic factor, but not OR.</p><p><b>CONCLUSIONS</b>To advanced NSCLC patients, the disease control rate (DCR) may be more suitable than objective response rate (ORR) as an indicator in predicting the efficacy and prognosis in advanced NSCLC patients. Serum CEA levels decreased ≥ 32% may be a reliable indicator to determine the therapeutic efficacy of EGFR-TKIs.</p>

The expression and prognostic significance of ERCC1 and GST-pi in lung cancer / 中国肺癌杂志

<p><b>BACKGROUND AND OBJECTIVE</b>It has been known that the expression levels of ERCC1 and GST-pi were correlated with tumorigenesis and prognosis. The aim of this study is to investigate the relationship between expression levels of ERCC1 and GST-pi, and clinicopathologic parameters and survival in patients with lung cancer.</p><p><b>METHODS</b>The expression levels of ERCC1 and GST-pi were detected by immunohistochemical staining on tissue micro-array sections made of 148 cases of lung cancer and 7 cases of normal lung samples. The results were compared with relevant clinical and pathologic data.</p><p><b>RESULTS</b>Positive rates of ERCC1 and GST-pi were 36.2% and 73.6%, respectively. None of normal lung samples was positive staining. Positive expression of ERCC1 was significantly higher in group of non-small cell lung cancer (NSCLC), highly differentiated and the smokers less than 400 (P < 0.05), positive expression of GST-pi was significantly higher in group of non-smokers and NSCLC (P < 0.05). There were significant correlations between expression of ERCC1 and GST-pi (r = 0.253, P = 0.001). The 5 years survival rate was higher in positive expression of ERCC1. There was significant correlations between expression of ERCC1 and survival (P = 0.037). There was no significant correlations between expression of GST-pi and survival (P = 0.614). Multivariate analysis using Cox regression model showed that expression levels of ERCC1 and GST-pi were not the important independent prognostic factors for survival.</p><p><b>CONCLUSION</b>ERCC1 and GST-pi are aberrant highly expressed in NSCLC with positive correlation, which indicate they might act synergistically in tumorigenesis of NSCLC. The positive expression of ERCC1 have better survival and may have effect on prognosis.</p>

Liver Function of Lymphoma Patients with Chronic HBV Infection after Chemotherapy / 中国肿瘤临床

Objective. To observe the effect of chemotherapy on hepatic function of lymphoma patients with chronic HBV infection. Methods; We used ELISA to detect the serum markers, of HBV and liver function in 207 lymphoma patients and 207 patients with other types of cancer (except pdmary hepatocellular cacinoma). Results: The incidence of HBV infection was higher in lymphoma cancer cases than that in the controlled cases (19.8% vs 9.7%, P=0.004). The incidence of abnormal liver function was higher in lymphoma patients with positive HBsAg than in lymphoma patients without HBsAg (58.5% vs 27.7%, P=0.000). The incidence of ab-normal liver function in lymphoma patients with postive HBsAg was higher than that in patients with other types of cancer with positive HBsAg (58.5 vs 30.0%, P=0.036). The abnormal liver function in lymphoma patients after chemotherapy was associated with HBV infection (P=0.000) but not correlated with age, sex, histological subtype, immune subtype, stage, ECOG PS, and hormone administration. Conclusion: Lymphoma patients with HBV are more likely to have liver function damage after emotherapy.