PDT Improves The Clinical Efficacy Of Advanced Obstructive Esophageal Cancer By Regulating Peripheral Immune Function And Improving Local Immune Microenvironment

Objective:To evaluate the short-term tumor-shrinking effect of photodynamic therapy(PDT)and to explore the long-term inhibition effect and potential mechanism of combined chemotherapy,immunotherapy,and targeted therapy after PDT treatment for advanced esophageal cancer.Methods:Clinical information of 61 patients with advanced obstructive esophageal cancer admitted to the Department of Tumor Surgery of Lanzhou University Second Hospital from November 2019 to November 2022 was retrospectively analyzed,and patients were divided into 4 groups according to the post-PDT treatment:PDT+chemotherapy group(PDT+C),PDT+chemotherapy+immunotherapy group(PDT+C+I),PDT+targeted therapy+immunotherapy group(PDT+T+I),and PDT+chemotherapy+targeted therapy+immunotherapy group(PDT+C+T+I)were evaluated in different time periods.The tumor tissue changes,clinical manifestations and laboratory examination of esophageal cancer patients before and 48h after PDT were recorded and detected.Flow cytometry was employed to measure alterations in peripheral blood immune function before and after PDT treatment,while immunohistochemical staining was utilized to investigate changes in immune cell infiltration in esophageal cancer tissue before and after PDT treatment.The survival time and long-term survival status of the patients were observed and recorded.Results:The short-term effective rate after PDT was 100%(61/61)and the significant effective rate was 90.4%(55/61).The objective response rate(ORR)was73.8%and disease control rate(DCR)was 91.8%.The dysphagia score decreased from 1.59±0.08 points before PDT to 0.52±0.06 points after PDT(p<0.05).After PDT treatment,endoscopy showed different degrees of tumor necrosis,including mild necrosis in 8 cases(13.1%),moderate necrosis in 24 cases(39.3%),and severe necrosis in 29 cases(47.5%).The overall survival rates at 3 months,6 months,1 year and 2 years were 89.3%,79.2%,37.6%and 20%,respectively.The overall median survival time was 12 months(3-30 months).The duration of the combined treatment was 6.9 months in the PDT+C group,8.4 months in the PDT+C+I group,12.6 months in the PDT+C+T+I group and 14.2 months in the PDT+T+I group.The main adverse reactions after PDT alone were chest pain and acid reflux discomfort(75.4%).The incidence of severe adverse reactions such as tumor site bleeding(5.0%),photoallergy(1.6%)and perforation(0)was low.PDT combined treatment of the main adverse reactions of leukopenia(78.7%),thrombocytopenia(75.4%)and AST levels(49.2%).Cox univariate regression analysis showed that lesion circumference(p=0.003),lesion necrosis(p=0.0001),KPS score(p<0.0001),and previous radiotherapy history(p=0.045)were the factors affecting the efficacy of PDT.Cox multivariate regression analysis revealed that tumor lesion circumference(p=0.002),lesion necrosis after PDT(p=0.001),KPS score(p<0.001),combined treatment after PDT(p=0.023)were independent risk factors affecting patient survival.According to the results of peripheral immune blood of patients,48h after PDT,the systemic immune function of stageⅢpatients decreased,while that of stageⅣpatients increased,and the local infiltration of CD3~+T cells,CD4~+T cells,CD8~+T cells,CD20~+B cells,macrophages and other immune cells in tumor tissue increased significantly.Peripheral blood immune checkpoint LAG3 and PD-1 decreased significantly after combined treatment,and the difference was statistically significant.HE staining of tumor tissues before and after PDT manifested that compared with before PDT treatment,a large number of inflammatory cells infiltrated after PDT treatment.Immunohistochemical staining demonstrated that after PDT,the local infiltration of CD3~+T cells,CD4~+T cells,CD8~+T cells,CD20~+cells and CD68~+cells(macrophages)increased,while the number of CD163~+cells(macrophages)and PD-1~+cells decreased significantly.Conclusion:Photodynamic therapy can shrink the tumor rapidly and solve dysphagia symptoms effectively.Patients with KPS score greater than 80,tumor lesion circumference less than 1/2 lumen,severe necrosis of tumor tissue after PDT treatment,and previous radiotherapy were more likely to benefit.Photodynamic therapy can improve peripheral immune function and tumor local immune microenvironment by regulating the expression of peripheral inflammatory cells and tumor local immune cells.PDT combined with multiple drugs can effectively prolong the survival of patients with advanced esophageal cancer.