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

Objective: In this study,the clinical efficacy and safety of photodynamic therapy and its combination with chemotherapy,targeted therapy,and immunotherapy in patients with advanced gastric cancer will be examined,Related factors that may have an impact on the efficacy will also be examined,and initially explore the possible mechanism of photodynamic therapy in the immune system of these patients.Methods: Between November 2019 and November 2022 at the Lanzhou University Second Hospital,90 patients with advanced gastric cancer who had been diagnosed with pathology and imaging were gathered,and photodynamic therapy was applied to the tumor lesions after injecting the photosensitizer.Different drugs were given to patients according to their conditions after photodynamic therapy.The efficacy and adverse reactions were evaluated in different time periods,and the survival of patients with long-term follow-up data was analyzed.The immune cell in peripheral blood and local tumor tissues were detected before and after PDT.Results:(1)Instant period efficacy of PDT: 48 h after PDT,local lesion necrosis of varying degrees occurred in all patients,with a 94.4% significant necrosis(MON+SN)rate.1 week after PDT,the significant necrosis rate was 100.0%.The obstruction symptoms of 22 patients(56.4%)were completely relieved at 1 week after PDT.CA72-4 show a significantly declined 1 week after PDT.(2)Short-term efficacy of PDT: Endoscopic evaluation 2 months after PDT revealed that 55 cases(61.1%)achieved SR and 10 cases(11.1%)achieved CR,with an overall efficiency(CR+SR+MR)of 100.0% and a significant efficiency(SR+CR)of 72.2%,among which the significant efficiency(83.0%)of Borrmann type III patients was significantly higher than that of Borrmann type II(55.6%)and Borrmann type IV(61.8%).(3)Efficacy of combination therapy: It was discovered that CR 3 cases(8.57%),PR 16 cases(45.71%),SD 11 cases(31.43%),PD 5 cases(14.29%),ORR54.29%,and DCR 85.71%,among which male ORR and DCR were significantly better than female after evaluating the efficacy of 35 patients with PDT combined treatment.The level of CEA and CA72-4 considerably decreased after combination treatment.The median survival time for all patients was 10 months and the cumulative survival rates at 3,6,12,and 24 months were 79.9%,63.5%,36.1%,and14.7%,respectively.(4)Related factors: The short-term efficacy of PDT may be significantly impacted by Borrmann type(P=0.045)and these factors,like preoperative KPS score(P=0.012),clinical stage(P=0.005),Borrmann type(P=0.002),tumor site(P=0.012),tumor size(P=0.017),whether there was combined targeting and immunotherapy(P=0.002),and whether there was combined surgery(P=0.008),can significantly affect the survival and prognosis of patients.(5)Safety evaluation: Recent adverse reactions of PDT mainly included fever(38.9%),abdominal pain(48.9%)and nausea(36.7%),all of which were grade 1-2 and haematological toxic reactions were grade 1.Following a combination of treatments,nausea(60.5%),vomiting(23.7%),fatigue(44.7%),hypertension(14.5%)and hand-foot syndrome(7.9%)are the main adverse reactions,and no symptoms of grade3 or above occurred.28 patients(36.2%)experienced grade 1-3 myelosuppression.(6)Changes of immune cells: Peripheral blood samples from stage III patients had considerably less CD3+,CD3+CD4+,CD3+CD8+,CD4+CD45RA+,CD4+CD45RO+cells and CD4+CD25+CD127-% after PDT 48 h than samples from patients before PDT.Conversely,Stage IV patients had considerably more CD3+,CD3+CD4+,CD3+CD8+,and CD4+CD45RA+ cells in their peripheral blood after PDT 48 h than they had before PDT.HE staining of pathological tissue sections showed that many inflammatory cells gathered to tumor tissues after PDT,and Immunohistochemical revealed that the number of CD3+T cells,CD4+T cells,CD8+T cells and macrophages increased significantly after PDT,while the change of B cells and NK cells was not significant.Conclusion: Photodynamic therapy can regulate peripheral inflammatory cells and local tumor immune cells,to shrink the tumor rapidly and effectively.It can be used as an effective treatment for advanced gastric cancer either alone or in combination with other therapies.