ABSTRACT
Objective To comprehensively analyse the immunophenotype of primary pancreatic cancer,providing biological clues for treating pancreatic cancer.Methods The genome nap of 177 primary pancreatic cancer patients from the Cancer Genome Atlas (TCGA) database were enrolled.The overall immune infiltration score (IIS),T cell infiltration score (TIS) and antigen presenting machinery (APM) score were quantified for each specimen.By using unsupervised clustering,the patients were divided into immune-high group and immune-low group according to IIS,TIS,and APM scores.The differences on the inffiltration of immune cell subtype,expression of immune checkpoint and immunological function evaluation were compared between two groups.Results In the radiotherapy population,the survival rate of immune-high group was slightly higher than that of immune-low group with no statistical significance.The immune-high group had more infiltrated neutrophils (63.4％ vs 36.6％),eosinophils (75.5％ vs 24.5％),activated CD4 + memory T lymphocytes (80.7％ vs 19.3％),naive CD4 + T lymphocytes (81.2％ vs 18.8％) and naive B lymphocytes (59.5％ vs 40.5％) compared with immune low group;while the immune-low group had more activated NK cells (67.3％ vs 32.7％),regulatory T lymphocytes (68.9％ vs 31.1％),T follicular helper (67.7％ vs 32.3％),and activated mast cells (62.9％ vs 37.1％).Co-stimulatory molecules such as CD28,ICOS,CD40,CD40L,CD27,CD27L,4-1BB,OX40,GITR and co-inhibitory molecules including CTLA-4,PD-L2,PD-1,VISTA,LAG-3,TIGIT,Galectin-9,TIM-3,and IDO-1 were significantly higher expressed in the immune-low group (all P ＜ 0.05).The PC1 value of principal component analysis of chemokine expression levels and the cytolytic activity (CYT) in the immune-high group were significantly higher (all P ＜0.001).Conclusions Clustering on the three inmune quantification scores could be preliminarily used for immunophenotyping pancreatic cancer.The immune-high group may have synergistic effect with radiation therapy.Treatment with immune checkpoint inhibitor may be effective in immune-low group.
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Objective To identify the effect of stereotactic body radiation therapy (SBRT) on the survival of patients with recurrent pancreatic cancer after surgery.Methods The data of 104 patients with recurrent pancreatic cancer after surgery who underwent SBRT in the Department of Radiation Oncology of Changhai Hospital,Navy Medical University from February 2012 to December 2016 were retrospectively analyzed.The prescription doses ranged from 35-40 Gy/4-8 f.Survival analysis was performed using the Kaplan-Meier method,and relevant factors affecting patients' survival were screened by the Cox proportional hazards model.Results The median overall survival (OS) and progression free survival (PFS) was 12.5 (11.0-14.0) months and 7.3 (6.0-8.7) months,respectively,while the 1-year rate of OS and PFS was 55.8％ and 22.1％,respectively.Multivariate analysis indicated that tumor stage,biological effect dose (α/β =10,BED10),the decrease of CA19-9 level after treatment,and follow-up chemotherapy were all related factors affecting overall survival;tumor stage,BED10,the degree of pain relief and the decrease of CA19-9 level after treatment were related factors affecting PFS.Conclusions Patients suffering recurrent pancreatic cancer with early tumor stage,normal CA19-9 level and mild pain before treatment could be better treated by SBRT,BED10 ≥60 Gy and follow-up chemotherapy after radiotherapy can prolong the survival of patients.
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Objective To investigate the therapeutic methods of hyperpotassemia induced by excessively high blood concentration of tacrolimus (FK506) caused by drug use after renal transplantation. Methods Clinical data of 10 patients diagnosed with hyperpotassemia induced by excessively high blood concentration of FK506 after administration of antifunga l medication following renal transplantation were collected and retrospectively analyzed. Results At 1-2 months after renal transplantation, 10 patients suffered from pulmonary infectiono r pneumonia complicated with pulmonary fungal infection . An appropriate dose of compound sulfamethoxazole, micafungin, cefoperazone sodium-sulbactam sodium and moxifloxacin was administered for antifungal infection. After potassium-lowering therapy, termination of antifungal medication and FK506 dose adjustment (replaced by cyclosporin for certain cases), the serum level of potassium was declined and maintained within normal range for 10 cases. The serum concentration of FK506 was within normal range. No sign of excessively high level of potassium was observed without any potassium-lowering intervention. Conclusions Postoperative administration of drugs is likely to cause excessively high level of FK506 and hyperpotasesmia. Potassium-lowering therapy, termination of drug use and adjustment of immunosuppressive agents should be adopted to avoid the incidence of adverse pharmacologic interaction.