Proteomic profiling and biomarker discovery for predicting the response to PD-1 inhibitor immunotherapy in gastric cancer patients.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment; however, a significant proportion of gastric cancer (GC) patients do not respond to this therapy. Consequently, there is an urgent need to elucidate the mechanisms underlying resistance to ICIs and identify robust biomarkers capable of predicting the response to ICIs at treatment initiation. Methods: In this study, we collected GC tissues from 28 patients prior to the administration of anti-programmed death 1 (PD-1) immunotherapy and conducted protein quantification using high-resolution mass spectrometry (MS). Subsequently, we analyzed differences in protein expression, pathways, and the tumor microenvironment (TME) between responders and non-responders. Furthermore, we explored the potential of these differences as predictive indicators. Finally, using machine learning algorithms, we screened for biomarkers and constructed a predictive model. Results: Our proteomics-based analysis revealed that low activity in the complement and coagulation cascades pathway (CCCP) and a high abundance of activated CD8 T cells are positive signals corresponding to ICIs. By using machine learning, we successfully identified a set of 10 protein biomarkers, and the constructed model demonstrated excellent performance in predicting the response in an independent validation set (N = 14; area under the curve [AUC] = 0.959). Conclusion: In summary, our proteomic analyses unveiled unique potential biomarkers for predicting the response to PD-1 inhibitor immunotherapy in GC patients, which may provide the impetus for precision immunotherapy.

Identification of the exosomal PD-L1 inhibitor to promote the PD-1 targeting therapy of gastric cancer.

Programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) targeting therapy is widely applied in clinics for gastric cancer treatment. Nevertheless, the clinical response is not well acceptable due to the exosomal PD-L1. Hence, abrogation of the exosomal PD-L1 may be a strategy to sensitize the gastric cancer cell to PD-1 targeting therapy. With the aid of CD63 targeting antibody and PD-L1 targeting aptamer, HTRF based assay was established to quantify the exosomal PD-L1, and applied to our in-house compound library, resulting in the identification of moclobemide. Further optimization of moclobemide lead to EP16, which can inhibit the generation of exosomal PD-L1 with IC50 = 0.108 µM. By applying EP16 to gastric cancer cell line coupled with T-cell activity related experiment, it was validated to activate T-cell and can promote the response of PD-1 targeting therapy for gastric cancer treatment in vitro and in vivo. Collectively, our findings give a promising tool to promote the sensitivity of anti-PD-1 for gastric cancer treatment, and EP16 can serve as a leading compound for exosomal PD-L1 abrogation.

New technique of pectoral muscle flap reconstruction for 23 patients with deep sternal wound infections / 中国胸心血管外科临床杂志

@#Objective    To study the effect of deep sternal wound infections（DSWIs）treated by the techniques of pectoral major muscular(PM) turnover and non-suture remain after the wound restitution. Method    We retrospectively analyzed the clinical data of 23 patients with DSWIs in our hospital between June 2016 and December 2016. There were 13 males and 10 females at age of 4-73(54.5±19.5) years. There were 8 patients with concomitant diabetes mellitus and 1 patient with chronic obstructive pulmonary disease(COPD) and brain infarction. Eigteen patients were of type Ⅱ, 5 patients of type Ⅲ according to Pairolero’ classification in the DSWIs. Five patients were with remaining abscess cavity in the mediastinum by thoracic compute tomography(CT). Under general anesthesia the DSWIs debrided thoroughly. The PM elevated from the anterior pectoralis major fascia off subcutaneous tissue to lateral to anterior axillary line, the PM cutted off, then made to the muscle flap, turnover PM flap filled and fixed to sternal wound by lighten tensile suture, the subcutaneous tissue and skin sutured by cutting full-thickness. Results    The sternal reconstruction after debridement of the sternal wound was used by bilateral PM flap in the 17 patients, unilateral PM in 6 patients. There were 21(91.3%) patients in stage Ⅰ healing, 2 patients deferment healing of local cut skin without reoperation. There were 22 patients with non-paradoxical breathing during the postoperation. One death resulted from multiple-organ failure of the concomitant disease. The average of hospital day was 10.6 days. The wound healing was good by chest CT at 1 month after the operation. Conclusion    The sternal forming by the technique of the PM flap turnover, without remain of fremde stoffe in wound for DSWIs is distinctive method, evident effect.