Cancer cell-intrinsic PD-1: Its role in malignant progression and immunotherapy.

Programmed cell death protein-1 (PD-1), also called CD279, is coded by the PDCD1 gene and is constitutively expressed on the surface of immune cells. As a receptor and immune checkpoint, PD-1 can bind to programmed death ligand-1/programmed death ligand-2 (PD-L1/PD-L2) in tumor cells, leading to tumor immune evasion. Anti-PD-1 and anti-PD-L1 are important components in tumor immune therapy. PD-1 is also expressed as an intrinsic variant (iPD-1) in cancer cells where it plays important roles in malignant progression as proposed by recent studies. However, iPD-1 has received much less attention compared to PD-1 expressed on immune cells although there is an unmet medical need for fully elucidating the mechanisms of actions to achieve the best response in tumor immunotherapy. iPD-1 suppresses tumorigenesis in non-small cell lung cancer (NSCLC) and colon cancer, whereas it promotes tumorigenesis in melanoma, hepatocellular carcinoma (HCC), pancreatic ductal adenocarcinoma (PDAC), thyroid cancer (TC), glioblastoma (GBM), and triple-negative breast cancer (TNBC). In this review, we focus on the role of iPD-1 in tumorigenesis and development and its molecular mechanisms. We also deeply discuss nivolumab-based combined therapy in common tumor therapy. iPD-1 may explain the different therapeutic effects of anti-PD-1 treatment and provide critical information for use in combined anti-tumor approaches.

Therapeutic significance of tumor microenvironment in cholangiocarcinoma: focus on tumor-infiltrating T lymphocytes.

Cholangiocarcinoma (CCA) is a highly aggressive type of adenocarcinoma distinguished by its invasiveness. Depending on specific anatomical positioning within the biliary tree, CCA can be categorized into intrahepatic CCA (ICCA), perihilar CCA (pCCA) and distal CCA (dCCA). In recent years, there has been a significant increase in the global prevalence of CCA. Unfortunately, many CCA patients are diagnosed at an advanced stage, which makes surgical resection impossible. Although systemic chemotherapy is frequently used as the primary treatment for advanced or recurrent CCA, its effectiveness is relatively low. Therefore, immunotherapy has emerged as a promising avenue for advancing cancer treatment research. CCA exhibits a complex immune environment within the stromal tumor microenvironment (TME), comprising a multifaceted immune landscape and a tumor-reactive stroma. A deeper understanding of this complex TME is indispensable for identifying potential therapeutic targets. Thus, targeting tumor immune microenvironment holds promise as an effective therapeutic strategy.

Personal predictive model based on systemic inflammation markers for estimation of postoperative pancreatic fistula following pancreaticoduodenectomy.

BACKGROUND: Postoperative pancreatic fistula (PF) is a serious life-threatening complication after pancreaticoduodenectomy (PD). Our research aimed to develop a machine learning (ML)-aided model for PF risk stratification. AIM: To develop an ML-aided model for PF risk stratification. METHODS: We retrospectively collected 618 patients who underwent PD from two tertiary medical centers between January 2012 and August 2021. We used an ML algorithm to build predictive models, and subject prediction index, that is, decision curve analysis, area under operating characteristic curve (AUC) and clinical impact curve to assess the predictive efficiency of each model. RESULTS: A total of 29 variables were used to build the ML predictive model. Among them, the best predictive model was random forest classifier (RFC), the AUC was [0.897, 95% confidence interval (CI): 0.370-1.424], while the AUC of the artificial neural network, eXtreme gradient boosting, support vector machine, and decision tree were between 0.726 (95%CI: 0.191-1.261) and 0.882 (95%CI: 0.321-1.443). CONCLUSION: Fluctuating serological inflammatory markers and prognostic nutritional index can be used to predict postoperative PF.

Single-center experience of simultaneous bilateral uni-portal video-assisted thoracoscopic surgery for multiple ground-glass opacities.

BACKGROUND: There is an increasing incidence rate of ground-glass opacity (GGO), especially for multiple GGOs (≥2). Whether it is safe and feasible to have bilateral simultaneous surgical resection remains unknown. The purpose of this study is to summarize the experience of surgical resection of patients with multiple GGOs in our Hospital in recent years, and to discuss the above questions. METHODS: Clinical datas of patients who underwent one-stage bilateral uni-portal VATS resections of multiple pulmonary ground glass opacities and had routine pathological examination were collected from May 2016 to May 2019 in our hospital. RESULTS: A total of 34 patients underwent simultaneous bilateral surgical resection of multiple GGO lesions, 28 were women,6 were men, the average age of total patients was 57.9 ± 6.7 years. All patients underwent bilateral uni-portal video-assisted thoracoscopic surgery (Uni-portal VATS), the average intraoperative blood loss was 100.9 ± 67.7 ml, the average operation time was 140 ± 74.8 min, the average thoracic drainage time was 2.8 ± 3.1 days, and the average postoperative hospital stay was 4.2 ± 4.3 days. Postoperative complications including: 2 cases of infection, 3 cases of atrial fibrillation, and 5 cases of persistent air leakage for more than 3 days. All of them improved after treatment, and there were no serious complications and deaths in perioperative period. A total of 76 GGO lesions were resected, with a total malignancy rate of 81.6%, including 40 were pure GGO, of which 28 were malignant (70%), and the average diameter of them were 9.6 ± 3.8 mm; 36 were mixed GGO, of which 34 were malignant (94.4%), the average diameter of them were 15.6 ± 6.6 mm.Mean postoperative follow-up was 28.4 (range, 3-39) months. There was neither recurrence nor deaths at final follow-up. CONCLUSION: The malignancy rate of multiple GGOs is high. Therefore, when the lung function is allowed,one-stage bilateral uni-portal VATS can be considered. According to experience of main surgeon and the frozen biopsy, either sub-lobar resection or lobectomy was acceptable. The risk of postoperative complications and the prognosis were optimal.

Single-stage resection of multiple pulmonary ground-glass opacities: A clinical analysis / 中国胸心血管外科临床杂志

@#Objective    To summarize our experience of surgical resection of multiple ground-glass opacity (GGO) in recent years. Methods    Clinical data of patients who underwent one-stage resections of multiple GGO from November 2015 to May 2019 in our hospital were collected, including 13 males and 52 females at an average age of 56.0±9.4 years. The clinical effects and pathological types of GGO were evaluated. Results    Time interval from first discovery to surgery was 8-1 447 (236.5±362.4) days. There were 48 patients with unilateral surgery and 17 patients with bilateral surgery during the same period. Except for 2 patients who underwent open thoracotomy due to total thoracic adhesions, other patients underwent video-assisted thoracoscopic surgery (VATS). The mean postoperative hospital stay was 12.2±4.3 days. No severe perioperative complication or death occurred. A total of 156 GGO lesions were resected, 80 lesions were pure GGO, including 58 (72.5%) malignant lesions and 22 (27.5%) benign lesions, with an average diameter of 7.7±3.3 mm and 5.5±2.6 mm, respectively. Another 76 lesions were mixed GGO, including 69 (90.8%) malignant lesions and 7 (9.2%) benign lesions, with an average diameter of 13.6±6.6 mm and 7.7±3.5 mm, respectively. Conclusion    Patients with multiple GGO should be treated with anti-inflammatory therapy firstly. When conservative treatment is ineffective and no benign outcomes are observed, surgical treatment should be considered. And when lung function is sufficient for patients to underwent surgeries, the simultaneous unilateral or bilateral thoracoscopic resection is suggested, and the sublobar resection or lobectomy methods can be adopted flexibly according to the clinical features of the lesion and the rapid pathological results, which will not increase the risk of postoperative complications. Otherwise, surgical resection should be given priority for pure GGO lesions with a diameter > 7.7 mm and mixed GGO lesions.