A chimeric peptide promotes immune surveillance of senescent cells in injury, fibrosis, tumorigenesis and aging.

The accumulation of senescent cells can lead to tissue degeneration, chronic inflammatory disease and age-related tumorigenesis. Interventions such as senolytics are currently limited by off-target toxicity, which could be circumvented by instead enhancing immune-mediated senescent cell clearance; however, immune surveillance of senescent cells is often impeded by immunosuppressive factors in the inflammatory microenvironment. Here, we employ a chimeric peptide as a 'matchmaker' to bind to the urokinase-type plasminogen activator receptor, a cell surface marker of senescent cells.

An Immunomodulator-Boosted Lactococcus Lactis Platform For Enhanced In Situ Tumor Vaccine.

In situ vaccination is an attractive type of cancer immunotherapy, and methods of persistently dispersing immune agonists throughout the entire tumor are crucial for maximizing their therapeutic efficacy. Based on the probiotics usually used for dietary supplements, an immunomodulator-boosted Lactococcus lactis (IBL) strategy is developed to enhance the effectiveness of in situ vaccination with the immunomodulators. The intratumoral delivery of OX40 agonist and resiquimod-modified Lactococcus lactis (OR@Lac) facilitates local retention and persistent dispersion of immunomodulators, and dramatically modulates the key components of anti-tumor immune response.

Acidity-targeting transition-aided universal chimeric antigen receptor T-cell (ATT-CAR-T) therapy for the treatment of solid tumors.

The use of CAR-T cells in treating solid tumors frequently faces significant challenges, mainly due to the heterogeneity of tumor antigens. This study assessed the efficacy of an acidity-targeting transition-aided universal chimeric antigen receptor T (ATT-CAR-T) cell strategy, which is facilitated by an acidity-targeted transition. Specifically, the EGFRvIII peptide was attached to the N-terminus of a pH-low insertion peptide.

Potent antitumor activity of a bispecific T-cell engager antibody targeting the intracellular antigen KRAS G12V.

Kirsten Rat Sarcoma viral oncogene homolog (KRAS) is one of the most frequent oncogenes. However, there are limited treatment options due to its intracellular expression. To address this, we developed a novel bispecific T-cell engager (BiTE) antibody targeting HLA-A2/KRAS G12V complex and CD3 (HLA-G12V/CD3 BiTE).

Efficacy and safety of second-line therapy by S-1 combined with sintilimab and anlotinib in pancreatic cancer patients with liver metastasis: a single-arm, phase II clinical trial.

Background: Pancreatic adenocarcinoma carries a grim prognosis, and there are few recognized effective second-line treatment strategies. We attempted to evaluate the efficacy and safety of a combination of S-1, sintilimab, and anlotinib as a second-line treatment in pancreatic cancer patients with liver metastasis.

Methods: Pancreatic cancer patients with liver metastases were recruited.

Self-assembled nanoparticles: A new platform for revolutionizing therapeutic cancer vaccines.

Cancer vaccines have had some success in the past decade. Based on in-depth analysis of tumor antigen genomics, many therapeutic vaccines have already entered clinical trials for multiple cancers, including melanoma, lung cancer, and head and neck squamous cell carcinoma, which have demonstrated impressive tumor immunogenicity and antitumor activity. Recently, vaccines based on self-assembled nanoparticles are being actively developed as cancer treatment, and their feasibility has been confirmed in both mice and humans.

PD-1 blockade plus chemoradiotherapy as preoperative therapy for patients with BRPC/LAPC: A biomolecular exploratory, phase II trial.

This is a phase II study of PD-1 blockade plus chemoradiotherapy as preoperative therapy for patients with locally advanced or borderline resectable pancreatic cancer (LAPC or BRPC, respectively). Twenty-nine patients are enrolled in the study. The objective response rate (ORR) is 60%, and the R0 resection rate is 90% (9/10).

Biomarkers for predicting tumor response to PD-1 inhibitors in patients with advanced pancreatic cancer.

Pancreatic cancer is among the most lethal malignant neoplasms, and few patients with pancreatic cancer benefit from immunotherapy. We retrospectively analyzed advanced pancreatic cancer patients who received PD-1 inhibitor-based combination therapies during 2019-2021 in our institution. The clinical characteristics and peripheral blood inflammatory markers (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], lymphocyte-to-monocyte ratio [LMR], and lactate dehydrogenase [LDH]) were collected at baseline.

Efficacy and safety of immune checkpoint inhibitors in advanced pancreatic cancer: A real world study in Chinese cohort.

Previous clinical studies had not shown expected results in advanced pancreatic cancer (APC) with single-agent checkpoint inhibitors. Until the present day, little is known about their performance in real-world settings. So, in this study, we investigate the ICIs' efficacy and safety in Chinese APC patients.

Distributed Scheduling Strategy of Virtual Power Plant Using the Particle Swarm Optimization Neural Network under Blockchain Background.

Large-scale and widely dispersed distributed energy resource (DER) can be gathered by a virtual power plant (VPP) in a given area, and its parameters can be combined into a single external operation profile. Each distributed energy source in the VPP has a complete backup of the critical information for the entire network because it is a node of blockchain. The distribution network can be accessed by DER freely and adaptable under the scientific management of the VPP, and it can offer the system high-reliability, high-quality, and high-security power services.

Case Report: Pathologic Complete Response to Induction Therapy in a Patient With Potentially Resectable Pancreatic Cancer.

Immune monotherapy does not appear to work in patients with pancreatic cancer so far. We are conducting a clinical trial that combines programmed cell death protein-1 (PD-1) inhibitor with chemotherapy and concurrent radiotherapy as induction therapy for patients with locally advanced pancreatic cancer (LAPC) and borderline resectable pancreatic cancer (BRPC). Here, we report a case with a pathologic complete response (pCR) and no postoperative complications after the induction therapy.

Molecular Landscape and Prognostic Biomarker Analysis of Advanced Pancreatic Cancer and Predictors of Treatment Efficacy of AG Chemotherapy.

Purpose: Although mutational analysis of pancreatic cancer has provided valuable clinical information, it has not significantly changed treatment prospects. The purpose of this study is to further investigate molecular alterations in locally advanced pancreatic cancer and identify predictors of the efficacy of nab-paclitaxel plus gemcitabine (AG) chemotherapy.

Experimental Design: Tumor samples from 118 pancreatic cancer patients who received AG chemotherapy as first-line treatment were sequenced and genomic profile was generated.

Use of Nab-Paclitaxel Plus Gemcitabine Followed by Hypofractionated Tomotherapy With Simultaneous Integrated Boost in Patients With Locally Advanced Pancreatic Cancer.

Background And Purpose: A phase 2 study LAPACT indicated nab-paclitaxel plus gemcitabine (AG) improved outcomes of patients with locally advanced pancreatic cancer (LAPC). Conventional radiotherapy failed to show benefit, indicating high dose to volume with high risk of recurrence is needed. The high dose can be delivered through hypofractionated tomotherapy with simultaneous integrated boost (SIB).

Advanced Pancreatic Cancer Patient Benefit From Personalized Neoantigen Nanovaccine Based Immunotherapy: A Case Report.

Personal neoantigen vaccines are considered to be effective methods for inducing, amplifying and diversifying antitumor T cell responses. We recently conducted a clinical study that combined neoantigen nanovaccine with anti-PD-1 antibody. Here, we reported a case with a clear beneficial outcome from this treatment.

AGIG Chemo-Immunotherapy in Patients With Advanced Pancreatic Cancer: A Single-Arm, Single-Center, Phase 2 Study.

Background: To date, chemotherapy remains the only effective treatment of unresectable pancreatic adenocarcinoma. In the past few years, the interest in immunological anticancer therapy rises sharply. AGIG is a novel chemo-immunotherapy regimen that combines nab-paclitaxel + gemcitabine chemotherapy with sequential recombinant interleukin-2 (IL-2) and granulocyte-macrophage colony stimulating factor (GM-CSF) therapy.

IL-6 promotes metastasis of non-small-cell lung cancer by up-regulating TIM-4 via NF-κB.

Objectives: Interleukin-6 (IL-6) is critical for the development of non-small-cell lung cancer (NSCLC). Recently, we identified T-cell immunoglobulin domain and mucin domain 4 (TIM-4) as a new pro-growth player in NSCLC progression. However, the role of TIM-4 in IL-6-promoted NSCLC migration, invasion and epithelial-to-mesenchymal transition (EMT) remains unclear.

SPINK1 promotes cell growth and metastasis of lung adenocarcinoma and acts as a novel prognostic biomarker.

Serine protease inhibitor Kazal type 1 (SPINK1) plays a role in protecting the pancreas against premature activation of trypsinogen and is involved in cancer progression. SPINK1 promoted LAC cells growth, migration, and invasion. Mechanistically, we found that SPINK1 promoted LAC cells migration and invasion via up-regulating matrix metalloproteinase 12 (MMP12).

Advanced Lung Cancer Is Associated with Decreased Expression of Perforin, CD95, CD38 by Circulating CD3+CD8+ T Lymphocytes.

It is known that dysregulation of the immune system is closely related to the development of lung cancer and that CD8+T lymphocytes play a critical role in antitumor immunity. We analyzed the percentage of CD3+CD8+ T cells in peripheral blood, and expressions of the activated molecules, perforin, CD95, CD28, HLA-DR and CD38 in circulating CD3+CD8+ T cells from 68 lung cancer cases with stage I∼II and 61 lung cancer cases with stage III∼IV by flow cytometry. 61 lung cancer cases with stage III∼IV were followed up for more than 6 months and survival time was recorded.

Increased Tim-3 expression in peripheral NK cells predicts a poorer prognosis and Tim-3 blockade improves NK cell-mediated cytotoxicity in human lung adenocarcinoma.

T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) has been shown to play an important role in mediating NK-cell function in human diseases. However, the relationship between Tim-3 expression in natural killer (NK) cells and human lung adenocarcinoma remains unclear. We therefore investigated the expression of Tim-3 in NK cells and explored the effect of Tim-3 blockade on NK cell-mediated activity in human lung adenocarcinoma.

Tim-3 expression by peripheral natural killer cells and natural killer T cells increases in patients with lung cancer--reduction after surgical resection.

Background: The purpose of this study was to investigate Tim-3 expression on peripheral CD3-CD56+ natural killer (NK) cells and CD3+CD56+ natural killer T (NKT) cells in lung cancer patients.

Materials And Methods: We analyzed Tim-3+CD3-CD56+ cells, Tim-3+CD3-CD56dim cells, Tim-3+CD3-CD56bright cells, and Tim- 3+CD3+CD56+ cells in fresh peripheral blood from 79 lung cancer cases preoperatively and 53 healthy controls by flow cytometry. Postoperative blood samples were also analyzed from 21 members of the lung cancer patient cohort.

Increased expression of T cell immunoglobulin and mucin domain 4 is positively associated with the disease severity of patients with ankylosing spondylitis.

Monocytes and associated cytokines have been shown to be involved in the pathogenesis of ankylosing spondylitis (AS). T cell immunoglobulin and mucin domain 4 (Tim-4) was identified on monocytes/macrophages and dentritic cells (DCs) and plays important roles in regulating the activities of macrophages and DCs. The current study investigated the association between Tim-4 expression and AS.