Targeting leucine-rich repeat serine/threonine-protein kinase 2 sensitizes pancreatic ductal adenocarcinoma to anti-PD-L1 immunotherapy.

Pancreatic ductal adenocarcinoma (PDAC) is not sensitive to immune checkpoint blockade therapy, and negative feedback of tumor immune evasion might be partly responsible. We isolated CD8+ T cells and cultured them in vitro. Proteomics analysis was performed to compare changes in Panc02 cell lines cultured with conditioned medium, and leucine-rich repeat kinase 2 (LRRK2) was identified as a differential gene.

Improvement strategy for immune checkpoint blockade: A focus on the combination with immunogenic cell death inducers.

Cancer immunotherapies have yielded promising outcomes in various malignant tumors by blocking specific immune checkpoint molecules, such as programmed cell death 1 and cytotoxic T lymphocyte antigen 4. However, only a few patients respond to immune checkpoint blockade therapy because of the poor immunogenicity of tumor cells and immune-suppressive tumor microenvironment. Accumulating evidence suggests that chemotherapeutic agents, including oxaliplatin and doxorubicin, not only mediate direct cytotoxicity in tumor cells but also induce immunogenic cancer cell death to stimulate a powerful anti-cancer immune response in the tumor microenvironment.

Dynamic profiling of immune microenvironment during pancreatic cancer development suggests early intervention and combination strategy of immunotherapy.

Background: Pancreatic ductal adenocarcinoma (PDAC) has little response to immune checkpoint inhibitors. An in-depth understanding of the immune microenvironment from a comprehensive and dynamic perspective is critical to generate effective therapeutic strategies for PDAC.

Methods: Using mass cytometry and immunohistochemistry, we explored the dynamic changes of tumor-infiltrating immune cells during the development of PDAC in a genetically engineered mouse model (Kras; Trp53; Pdx1-cre) and human specimens.

Oncolytic peptide LTX-315 induces anti-pancreatic cancer immunity by targeting the ATP11B-PD-L1 axis.

Background: LTX-315 is an oncolytic peptide deriving from bovine lactoferrin, with the ability to induce cancer immunogenic cell death. However, the mechanism used by LTX-315 to trigger the antitumor immune response is still poorly understood. The expression of programmed cell death ligand 1 (PD-L1) largely determines the efficacy and effectiveness of cancer immunotherapies targeting this specific immune checkpoint.

A Seven-Gene Signature to Predict Prognosis of Patients With Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant diseases worldwide and has a poor prognosis. Gene-based prognostic models have been reported to predict the overall survival of patients with HCC. Unfortunately, most of the genes used in earlier prognostic models lack prospective validation and, thus, cannot be used in clinical practice.

Preoperative transarterial chemoembolization for barcelona clinic liver cancer stage A/B hepatocellular carcinoma beyond the milan criteria: a propensity score matching analysis.

Background: Debate continues about the benefits of preoperative transarterial chemoembolization (TACE) for treatment of hepatocellular carcinoma (HCC). This study aimed to assess the impact of preoperative TACE on long-term outcomes after curative resection for HCC beyond the Milan criteria.

Methods: Patients who underwent HCC resection exceeding the Milan criteria without macrovascular invasion between 2015 and 2018 were identified (n = 393).

Advantages of targeting the tumor immune microenvironment over blocking immune checkpoint in cancer immunotherapy.

Despite great success in cancer immunotherapy, immune checkpoint-targeting drugs are not the most popular weapon in the armory of cancer therapy. Accumulating evidence suggests that the tumor immune microenvironment plays a critical role in anti-cancer immunity, which may result in immune checkpoint blockade therapy being ineffective, in addition to other novel immunotherapies in cancer patients. In the present review, we discuss the deficiencies of current cancer immunotherapies.

Genomic investigation of co-targeting tumor immune microenvironment and immune checkpoints in pan-cancer immunotherapy.

Drugs that target immune checkpoints (ICPs) have become the most popular weapons in cancer immunotherapy; however, they are only beneficial for a small fraction of patients. Accumulating evidence suggests that the tumor immune microenvironment (TIME) plays a critical role in anti-cancer immunity. This study aimed to assess the potential merits and feasibility of combinational targeting ICPs and TIME in cancer immunotherapy.