Cancer Immunology, Immunotherapy : CII

Cancer immunotherapy has seen significant success in the last decade for cancer management by enhancing endogenous cancer immunity. However, immunotherapies developed thus far have seen limited success in the majority of high-grade serous carcinoma (HGSC) ovarian cancer patients. This is largely due to the highly immunosuppressive tumour microenvironment of HGSC and late-stage identification. Thus, novel treatment interventions are needed to overcome this immunosuppression and complement existing immunotherapies...

BACKGROUND: Pre-clinical data have revealed that viral infection, such as Hepatitis B virus (HBV), Hepatitis C virus (HCV), and Human Papilloma virus (HPV), may lead to the development of "hot" or "immune-sensitive" tumors, which may impact the efficacy of immune checkpoint inhibitor (ICIs). Therefore, This study aimed to investigate the impact of viral status on the efficacy of ICIs. METHODS: Electronic databases were searched to identify relevant trials. The primary endpoints were overall survival (OS) and progression-free survival (PFS) measured by hazard ratio (HR)...

OBJECTIVE: To construct a prognostic model based on MR features and clinical data to evaluate the progression free survival (PFS), overall survival (OS) and objective response rate (ORR) of pancreatic cancer patients with hepatic metastases who received chemoimmunotherapy. METHODS: 105 pancreatic cancer patients with hepatic metastases who received chemoimmunotherapy were assigned to the training set (n = 52), validation set (n = 22), and testing set (n = 31)...

The Wnt family of secreted proteins are involved in mammary gland development and tumorigenesis. It has recently been shown that Wnt ligands promote M2 macrophage polarization and so we sought to determine the effects of a Wnt signaling antagonist, Secreted Frizzled Related Protein 1 (SFRP1), on M2 marker expression. We measured a murine M2 marker (Arg1) in mice with a targeted deletion of Sfrp1 during different stages of mammary gland development including puberty, pregnancy, and lactation, as well as in response to obesity...

The use of large animal spontaneous models of solid cancers, such as dogs with osteosarcoma (OS), can help develop new cancer immunotherapy approaches, including chimeric antigen receptor (CAR) T cells. The goal of the present study was to generate canine CAR T cells targeting the B7-H3 (CD276) co-stimulatory molecule overexpressed by several solid cancers, including OS in both humans and dogs, and to assess their ability to recognize B7-H3 expressed by canine OS cell lines or by canine tumors in xenograft models...

BACKGROUND: Accumulation studies found that tumor-associated macrophages (TAMs) are a predominant cell in tumor microenvironment (TME), which function essentially during tumor progression. By releasing bioactive molecules, including circRNA, small extracellular vesicles (sEV) modulate immune cell functions in the TME, thereby affecting non-small cell lung cancer (NSCLC) progression. Nevertheless, biology functions and molecular mechanisms of M2 macrophage-derived sEV circRNAs in NSCLC are unclear...

BACKGROUND: Ezabenlimab (BI 754091) is a humanised monoclonal antibody targeting programmed cell death protein-1. We report results from open-label, dose-escalation/expansion, Phase I trials that evaluated the safety, maximum tolerated dose (MTD), pharmacokinetics and antitumour activity of ezabenlimab at the recommended Phase II dose in patients with selected advanced solid tumours. STUDY DESIGN: Study 1381.1 (NCT02952248) was conducted in Canada, the United Kingdom and the United States...

This study aims to investigate the diagnostic potential of IL-2 for PDAC and develop a method to improve the dendritic cell (DC) based vaccine against PDAC. The gene expression data and clinical characteristics information for 178 patients with PDAC were obtained from The Cancer Genome Atlas (TCGA). DCs were isolated from Human peripheral blood mononuclear cells (PBMCs) and were cultured in 4 different conditions. DCs were pulsed by tumor cell lysates or KRAS G12D1 - 23 peptide, and then used to activate T cells...

BACKGROUND: Lipid droplets (LDs) as major lipid storage organelles are recently reported to be innate immune hubs. Perilipin-3 (PLIN3) is indispensable for the formation and accumulation of LDs. Since cancer patients show dysregulated lipid metabolism, we aimed to elaborate the role of LDs-related PLIN3 in oral squamous cell carcinoma (OSCC). METHODS: PLIN3 expression patterns (n = 87), its immune-related landscape (n = 74) and association with B7-H2 (n = 51) were assessed by immunohistochemistry and flow cytometry...

Macrophage polarization is closely associated with the inflammatory processes involved in the development and chemoresistance of colorectal cancer (CRC). M2 macrophages, the predominant subtype of tumor-associated macrophages (TAMs) in a wide variety of malignancies, have been demonstrated to promote the resistance of CRC to multiple chemotherapeutic drugs, such as 5-fluorouracil (5-FU). In our study, we investigated the potential of 23-Hydroxybetulinic Acid (23-HBA), a significant active component of Pulsatilla chinensis (P...

Clinically approved head and neck squamous cell carcinoma (HNSCC) immunotherapies manipulate the immune checkpoint blockade (ICB) axis but have had limited success outside of recurrent/metastatic disease. Interleukin-7 (IL7) has been shown to be essential for effector T-cell survival, activation, and proliferation. Here, we show that IL7 in combination with radiotherapy (RT) is effective in activating CD8 + T-cells for reducing tumor growth. Our studies were conducted using both human papillomavirus related and unrelated orthotopic HNSCC murine models...

BACKGROUND: CD47, serving as an intrinsic immune checkpoint, has demonstrated efficacy as an anti-tumor target in hematologic malignancies. Nevertheless, the clinical relevance of CD47 in gastric cancer and its potential as a therapeutic target remains unclear. METHODS: The expression of CD47 in clinical gastric cancer tissues was assessed using immunohistochemistry and Western blot. Patient-derived cells were obtained from gastric cancer tissues and co-cultured with macrophages derived from human peripheral blood mononuclear cells...

BACKGROUND: Pembrolizumab has been indicated in the treatment of solid tumors with high frequency microsatellite instability (MSI-H) or high tumor mutational burden (TMB-H); however, real-world data on the effectiveness of pembrolizumab with or without chemotherapy in this molecular subset remain limited. Our retrospective study evaluated the clinical efficacy and safety of pembrolizumab in treating advanced solid tumors with either MSI-H or TMB-H. METHODS: This retrospective study analyzed data from 116 patients with MSI-H or TMB-H advanced solid cancers who received pembrolizumab with or without chemotherapy regardless of treatment setting...

BACKGROUND: Inhibition of the adenosine 2A receptor (A2A R) diminishes the immunosuppressive effects of adenosine and may complement immune-targeting drugs. This phase 2 study evaluated the A2A R antagonist AZD4635 in combination with durvalumab or oleclumab in patients with metastatic castration-resistant prostate cancer. METHODS: Patients with histologically/cytologically confirmed disease progressing within 6 months on ≥ 2 therapy lines were randomly assigned to either Module 1 (AZD4635 + durvalumab) or Module 2 (AZD4635 + oleclumab)...

BACKGROUND: Due to individual differences in tumors and immune systems, the response rate to immunotherapy is low in lung adenocarcinoma (LUAD) patients. Combinations with other therapeutic strategies improve the efficacy of immunotherapy in LUAD patients. Although radioimmunotherapy has been demonstrated to effectively suppress tumors, the underlying mechanisms still need to be investigated. METHODS: Total RNA from LUAD cells was sequenced before and after radiotherapy to identify differentially expressed radiation-associated genes...

BACKGROUND: Group 2 innate lymphoid cells (ILC2s) represent one of the main tissue-specific innate lymphoid cell populations, which are key drivers of cytokine secretion in their occupational niche. However, the precise involvement of ILC2s in cancer immunity and their potential impact on immunotherapeutic approaches remain poorly understood. METHODS: The proportion of ILC2s originating from various tissue sources were quantified through flow cytometry, along with the determination of CD4+ T cell and CD8+ T cell percentages...

BACKGROUND: Selective biomarkers may improve outcomes in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) treated with immune checkpoint inhibitor therapy. We investigated three independent biomarkers for association with efficacy in the randomized, phase III KESTREL study (NCT02551159) of first-line durvalumab monotherapy or durvalumab plus tremelimumab versus the EXTREME regimen: programmed cell death ligand-1 (PD-L1) immunohistochemistry, blood tumor mutational burden (bTMB) via circulating tumor DNA, and neutrophil-to-lymphocyte ratio (NLR)...

Pancreatic cancer remains a challenging disease with limited treatment options, resulting in high mortality rates. The predominant approach to managing pancreatic cancer patients continues to be systemic cytotoxic chemotherapy. Despite substantial advancements in immunotherapy strategies for various cancers, their clinical utility in pancreatic cancer has proven less effective and durable. Whether administered as monotherapy, employing immune checkpoint inhibitors, tumor vaccines, chimeric antigen receptors T cells, or in combination with conventional chemoradiotherapy, the clinical outcomes remain underwhelming...

OBJECTIVES: In this study, we aimed to examine parameters of cryoablation, tumor characteristics, and their correlations with distant tumor response and survival of liver metastatic melanoma patients receiving cryoablation and PD-1 blockade (cryo-PD-1) combination treatment. MATERIALS AND METHODS: A retrospective study was conducted among 45 melanoma patients who received combined PD-1 blockade therapy and cryoablation for liver metastasis from 2018 to 2022. Cox regression was utilized to determine the associations between factors and overall survival (OS)...

BACKGROUND: Investigations elucidating the complex immunological mechanisms involved in colorectal cancer (CRC) and accurately predicting patient outcomes via bulk RNA-Seq analysis have been notably limited. This study aimed to identify the immune status of CRC patients, construct a prognostic model, and identify prognostic signatures via bulk RNA sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq). METHODS: The scRNA-seq data of CRC were downloaded from Gene Expression Omnibus (GEO)...