An important factor associated with primary resistance to immune-checkpoint therapies (ICT) is a "cold" tumor microenvironment (TME), characterized by the absence of T cell infiltration and a non-inflammatory milieu. Whole-exome and RNA sequencing to predict neoantigen expression was performed on the LLC1 cell line which forms "cold" tumors in mice. Dendritic cell (DC)-based vaccination strategies were developed using candidate neoantigen long peptides (LPs). A total of 2536 missense mutations were identified in LLC1 and of 132 candidate neoantigen short peptides, 25 were found to induce CD8 T cell responses. However, they failed to inhibit LLC1 growth when incorporated into a cancer vaccine. In contrast, DCs pulsed with LPs induced CD4 and CD8 T cell responses and one of them, designated L82, delayed LLC1 growth in vivo. By RNA-Seq, CD38 was highly expressed by LLC1 tumor cells and, therefore, anti-CD38 antibody treatment was combined with L82-pulsed DC vaccination. This combination effectively suppressed tumor growth via a mechanism relying on decreased regulatory T cells in the tumor. This study demonstrated that an appropriate vaccination strategy combining neoantigen peptide-pulsed DC with anti-CD38 antibody can render an ICT-resistant "cold" tumor susceptible to immune rejection via a mechanism involving neutralization of regulatory T cells.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583214PMC
http://dx.doi.org/10.3390/cancers13215508DOI Listing

Publication Analysis

Top Keywords

dendritic cell
8
"cold" tumor
8
candidate neoantigen
8
cd8 cell
8
cell responses
8
llc1 growth
8
anti-cd38 antibody
8
regulatory cells
8
cell
7
llc1
6

Similar Publications

Maternal gut microbiota composition contributes to the status of the neonatal immune system and could influence the early life higher susceptibility to viral respiratory infections. Using a novel protocol of murine maternal probiotic supplementation, we report that perinatal exposure to () or () increases the influenza A/PR8 virus (IAV) clearance in neonates. Following either supplementation, type 1 conventional dendritic cells (cDC1) were amplified in the lymph nodes leading to an enhanced IAV antigen-experienced IFN-γ producing effector CD8 T cells in neonates and IAV-specific resident memory CD8 T cells in adulthood.

View Article and Find Full Text PDF

Tuberculosis (TB) remains a significant global health challenge, latently affecting around a quarter of the global population. The sole licensed TB vaccine, Mycobacterium bovis Bacillus Calmette-Guérin (BCG), shows variable efficacy, particularly among adolescents and adults, underscoring the pressing need for more effective vaccination strategies. The administration route is crucial for vaccine efficacy, and administration via the skin, being rich in immune cells, may offer advantages over conventional subcutaneous routes, which lack direct access to abundant antigen-presenting cells.

View Article and Find Full Text PDF

Identification of hub genes, diagnostic model, and immune infiltration in preeclampsia by integrated bioinformatics analysis and machine learning.

BMC Pregnancy Childbirth

December 2024

Department of Gynecology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, 350001, China.

Purpose: This study aimed to identify novel biomarkers for preeclampsia (PE) diagnosis by integrating Weighted Gene Co-expression Network Analysis (WGCNA) with machine learning techniques.

Patients And Methods: We obtained the PE dataset GSE25906 from the gene expression omnibus (GEO) database. Analysis of differentially expressed genes (DEGs) and module genes with Limma and Weighted Gene Co-expression Network analysis (WGCNA).

View Article and Find Full Text PDF

Dynamic therapies such as photodynamic therapy (PDT) and sonodynamic therapy (SDT) have potential in cancer treatment. Microalgae have attracted increasing attention because of their high active mobility, flexibility in terms of functionality, and good biocompatibility. In this study, surface-engineered microalgae Chlorella vulgaris (Chl) modified with metal‒organic framework (MOF) nanoparticles (denoted Chl-MOF) are successfully developed for synergistic photo-sonodynamic therapy and immunotherapy.

View Article and Find Full Text PDF

Neoadjuvant chemotherapy by liposomal doxorubicin boosts immune protection of tumor membrane antigens-based nanovaccine.

Cell Rep Med

December 2024

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center of Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, P.R. China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, P.R. China. Electronic address:

Autologous tumor cell membrane antigen-based vaccines (TMVs) have garnered extensive attention as personalized immunotherapy. However, patients who take TMVs therapy usually undergo various treatments prior to surgery, and these processes modulate the immunogenicity of the tumor membrane and the tumor immune microenvironment. Herein, we investigate the impact of preoperative chemotherapy on the efficacy of TMVs.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!