Background: Treatment with immunotherapy can elicit varying responses across cancer types, and the mechanistic underpinnings that contribute to response vrsus progression remain poorly understood. However, to date there are few preclinical models that accurately represent these disparate disease scenarios.
Methods: Using combinatorial radio-immunotherapy consisting of PD-1 blockade, IL2Rβγ biased signaling, and OX40 agonism we were able to generate preclinical tumor models with conflicting responses, where head and neck squamous cell carcinoma (HNSCC) models respond and pancreatic ductal adenocarcinoma (PDAC) progresses.
Results: By modeling these disparate states, we find that regulatory T cells (Tregs) are expanded in PDAC tumors undergoing treatment, constraining tumor reactive CD8 T cell activity. Consequently, the depletion of Tregs restores the therapeutic efficacy of our treatment and abrogates the disparity between models. Moreover, we show that through heterotopic implantations the site of tumor development defines the response to therapy, as implantation of HNSCC tumors into the pancreas resulted in comparable levels of tumor progression.
Conclusions: This work highlights the complexity of combining immunotherapies within the tumor microenvironment (TME) and further defines the immune and non-immune components of the TME as an intrinsic feature of immune suppression.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749720 | PMC |
http://dx.doi.org/10.1136/jitc-2024-010405 | DOI Listing |
Front Cell Infect Microbiol
January 2025
Department of Oncology, Faculty of Medicine, Comenius University, Bratislava and National Cancer Institute, Bratislava, Slovakia.
The microbiome-gut-testis axis has emerged as a significant area of interest in understanding testicular cancer, particularly testicular germ cell tumors (TGCTs), which represent the most common malignancy in young men. The interplay between the gut and testicular microbiomes is hypothesized to influence tumorigenesis and reproductive health, underscoring the complex role of microbial ecosystems in disease pathology. The microbiome-gut-testis axis encompasses complex interactions between the gut microbiome, systemic immune modulation, and the local microenvironment of the testis.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Pathology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.
Colorectal cancer (CRC) is one of the most prevalent and deadly malignancies worldwide. Recently, ferroptosis, a novel form of regulated cell death characterized by iron dependency and lipid peroxidation, has garnered significant attention from researchers. The mechanisms underlying ferroptosis, including intracellular iron levels, lipid peroxidation, and antioxidant system regulation, offer new insights into cancer treatment strategies.
View Article and Find Full Text PDFFront Immunol
January 2025
BIOCEV, First Faculty of Medicine, Charles University, Vestec, Czechia.
Despite enormous progress, advanced cancers are still one of the most serious medical problems in current society. Although various agents and therapeutic strategies with anticancer activity are known and used, they often fail to achieve satisfactory long-term patient outcomes and survival. Recently, immunotherapy has shown success in patients by harnessing important interactions between the immune system and cancer.
View Article and Find Full Text PDFFront Immunol
January 2025
Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Today, cancer has become one of the leading global tragedies. It occurs when a small number of cells in the body mutate, causing some of them to evade the body's immune system and proliferate uncontrollably. Even more irritating is the fact that patients with cancers frequently relapse after conventional chemotherapy and radiotherapy, leading to additional suffering.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, China.
Background: Adenocarcinoma of the esophagogastric junction (AEGJ) is a highly aggressive tumor that frequently metastasizes to the liver. Understanding the cellular and molecular mechanisms that drive this process is essential for developing effective therapies.
Methods: We employed single-cell RNA sequencing to analyze the tumor heterogeneity and microenvironmental landscape in patients with AEGJ liver metastases.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!