Exploring Tumor Modeling and Immunotoxicology - Precision-Cut Tumor Slices of Head and Neck Squamous Cell Carcinoma and Immune Response to Nanoplastics

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a heterogenous cancer with poor prognosis, especially for patients with advanced or recurrent disease. The complex tumor microenvironment (TME) plays an important role in mediating immune evasion and therapy resistance. To improve preclinical testing, advanced 3D in vitro and ex vivo models such as spheroids, organoids, and tumor slice cultures have been developed, offering a physiologically relevant environment for investigating tumor–immune interactions and evaluating therapeutic efficacy.

In the first part of this study, current in vitro and ex vivo models of HNSCC were reviewed and an ex vivo model using precision-cut tumor slices (PCTS) from gingival tumors was established. Tumor slices were generated using a vibratome and cultured for 48 hours. Viability in different culture media, cell composition and responsiveness to stimulation were evaluated by flow cytometry. The results showed that both cancer cells and immune cells remained viable during culture. Additionally, the model captured patient-specific differences in cell composition and immune infiltration. This supports the use of ex vivo cultures of PCTS in preclinical research. However, further optimization and validation in larger cohorts as well as for other subtypes of HNSCC tumors, are needed.

In the second part of this study, the increasing concern of micro- and nanoplastics (MNPs) and their effect in health was addressed. These particles can be inhaled or ingested, potentially leading to their accumulation in tonsils, the first immunologically active tissues exposed to such particles. Given the proximity of tonsils to primary sites of HNSCC and that local and systemic immune response can develop here, it is important to understand the impact of MNPs on the immune system. Therefore, the in vitro effect of linear low-density polyethylene (LLDPE) and tire wear (TW) nanoplastics on monocyte-derived dendritic cell (moDC) activation was evaluated by flow cytometric analysis of the activation markers CD86 and HLA-DR. TW particles, but not LLDPE particles strongly activated moDCs. However, the activating effect was not observed after sterile filtration. This suggests that nanoplastics can activate moDCs, but this effect appears to be dependent on plastic type and potentially the presence of contaminants.

Together, these findings provide a foundation for future studies aimed at improving preclinical modelling in HNSCC and understanding the immunological impact of nanoplastics.

Popular Abstract

Head and neck squamous cell carcinoma (HNSCC) is a common type of cancer found in the head and neck area. Despite progress in cancer research, this disease remains hard to treat, especially when it spreads or returns. One reason is that cancer cells can develop ways to escape both the immune system and treatments. To better understand this and advance drug-development, new lab models that better mimic original tumors are being developed. One such model is precision-cut tumor slices (PCTS). PCTS are thin slices of real tumors that can be kept alive in the lab for a short time. A big advantage with this model is that the original tumor structure and cell content is preserved.
In the first part of this study, a model using PCTS from gum tumors was established. The results showed that both tumor and immune cells remained viable in the slices for 48 hours. The model also captured differences in tumor composition between patients. This means that the model could be useful for studying tumor biology and how they respond to new therapies. However, the model needs further improvement and testing on other types of HNSCC tumors.

The second part of this study looked at the effects of micro- and nanoplastics on the immune system. These small particles are formed when larger plastic items break down and are now widespread in the environment. Recently, they have also been found in human blood and tissues, but their effects on human health are not well understood. To learn more, the effects of tire wear (TW) and linear low-density polyethylene (LLDPE) nanoplastics on dendritic cells were studied. Dendritic cells are immune cells that help the body to recognize and respond to foreign particles, such as viruses. The results showed that TW but not LLDPE particles could activate the dendritic cells. When the TW particles were sterile filtrated to remove potential contaminants, they no longer activated the cells. Together, this suggests that nanoplastics can activate our immune system, but this effect is dependent on plastic type and potentially contaminants that are attached to the plastics and that were removed during the filtration. These findings provide early insight into the effects of nanoplastics on the immune system, but more research is needed to fully determine how they impact human health.

• author: Landberg, Julia
• supervisor: Christina Sakellariou
• organization: Department of Immunotechnology
• course: KIMM05 20251
• year: 2025
• type: H2 - Master's Degree (Two Years)
• subject: Medicine and Health Sciences; Biology and Life Sciences; Technology and Engineering
• keywords: Immunotechnology, Tumor modelling, Immunotoxicology, Nanoplastics
• language: English
• id: 9198509
• date added to LUP: 2025-06-13 12:51:52
• date last changed: 2025-06-13 12:51:52