Dados do Resumo

Título

Analyzing Treatment Outcomes in Head and Neck Cancer Cells: A 3D Model Combining Immune Checkpoint Inhibitors and Radiotherapy

Introdução

Immune checkpoint inhibitors (ICIs) offer a promising treatment for advanced head and neck squamous cell carcinoma (HNSCC), especially when conventional methods fail. Radiotherapy also facilitates the stimulation of the immune system against tumors. Despite their potential, not all patients respond to ICIs. Therefore, it is important to investigate the interactions between tumor cells and lymphocytes to better understand how immune activation and resistance occur.

Objetivo

This study aims to evaluate the interaction between HNSCC cell lines and CD8+ T lymphocytes, using a 3D co-culture model treated with ICIs and radiotherapy, bringing the studied elements closer to their occurrence in the clinic, as they are mimicked by these approaches.

Métodos

The study was evaluated and approved by the institution's ethics and research committee (CEP), under the number 2270/2021. Co-culture models will be established using HNSCC cell lines and CD8+ T lymphocytes isolated from the peripheral blood of healthy individuals. These models will undergo treatment with anti-PD1, anti-TIM-3, and anti-LAG-3, followed by combinations with irradiation. Cell viability, metabolic profile, immunophenotypic profile and immunological mediators will be evaluated by flow cytometry.

Resultados

An initial screening of 6 HNSCC cell lines was carried out to assess their ability to form compact, well-defined spheroids and to evaluate their HPV infection status. The UMSCC1 and UMSCC47 tumor cell lines (HPV- and HPV+, respectively) were selected for co-culture based on the results of multiple tests. Immunofluorescence analysis revealed positive PD-L1 expression in the UMSCC1 cell line, with a similar evaluation planned for UMSCC47. The co-culture model was established using both tumor cell lines and CD8+ T lymphocytes in a 10:1 ratio, after several tests in different cell concentrations. The next steps are to subject the models to treatment with ICIs and radiotherapy, enabling evaluation of cellular behavior and analysis of the obtained results.

Conclusões

We believe it will be possible to identify different response patterns by subjecting these in vitro models to different treatments, which could potentially benefit patients who are responsive to combinations of ICIs and radiotherapy in the future.

Financiador do resumo

FAPESP - 2019/07111-9 and CAPES - 88887.929192/2023-00

Palavras Chave

3D co-culture models; immune checkpoint inhibitors; radiotherapy