Investigating The T Cell Repertoire In Melanoma Immune Checkpoint Inhibitor Therapy Patients and Their Response To Therapy
In the study presented, changes to CD4+ T Cells, CD8+ T Cells and their reactivity to stimuli by Immune Checkpoint Inhibitor (ICI) Therapy are investigated. Findings are compared to healthy donors and patients’ course of therapy, to better predict response to therapy, development of immune-related adverse effects (irAEs), patient benefit and survival.
The study is part of an ongoing Master Thesis.
Tumors can exhibit immune-evasion mechanisms by expressing checkpoint ligands, e.g. PD-L1 and CTLA-4 ligands. This can be abrogated by ICIs, which bind immune checkpoint molecules and prevent their ligands from interacting, restoring anti-tumor responses.
Since 2011, multiple ICIs have been approved for treatment of melanoma in Germany. However, irAEs may arise in up to 45% of ICI patients, depending on the dose, time and type of agent used.
To characterize the T cell department, samples from healthy donors and melanoma patients were intra- and extracellularly analyzed using Flow Cytometry (FACS) by staining surface markers of CD4+ subsets, CD8+ cells and transcription factors Tbet, GATA3, RORγt and FoxP3. So far, characterizing assays have been developed and verified for healthy donors.
Currently, healthy donor samples are being incubated with anti-CD3/CD28 or melanoma cell culture supernatant to investigate their reactivity to stimuli. Results will subsequently be compared to melanoma ICI therapy patients.