Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

The effects of targeted immune-regulatory strategies on tumor-specific T-cell responses in vitro

Research output: Contribution to journalJournal articleResearchpeer-review

  1. In vitro 4-1BB stimulation promotes expansion of CD8+ tumor-infiltrating lymphocytes from various sarcoma subtypes

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. TAM-ing T cells in the tumor microenvironment: implications for TAM receptor targeting

    Research output: Contribution to journalReviewpeer-review

  1. The capacity of CD4+ Vγ9Vδ2 T cells to kill cancer cells correlates with co-expression of CD56

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Loss of Ambra1 promotes melanoma growth and invasion

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

BACKGROUND: Immune-related adverse events (IrAEs) are auto-immune reactions associated with immune checkpoint inhibitor-based therapy (ICI). Steroids are currently the first-line option for irAE management; however, recent studies have raised concerns regarding their potential impairment of tumor-specific immune responses. In this study, we investigated the in vitro effects of commonly used irAE treatment drugs on the anti-tumor activity of tumor-infiltrating lymphocytes (TILs).

METHODS: Impairment of anti-tumor immune responses by four drugs (antibodies: vedolizumab and tocilizumab; small molecules: mycophenolate mofetil and tacrolimus) reported to be effective in treating irAEs was tested at clinically relevant doses in vitro and compared to a standard moderate dose of corticosteroids (small molecules) or infliximab (antibodies). TIL responses against autologous tumor cell lines, in the presence or absence of irAE drugs, were determined by flow cytometry (short-term tumor-specific T-cell activation) or xCELLigence (T-cell-mediated tumor killing).

RESULTS: None of the tested antibodies influenced T-cell activation or T-cell-mediated tumor killing. Low-dose mycophenolate and tacrolimus did not influence T-cell activation, whereas higher doses of tacrolimus (> 1 ng/ml) impaired T-cell activation comparably to dexamethasone. All tested small molecules impaired T-cell-mediated tumor killing, with high-dose tacrolimus reducing killing at levels comparable to dexamethasone-mediated inhibition. In addition, mycophenolate and tacrolimus alone also demonstrated anti-proliferative effects on tumor cells.

CONCLUSIONS: These data support clinical testing of targeted immune-regulatory strategies in the initial phase of irAE management, as a potential replacement for corticosteroids.

Original languageEnglish
JournalCancer immunology, immunotherapy
ISSN0340-7004
DOIs
Publication statusPublished - 9 Nov 2020

ID: 61243165