Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

    Publikation: Bidrag til tidsskriftReviewpeer review

  1. Lynch syndrome-associated epithelial ovarian cancer and its immunological profile

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Midkine-A potential therapeutic target in melanoma

    Publikation: Bidrag til tidsskriftKommentar/debatForskningpeer review

Vis graf over relationer

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.

OriginalsprogEngelsk
TidsskriftCancer immunology, immunotherapy
ISSN0340-7004
DOI
StatusUdgivet - 9 nov. 2020

ID: 61243165