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doi:10.22028/D291-38882
Titel: | Interdependence of sequential cytotoxic T lymphocyte and natural killer cell cytotoxicity against melanoma cells |
VerfasserIn: | Friedmann, Kim S. Kaschek, Lea Knörck, Arne Cappello, Sabrina Lünsmann, Niklas Küchler, Nadja Hoxha, Cora Schäfer, Gertrud Iden, Sandra Bogeski, Ivan Kummerow, Carsten Schwarz, Eva C. Hoth, Markus |
Sprache: | Englisch |
Titel: | The Journal of Physiology |
Bandnummer: | 600 |
Heft: | 23 |
Seiten: | 5027-5054 |
Verlag/Plattform: | Wiley |
Erscheinungsjahr: | 2022 |
Freie Schlagwörter: | cancer cells cytotoxic efficiency cytotoxic T lymphocytes human leucocyte antigen immune evasion interleukin-6 MART-1 melanoma natural killer cells resistance |
DDC-Sachgruppe: | 610 Medizin, Gesundheit |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
Abstract: | Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells recognize and eliminate cancer cells. However, immune evasion, downregulation of immune function by the tumour microenvironment and resistance of cancer cells are major problems. Although CTL and NK cells are both important to eliminate cancer, most studies address them individually. We quantified sequential primary human CTL and NK cell cytotoxicity against the melanoma cell line SK-Mel-5. At high effector-to-target ratios, NK cells or melan-A (MART-1)-specific CTL eliminated all SK-Mel-5 cells within 24 h, indicating that SK-Mel-5 cells are not resistant initially. However, at lower effector-to-target ratios, which resemble numbers of the immune contexture in human cancer, a substantial number of SK-Mel-5 cells survived. Pre-exposure to CTL induced resistance in surviving SK-Mel-5 cells to subsequent CTL or NK cell cytotoxicity, and pre-exposure to NK cells induced resistance in surviving SK-Mel-5 cells to NK cells. Higher human leucocyte antigen class I expression or interleukin-6 levels were correlated with resistance to NK cells, whereas reduction in MART-1 antigen expression was correlated with reduced CTL cytotoxicity. The CTL cytotoxicity was rescued beyond control levels by exogenous MART-1 antigen. In contrast to the other three combinations, CTL cytotoxicity against SK-Mel-5 cells was enhanced following NK cell pre-exposure. Our assay allows quantification of sequential CTL and NK cell cytotoxicity and might guide strategies for efficient CTL–NK cell anti-melanoma therapies. |
DOI der Erstveröffentlichung: | 10.1113/JP283667 |
URL der Erstveröffentlichung: | https://physoc.onlinelibrary.wiley.com/doi/10.1113/JP283667 |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-388827 hdl:20.500.11880/35081 http://dx.doi.org/10.22028/D291-38882 |
ISSN: | 1469-7793 0022-3751 |
Datum des Eintrags: | 1-Feb-2023 |
Bezeichnung des in Beziehung stehenden Objekts: | Supporting Information |
In Beziehung stehendes Objekt: | https://physoc.onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1113%2FJP283667&file=tjp15315-sup-0002-s02.xlsx https://physoc.onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1113%2FJP283667&file=tjp15315-sup-0001-s01.pdf |
Fakultät: | M - Medizinische Fakultät |
Fachrichtung: | M - Anatomie und Zellbiologie M - Biophysik |
Professur: | M - Prof. Dr. Markus Hoth M - Keiner Professur zugeordnet |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Dateien zu diesem Datensatz:
Datei | Beschreibung | Größe | Format | |
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The Journal of Physiology - 2022 - Friedmann - Interdependence of sequential cytotoxic T lymphocyte and natural killer cell.pdf | 2,61 MB | Adobe PDF | Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons