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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



Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons Creative Commons