Immune checkpoint expression on immune cells of HNSCC patients and modulation by chemoand immunotherapy
Puntigam, Lisa K.
Jeske, Sandra S.
Laban, Simon Andreas
International Journal of Molecular Sciences ; 21 (2020). - Art.-Nr. 5181. - ISSN 1661-6596. - eISSN 1422-0067
Link to original publicationhttps://dx.doi.org/10.3390/ijms21155181
InstitutionsUKU. Klinik für Hals-, Nasen-, Ohrenheilkunde, Kopf- und Halschirurgie
UKU. Klinik für Innere Medizin III
UKU. Institut für Pathologie
External cooperationsDiakonie-Klinikum Stuttgart
Document versionpublished version (publisher's PDF)
Endogenous control mechanisms, including immune checkpoints and immunosuppressive cells, are exploited in the process of tumorigenesis to weaken the anti-tumor immune response. Cancer treatment by chemotherapy or immune checkpoint inhibition can lead to changes of checkpoint expression, which influences therapy success. Peripheral blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) were isolated from head and neck squamous cell carcinoma (HNSCC) patients (n = 23) and compared to healthy donors (n = 23). Immune checkpoint expression (programmed cell death ligand 1 (PD-1), tumor necrosis factor receptor (TNFR)-related (GITR), CD137, tumor necrosis factor receptor superfamily member 4 (TNFRSF4) (OX40), t-cell immunoglobulin and mucin-domain containing-3 (TIM3), B- and T-lymphocyte attenuator (BTLA), lymphocyte-activation gene 3 (LAG3)) was determined on immune cells by flow cytometry. PD-L1 expression was detected on tumor tissue by immunohistochemistry. Immune cells were treated with immunoand chemotherapeutics to investigate treatment-specific change in immune checkpoint expression, in vitro. Specific changes of immune checkpoint expression were identified on PBL and TIL of HNSCC patients compared to healthy donors. Various chemotherapeutics acted differently on the expression of immune checkpoints. Changes of checkpoint expression were significantly less pronounced on regulatory T cells compared to other lymphocyte populations. Nivolumab treatment significantly reduced the receptor PD-1 on all analyzed T cell populations, in vitro. The specific immune checkpoint expression patterns in HNSCC patients and the investigated effects of immunomodulatory agents may improve the development and effcacy of targeted immunotherapy.
Gefördert vom Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg
Is supplemented byhttp://www.mdpi.com/1422-0067/21/15/ 5181/s1
Subject headings[GND]: Plattenepithelcarcinom | Immuntherapie | Immunmodulation
[MeSH]: Squamous cell carcinoma of head and neck | Immunotherapy | Immunomodulation
[Free subject headings]: HNSCC | Head and neck cancer | Immune checkpoints | Checkpoint inhibitors
[DDC subject group]: DDC 610 / Medicine & health
LicenseCC BY 4.0 International
MetadataShow full item record
DOI & citation
Please use this identifier to cite or link to this item: http://dx.doi.org/10.18725/OPARU-34096