RRC ID 80996
Author Takatsuka D, Tachinami H, Suzuki N, Yamazaki M, Yonesi A, Takaichi M, Imaue S, Yamada SI, Tanuma JI, Noguchi M, Tomihara K.
Title PAK4 inhibition augments anti-tumour effect by immunomodulation in oral squamous cell carcinoma.
Journal Sci Rep
Abstract Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumours, warranting novel treatments. Here, we examined the therapeutic efficacy of inhibiting p21 activated kinase 4 (PAK4) in OSCC and determined its immunomodulatory effect by focusing on the enhancement of anti-tumour effects. We examined PAK4 expression in OSCC cells and human clinical samples and analysed the proliferation and apoptosis of OSCC cells following PAK4 inhibition in vitro. We also investigated the effects of in vivo administration of a PAK4 inhibitor on immune cell distribution and T-cell immune responses in OSCC tumour-bearing mice. PAK4 was detected in all OSCC cells and OSCC tissue samples. PAK4 inhibitor reduced the proliferation of OSCC cells and induced apoptosis. PAK4 inhibitor significantly attenuated tumour growth in mouse and was associated with increased proportions of IFN-γ-producing CD8+ T-cells. Furthermore, PAK4 inhibitor increased the number of dendritic cells (DCs) and up-regulated the surface expression of various lymphocyte co-stimulatory molecules, including MHC-class I molecules, CD80, CD83, CD86, and CD40. These DCs augmented CD8+ T-cell activation upon co-culture. Our results suggest that PAK4 inhibition in OSCC can have direct anti-tumour and immunomodulatory effects, which might benefit the treatment of this malignancy.
Volume 14(1)
Pages 14092
Published 2024-6-18
DOI 10.1038/s41598-024-64126-0
PII 10.1038/s41598-024-64126-0
PMID 38890401
MeSH Animals Apoptosis / drug effects CD8-Positive T-Lymphocytes / drug effects CD8-Positive T-Lymphocytes / immunology Carcinoma, Squamous Cell* / drug therapy Carcinoma, Squamous Cell* / immunology Carcinoma, Squamous Cell* / metabolism Carcinoma, Squamous Cell* / pathology Cell Line, Tumor Cell Proliferation* / drug effects Dendritic Cells / drug effects Dendritic Cells / immunology Dendritic Cells / metabolism Female Humans Immunomodulation* / drug effects Male Mice Mouth Neoplasms* / drug therapy Mouth Neoplasms* / immunology Mouth Neoplasms* / metabolism Mouth Neoplasms* / pathology p21-Activated Kinases* / antagonists & inhibitors p21-Activated Kinases* / metabolism
Human and Animal Cells HSC-2(RCB1945) HSC-3(RCB1975) HSC-4(RCB1902) Ca9-22(RCB1976)