| 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
|
| Resource |
| Human and Animal Cells |
HSC-2(RCB1945)
HSC-3(RCB1975)
HSC-4(RCB1902)
Ca9-22(RCB1976) |
