Targeting PCSK9 reduces cancer cell stemness and enhances antitumor immunity in head and neck cancer.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been demonstrated to play a critical role in regulating cholesterol homeostasis and T cell antitumor immunity. However, the expression, function, and therapeutic value of PCSK9 in head and neck squamous cell carcinoma (HNSCC) remain largely unexplored. Here, we found that the expression of PCSK9 was upregulated in HNSCC tissues, and higher PCSK9 expression indicated poorer prognosis in HNSCC patients. We further found that pharmacological inhibition or siRNA downregulating PCSK9 expression suppressed the stemness-like phenotype of cancer cells in an LDLR-dependent manner. Moreover, PCSK9 inhibition enhanced the infiltration of CD8+ T cells and reduced the myeloid-derived suppressor cells (MDSCs) in a 4MOSC1 syngeneic tumor-bearing mouse model, and it also enhanced the antitumor effect of anti-PD-1 immune checkpoint blockade (ICB) therapy. Together, these results indicated that PCSK9, a traditional hypercholesterolemia target, may be a novel biomarker and therapeutic target to enhance ICB therapy in HNSCC.
Pubmed ID: 37305703 RIS Download
Research resources used in this publication
None foundAdditional research tools detected in this publication
Antibodies used in this publication
- Mouse Anti-Human CD44 Monoclonal Antibody, Unconjugated, Clone 156-3C11 (RRID:AB_2076465)
- Rabbit (DA1E) mAb IgG XP Isotype Control (RRID:AB_1550038)
- Rabbit monoclonal D4W2Z anti-CD8 (RRID:AB_2756376)
- FoxP3 (D6O8R) Rabbit mAb (RRID:AB_2797979)
- ALDH1A1 (D9Q8E) XP® Rabbit mAb (RRID:AB_2799452)
- Sox2 (D1C7J) XP® Rabbit mAb (RRID:AB_2798664)
- Brilliant Violet 421(TM) anti-human/mouse Granzyme B Recombinant (RRID:AB_2810603)
- PE anti-mouse IFN-gamma (RRID:AB_315402)
- APC anti-mouse TNF-alpha (RRID:AB_315429)
- PE anti-mouse Ly-6G (RRID:AB_1186099)
- APC anti-mouse Ly-6C (RRID:AB_1732076)
- MHC Class II (I-A/I-E) Monoclonal Antibody (M5/114.15.2), Brilliant Violet™ 421, eBioscience (RRID:AB_2925530)
- FITC anti-mouse/human CD11b (RRID:AB_312789)
- PE anti-mouse CD279 (PD-1) (RRID:AB_1877231)
- APC anti-mouse CD366 (Tim-3) (RRID:AB_2562998)
- PerCP anti-mouse CD8a (RRID:AB_893423)
- CD4 Monoclonal Antibody (GK1.5), eFluor™ 450, eBioscience (RRID:AB_10718983)
- FITC anti-mouse CD3 (RRID:AB_312661)
- CD45 Monoclonal Antibody (30-F11), PE-Cyanine5.5, eBioscience (RRID:AB_469718)
- APC/Cyanine7 anti-mouse CD45 (RRID:AB_312981)
- GAPDH antibody (RRID:AB_2737588)
- Beta Actin antibody (RRID:AB_2883836)
- Ki-67 (D3B5) Rabbit mAb (Mouse Preferred; IHC Formulated) (RRID:AB_2620142)
- Granzyme B (D6E9W) Rabbit mAb (RRID:AB_2799313)
- Arginase-1 (D4E3M™) XP® Rabbit mAb (RRID:AB_2800207)
- Anti-Human CD8a (D8A8Y)-162Dy (RRID:AB_2909535)
- CD133 (D2V8Q) XP(R) (RRID:AB_2721172)
- BMI1 antibody (RRID:AB_2065392)
- SREBF2 antibody (RRID:AB_2881091)
- HMGCR antibody (RRID:AB_2877957)
- LDLR antibody (RRID:AB_2281164)
- PCSK9 Antibody (RRID:AB_2918134)
Associated grants
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This is a list of tools and resources that we have found mentioned in this publication.
C57BL/6J (tool)
RRID:IMSR_JAX:000664
Mus musculus with name C57BL/6J from IMSR.
View all literature mentionsMouse Anti-Human CD44 Monoclonal Antibody, Unconjugated, Clone 156-3C11 (antibody)
RRID:AB_2076465
This monoclonal targets Human CD44
View all literature mentionsRabbit (DA1E) mAb IgG XP Isotype Control (antibody)
RRID:AB_1550038
This isotype control targets not applicable
View all literature mentionsRabbit monoclonal D4W2Z anti-CD8 (antibody)
RRID:AB_2756376
This recombinant monoclonal targets CD8
View all literature mentionsFoxP3 (D6O8R) Rabbit mAb (antibody)
RRID:AB_2797979
This monoclonal targets FOXP3
View all literature mentionsALDH1A1 (D9Q8E) XP® Rabbit mAb (antibody)
RRID:AB_2799452
This monoclonal targets ALDH1A1
View all literature mentionsSox2 (D1C7J) XP® Rabbit mAb (antibody)
RRID:AB_2798664
This monoclonal targets SOX2
View all literature mentionsBrilliant Violet 421(TM) anti-human/mouse Granzyme B Recombinant (antibody)
RRID:AB_2810603
This recombinant monoclonal targets Granzyme B
View all literature mentionsPE anti-mouse IFN-gamma (antibody)
RRID:AB_315402
This monoclonal targets IFN-gamma
View all literature mentionsAPC anti-mouse TNF-alpha (antibody)
RRID:AB_315429
This monoclonal targets TNF-alpha
View all literature mentionsPE anti-mouse Ly-6G (antibody)
RRID:AB_1186099
This monoclonal targets Ly-6G
View all literature mentionsAPC anti-mouse Ly-6C (antibody)
RRID:AB_1732076
This monoclonal targets Ly-6C
View all literature mentionsMHC Class II (I-A/I-E) Monoclonal Antibody (M5/114.15.2), Brilliant Violet™ 421, eBioscience (antibody)
RRID:AB_2925530
This monoclonal targets MHC Class II (I-A/I-E)
View all literature mentionsFITC anti-mouse/human CD11b (antibody)
RRID:AB_312789
This monoclonal targets CD11b
View all literature mentionsPE anti-mouse CD279 (PD-1) (antibody)
RRID:AB_1877231
This monoclonal targets CD279
View all literature mentionsAPC anti-mouse CD366 (Tim-3) (antibody)
RRID:AB_2562998
This monoclonal targets CD366
View all literature mentionsPerCP anti-mouse CD8a (antibody)
RRID:AB_893423
This monoclonal targets CD8a
View all literature mentionsCD4 Monoclonal Antibody (GK1.5), eFluor™ 450, eBioscience (antibody)
RRID:AB_10718983
This monoclonal targets CD4
View all literature mentionsFITC anti-mouse CD3 (antibody)
RRID:AB_312661
This monoclonal targets CD3
View all literature mentionsCD45 Monoclonal Antibody (30-F11), PE-Cyanine5.5, eBioscience (antibody)
RRID:AB_469718
This monoclonal targets CD45
View all literature mentionsAPC/Cyanine7 anti-mouse CD45 (antibody)
RRID:AB_312981
This monoclonal targets CD45
View all literature mentionsGAPDH antibody (antibody)
RRID:AB_2737588
This monoclonal targets GAPDH
View all literature mentionsBeta Actin antibody (antibody)
RRID:AB_2883836
This monoclonal targets Beta Actin
View all literature mentionsKi-67 (D3B5) Rabbit mAb (Mouse Preferred; IHC Formulated) (antibody)
RRID:AB_2620142
This monoclonal targets Ki-67
View all literature mentionsGranzyme B (D6E9W) Rabbit mAb (antibody)
RRID:AB_2799313
This monoclonal targets GZMB
View all literature mentionsArginase-1 (D4E3M™) XP® Rabbit mAb (antibody)
RRID:AB_2800207
This monoclonal targets ARG1
View all literature mentionsAnti-Human CD8a (D8A8Y)-162Dy (antibody)
RRID:AB_2909535
This monoclonal targets CD8a
View all literature mentionsCD133 (D2V8Q) XP(R) (antibody)
RRID:AB_2721172
This monoclonal targets CD133
View all literature mentionsSREBF2 antibody (antibody)
RRID:AB_2881091
This polyclonal targets SREBF2
View all literature mentionsHMGCR antibody (antibody)
RRID:AB_2877957
This polyclonal targets HMGCR
View all literature mentionsPCSK9 Antibody (antibody)
RRID:AB_2918134
This polyclonal targets PCSK9
View all literature mentions
