STK11 expression

The decreased expression of LKB1 in BMMSCs may activate the Wnt signaling pathway, leading to increased PD-L1 expression. This inhibited CD4+ T cell proliferation, which might lead to impaired anti-tumor immunity in AML patients and promote AML progression.

Furthermore, 7 IRGs, namely CALCA, BMP6, S100P, THPO, CGA, PCSK1 and MUC5AC, were found significantly overexpressed in STK11-mutated NSCLC in both LUSC and LUAD histology. Low STK11 expression at protein level and presence of STK11 mutation were associated with poor prognosis in NSCLC, and mutated STK11 might probably alter the expression IRGs profiling.

LKB1 expression may serve as a potential biomarker for poor outcomes after receiving radiation in LA-NSCLC patients. Further studies to confirm the association and application are warranted.

In this series, LKB1 expression was negatively associated with the presence of CD8+ TILs. Future studies will evaluate pts treated with chemoimmunotherapy and expand TIME analysis.

Subsequent rescue assays demonstrated that STK11 mutations hindered ferroptosis by impacting the synthesis of MUFAs in LUAD cells. This study provided evidence that STK11 mutations suppressed ferroptosis in LUAD cells by promoting MUFA synthesis, thus offering a novel research direction in the management of LUAD.

Finally, in DU145 cells lacking the LKB1 gene, exogenously induced LKB1 expression restored AMPK phosphorylation by auraptene, indicating the essential role of LKB1. In summary, auraptene is a potent AMPK activator that acts by elevating the AMP/ATP ratio, thereby potentially suppressing prostate cancer progression, via at least three molecular mechanisms, including suppression of the mTOR-S6K pathway, reduced lipid synthesis, and AR downregulation caused by AMPK activation.

Our analysis demonstrated significantly lower PD-L1 expression in NSCLC patients with BrMet and STK11m compared to STK11wt. STK11m demonstrated a poor correlation with PD-L1 and TMB. This association may impact response to therapy and prognosis in patients with STK11m.

The complement pathway is a central part of the innate immune system and emerging data have identified local tumor induced complement pathway effector generation as distinct from peripheral complement components. Tumor produced complement factors can modulate tumor signaling and the TME promoting tumor growth and immune evasion. Our study implicates the complement pathway as a potential therapeutic target in STK11 mutant NSCLC with the growth of Stk11-KO tumors dependent on tumor-derived C3 suppressing T-cell immunity and these effects potentially mediated through the recruitment of PMN in the TME through the Cxcr2 signaling axis.

Alteration of STK11 mutational or mRNA/protein status might be used as a potential predictive biomarker for the prognosis of the clinical outcomes in CCA patients.

In conclusion, LKB1 expression is related to tumor size, differentiation, depth of invasion, lymph node metastasis, and TNM stage, and low LKB1 expression can predict a poor prognosis. LKB1 is a potentially valuable prognosis signature and therapeutic target in GC patients.

Moreover, we found that the injection of the DCs with limited LKB1 expression before tumor inoculation could reduce their production of granzyme B (P<0.0001) and perforin (P=0.0042) from CD8+T cells, thereby impairing their cytotoxicity and promoting tumor growth. Our data suggest that LKB1 can enhance DC-mediated T cell immunity by restraining Treg development and thereby suppressing tumor growth.

STK11 knockdown or miR-130b-3p overexpression attenuated the function of circDENND2D overexpression on NSCLC cells. CircDENND2D inhibited metastasis and immune escape of NSCLC by regulating miR-130b-3p/STK11 axis.