1949P - Immune suppressive tumour microenvironment and inferior survival of PIK3CG or PIK3CD high expression group in TCGA-Pan cancer cohort

Background

Preclinical studies found that a PI3K-δ blockade could impair T_reg function and a selective PI3K-γ inhibitor could modulate the tumor microenvironment by shifting immunosuppressive M2-like to more inflammatory M1-like tumor-associated macrophage (TAM). Based on this, we aimed to investigate the tumor microenvironment and survival according to PIK3CG and PIK3CD expression in human samples from TCGA-pan cancer database.

Methods

We analyzed 11,069 TCGA pan-cancer samples. The PIK3CG and PIK3CD high expression group were defined as the upper median of each mRNA expression value, whereas the low expression groups were defined as the lower median value. To assess the immune cell composition between expression groups, we adopted the deconvolution algorithm: ‘xCell’. We calculated the mean tumor purity-adjusted T_reg/CD8+ T cell ratio and M2/M1 TAM ratio. We compared overall survival between PIK3CG low vs. high and PIK3CD low vs. high expression groups, respectively.

Results

Median fractions of deconvoluted immune cells including CD8+ T cell, M1 TAM, M2 TAM, and T_reg were increased in the PIK3CG high expression group. This trend was also observed in PIK3CD high expression group except T_reg cell fractions. Tumor purity-adjusted T_reg/CD8+ T cell ratio and M2/M1 TAM ratio increased in the PIK3CG high and PIK3CD high expression groups compared with low expression groups. A total of 10,844 patients with available survival data were collected to compare survival between expression groups. PIK3CG high expression group showed the inferior overall survival compared with low expression group (5-year, 61.2% vs. 58.6%, P=0.002). Worse overall survival was also observed in PIK3CD high expression group rather than low expression group (5-year, 62.7% vs. 57.3%, P<0.001).

Conclusions

PIK3CD or PIK3CG high expression group showed immune-suppressive tumor microenvironment and inferior overall survival in TCGA-Pan cancer cohort. Selective inhibitors of PI3K-γ, PI3K-δ or both could be a viable approach to overcome therapeutic resistance of immune checkpoint blockade in this group of patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.