In addition, as a negative regulator of PI3K/Akt/mTOR signaling pathway, loss of PTEN leads to upregulation of PD-L1 protein, decrease of CD8 + T cell and increase of TAM, which are negative predictors of PD-1 blocking response in microsatellite instability-high (MSI-H) CRC patients [228,229]. Here, PIK3CA is linked to colorectal carcinoma.