Table 2.

The role of tumoral YAP/TAZ in regulating tumor immunity

Tumor typeEffector immune cell/checkpointMechanismReferences
Gastric cancerTregsTumoral YAP expression promoted the infiltration of Tregs, which affected tumor progression.97
PDACCTLsYAP expression in tumor cells prevents the activation of CTLs by inhibiting the activation markers Prf1 and Gzmb expression, as well as the proliferation marker Pcna.98
SCC melanoma breast cancerCD8+ T cellYAP/TAZ overexpression unexpectedly suppressed tumor growth in vivo by facilitating CD8+T-cell expansion through TLRs–MYD88/TRIF signaling pathway–mediated activating type I IFN signaling, which provided a novel proof of concept for targeting LATS1/2 in tumor immunotherapy.99
Prostate cancerMDSCsYAP activation induced MDSCs infiltration by promoting Cxcl5 secretion, leading to the impairment of T cell proliferation and tumor-promoting action, which revealed an effective therapeutic way for advanced tumor.102
PDACMDSCsYAP promoted the differentiation and accumulation of MDSCs by inducing IL6 and CSF1–3 expression and secretion, which correlated with the poor survival of patients.98
CRCMDSCsYAP derived MDSCs differentiation and expansion by inhibiting PTEN signaling, contributing to the promotion of tumor growth. High level MDSCs and YAP expression were identified as the predictor for the prognosis of patients with CRC.103, 104
HGOSCMDSCsPRKCI-induced YAP activation and upregulated TNFα expression, recruiting MDSCs and then impairing the infiltration and functions of NK cells and cytotoxic T cells, which afforded an immune therapeutic strategy for highly deadly ovarian cancer.106
MelanomaPD-L1YAP mediated tumor cells evasion of CD8+ T-cell immune responses in a PD-L1–dependent way and targeting of YAP-mediated immune evasion could improve prognosis of patients.113
Breast cancerPD-L1TAZ determining PD-L1 expression in tumor cells occurred in human cells but not in mice, which suppressed T-cells viability and triggered tumor immune evasion.114
MPMPD-L1YAP regulated the PD-L1 in a way similar with above, which promoted tumor progression and was helpful for treatment.115, 116
NSCLCPD-L1YAP regulated PD-L1 at transcriptional levels and PD-1/PD-L1 pathway enhanced endogenous antitumor immune responses.119
Lung cancerPD-L1TAZ participated in lactate-mediated PD-L1 induction through GPR81–cAMP/PKA signaling, suppressing T-cell functions and facilitating tumor immune evasion.120
HCCMacrophagesYAP induced TICAMs recruitment, which functioned as a tumor suppressor by eliminating YAP+ TICs, and it could also inhibit the immunosurveillance-dependent and p53-dependent clearance of TICs starting from the single-cell stage.125
HCCMacrophagesYAP activation in tumor cells induced M1 and M2 macrophages polarization by promoting the production of Mcp1, contributing to liver growth and HCC formation, which provided new targets and strategies to treat HCCs.126
CRCMacrophagesYAP functioned on determining tumor-promoting M2 TAM polarization by elevating the expression of pro-M2 polarization–associated cytokines IL4 and IL13, which promoted IL6 secretion, leading to the tumorigenesis and progression promotion. Increased YAP expression correlated with the poor prognosis in patients with colon cancer. YAP inhibitor Ovatodiolide in combination with the antitumor drug 5-FU obviously suppressed tumorigenesis and TAM infiltration, which implied the potentially promising antitumor therapy.127
Breast cancerMacrophagesTNFα from the CM of macrophages induced YAP expression in tumor cells and promoted the migration of tumor cells via IKKβ/ε signaling mediated the upregulation of HK2.128
  • Abbreviation: CRC, colorectal cancer.