Studies from various cancers with molecular cancer immune signaling pathways

Molecular signaling pathway involved in cancer immune regulation at TMECancerTargetTargeting agentInferenceReference
β-catenin signaling pathwayMetastatic melanoma cancerCancer cellsAnti-PD-L1/anti-CTLA-4 monoclonal antibodiesRelation between active WNT/β-catenin signaling and T-cell gene expression.
Inhibition of CCL4 secretion in cancer cells mediate via transcriptional repressor ATF3 under active WNT/β-catenin signaling.		[53]
STAT3 signaling pathwayHuman non-small cell lung cancer (NSCLC)
Prostate cancer		--Stat3 has inhibitory effect on antitumor NK cell.
Activation pathway represented as Jak2/Stat3 pathway hinders antitumor immunity.		[54]
PI3K/PTEN/AKT/mTOR signaling pathwayBreast cancer
Prostate carcinoma		Cancer cellsB7-H1 siRNAReveals correlation between immunoresistance T-cell mediated through B7-H1 and active PI3k expression in cancer where subsequent treatment with B7-H1 siRNA drops the immunoresistant phenotype in cancer cells. Further overexpression of B7-H1 protein with lower PI3k expression adopts the protumor nature.[55]
Lung adenocarcinomas
Squamous cell carcinomas		Cancer cells and antitumor immune responsemTOR inhibitor + PD-1 antibodyActive involvement of oncogenic AKT-mTOR signaling in regulation of PD-L1 expression.
Post treatment with mTOR inhibitor and PD-1 antibody has targeted tumor and increased the antitumor immune response. Intratumoral injection of an AKT inhibitor also enhanced the therapeutic efficacy of an E7-specific vaccine or E7-specific CD8+ T cell adoptive transfer against immune-resistant tumors.		[56, 57]
p53 signaling pathwayLiver carcinoma
Breast tumor		Cancer, NK cells and infiltrating lymphocytes-Reveals tumor regression, associated with restoration of wild type tumor suppressor p53 expression which enable recruitment of NK cells driven by cytokine release.
Studies reveal mutational status of tumor suppressor gene is correlated with lymphocytic infiltration.		[58]
NF-κB signaling pathwayOvarian cancerDCs and macrophagesDHMEQ (NF-κB inhibitor)Constitutive expression of NF-κB is symbolic to oncogenic drive at TME. Subsequent administration of DHMEQ (NF-κB inhibitor) overcome the suppressed immune response in human immune cells (DCs and macrophages) when cultured in supernatant derived from epithelial ovarian cancer cells.[59]
RAS/RAF/MAPK signaling pathwayHuman lung adenocarcinoma (NSCLC cell lines)Cancer and adaptive immune T cellsAnti-PD-1 antibody (pembrolizumab)/ERK inhibitorKRAS mutation introduced immune suppression.
Targeting at p-ERK signaling reverses it.		[60]
Melanoma cancerAdaptive immune cellsImmune checkpoint blockers + inhibitors of MEK/BRAFStudies reveal role of BRAF mutation in constitutive expression of MAPK pathway and its impact on adaptive immune functioning, blocking the same with respective pathway inhibitors (MEK/BRAF) along with immune checkpoint blockers reverses the protumor immune functioning towards antitumor response inhibiting tumor growth.[38, 61]
Melanoma cancerMDSCsBRAF inhibitorsPresence of BRAF inhibitor reduces MDSC infiltration but resistant to BRAF inhibitor restores the same with activation of MAPK signaling pathway, downstream regulation focuses on increased myeloid attractant for their recruitment at TME.[41, 62]

siRNA: small interfering RNA; -: not applicable