Impact of oncogenic pathways on evasion of antitumour immune responses

Key Points T cell infiltration into the tumour microenvironment (TME) is an important feature for the therapeutic activity of checkpoint blockade therapy. While T cell activation can be influenced in multiple ways, oncogenic signalling within tumour cells has the potential to mediate T cell exclusion from the tumour microenvironment. Some oncogenic pathways, such as activation of WNT–β-catenin and MYC, mediate failed T cell recruitment through failed accumulation or activation of antigen-presenting cells. Within the antigen-presenting cell compartment, dendritic cells driven by the transcription factor basic leucine zipper transcriptional factor ATF-like 3 (BATF3) seem to be of critical importance for priming of tumour-specific CD8 + T cells. Other oncogenic signalling pathways, such as loss of function of liver kinase B1 (LKB1) mutations, mediate recruitment of immune suppressive cell populations, which in turn mediate exclusion of T cells from the TME. This Review describes tumour cell-intrinsic oncogenic pathways implicated in tumour immune evasion and highlights the potential for targeting these pathways to overcome resistance to immunotherapy in various cancer types. Immunotherapeutic interventions are showing effectiveness across a wide range of cancer types, but only a subset of patients shows clinical response to therapy. Responsiveness to checkpoint blockade immunotherapy is favoured by the presence of a local, CD8 + T cell-based immune response within the tumour microenvironment. As molecular analyses of tumours containing or lacking a productive CD8 + T cell infiltrate are being pursued, increasing evidence is indicating that activation of oncogenic pathways in tumour cells can impair induction or execution of a local antitumour immune response. This Review summarizes our current knowledge of the influence of oncogenic effects on evasion of antitumour immunity.