Dynamic interplay of oncogenes and T cells induces PD-L1 in the tumor microenvironment

Abstract

Tumor-infiltrating T cells have recently been found to upregulate immunosuppressive pathways, such as programmed cell death protein 1 ligand 1 (PD-L1), in a paracrine fashion on tumor cells, but tumor cell-intrinsic regulation of PD-L1 is another potential mechanism. In this issue of Cancer Discovery, Akbay and colleagues show that signaling via mutant EGF receptor (EGFR) in murine lung tumor cells directly upregulates tumor PD-L1 and that therapeutic blockade of this pathway improves survival in EGFR-driven preclinical models-highlighting the dynamic interplay and therapeutic opportunities of cancer cell biology and immune biology.

Figure 1

Oncogene vs. T cell driven immune checkpoint pathway upregulation. Tumor cells can induce PD-L1 expression in a cell autonomous manner via the oncogene EGFR. Alternatively, PD-1 pathway upregulation can be the consequence of CD8 T cell infiltration. These models generate different hypotheses to identify patients who will benefit from immune checkpoint blocking therapies. Future studies may resolve the contribution of each mechanism in various malignancies.