PD-L1 on tumor cells is sufficient for immune evasion in immunogenic tumors and inhibits CD8 T cell cytotoxicity

Abstract

Both tumor- and host-derived PD-L1 can play critical roles in immunosuppression; differences in tumor immunogenicity appear to underlie their relative contributions. Juneja et al. show that in immunogenic MC38 tumors, PD-L1 on tumor cells dominates in suppressing tumor immunity by inhibiting CD8 T cell cytotoxicity.

Host expression of PD-L1 determines efficacy of PD-L1 pathway blockade–mediated tumor regression

“…This phenomenon is associated with enhanced T cell activation in PD-L1 -/-and PD-1 -/-mice as compared with WT mice. In addition, differential tumor cell numbers and tumor immunogenicity may potentially be involved in determining different levels of tumor outcomes in the MC38-bearing mouse model (30,31). Thus far, clinical studies with the PD-L1 and PD-1 blockade have not rigorously examined or specifically quantified PD-L1 expression on APC subsets versus tumor cells in TDLNs and tumor tissues in cancer patients (2).…”

Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in colorectal cancer: Relationship with sidedness and prognosis

“…The results from the present study, with immune cell-specific PD-L1 expression being an independent prognostic factor while its expression in tumour cells was not, are coherent with previous research 16 , 23-26 and demonstrate that PD-L1 expression in immune cells and tumour cells might carry different prognostic values and might be regulated by distinct mechanisms. Furthermore, although tumour cell-specific PD-L1 expression has been validated as a predictive marker for response to PD-1 or PD-L1 blockade in several cancers, 11 , 38 , 39 recent studies now suggest that PD-L1 expression in tumour-infiltrating myeloid and T cells also play a critical role in immunosuppression, 38 , 40-43 and should possibly be taken into account in assessment scoring for PD-1/PD-L1 blockade.…”

PD-L1 on host cells is essential for PD-L1 blockade–mediated tumor regression

“…However, the essential or sufficient role of PD-L1 on tumor versus nontumor cells for immune evasion is still unclear (1,22,23). Recently, the importance of PD-L1 on tumor versus host cells during tumor growth has been intensively debated (24)(25)(26)(27). In one study, the role of PD-L1 during tumor formation was studied (25).…”

“…It is suggested that both hostand tumor-PD-L1 contribute to immune suppression during the establishment of tumors (25). In contrast, another study shows that PD-L1 in tumor cells is sufficient for immune evasion (26). In the latter study, a lower cell number was used to slow tumor growth and induce a more robust adaptive immune response.…”

“…In the latter study, a lower cell number was used to slow tumor growth and induce a more robust adaptive immune response. In such a situation, PD-L1 on tumor cells may play a dominant role to prevent tumor clearance in an early phase (26). In addition, it is worth noting that different studies utilized different mouse strains and reagents.…”