Understanding the role of PD-L1/PD1 pathway blockade and autophagy in cancer therapy

Figures & data

Figure 1 Schematic representation of the interaction of tumor cells with the immune system.

Notes: Upper panel represents the unperturbed mechanism of interaction between PD1 with PD-L1 in homeostasis conditions. Lower panel demonstrates the effects of the blockade of the interaction between a tumor cell and a lymphocyte T-cell when there is a PD1 and or PD-L1 inhibitor present (X). It shows the upregulation of autophagy as a defense mechanism.
Abbreviations: IFNγR, interferon gamma receptor; MHC, major histocompatibility complex; PD1, programmed cell death receptor-1; PD-L1, programmed cell death receptor-1 ligand; TCR, T-cell receptor.

Table 1 Autophagy inhibitors and their targets

Drug name	Target
Early stage inhibitors
3-methyladenine	Class III PI3K
Wortmanin	Class III PI3K
LY294002	Class III PI3K
Late stage inhibitors
Chloroquine, hydroxychloroquine	Lysosomal function
Bafilomycin	Lysosomal function
Monesin	Lysosomal function

Abbreviation: PI3K, phosphoinositol-3 kinase.

Table 2 Combination therapy between a chemotherapy agent and an autophagy inhibitor

Drug combination	Stage of development
HCQ + imatinib	Phase II
HCQ + gemcitabine	Phase I/II
HCQ + erlotinib	Phase II
HCQ + bortezomib	Phase I/II
HCQ + temozolomide	Phase I
CQ + bortezomib	In vitro, in vivo

Abbreviations: CQ, chloroquine; HCQ, hydroxychloroquine.

Table 3 Summary of biologic (monoclonal antibodies) inhibitors of the PD-L1/PD1 axis

Drug name	Status	Target
Nivolumab	FDA approved	PD1
Pembrolizumab	FDA approved	PD1
Atezolizumab	FDA approved	PD-L1
MEDI4736	FDA approved	PD-L1

Abbreviations: FDA, Food and Drug Administration; PD1, programmed cell death-1; PD-L1, programmed cell death-1 ligand.