PD-L2 amplification and durable disease stabilization in patient with urothelial carcinoma receiving pembrolizumab

Figures & data

Figure 1. Immunological characterization of unexpectedly durable disease stabilization in urothelial carcinoma patient treated with pembrolizumab. A. Clinical timeline. B. Baseline and follow-up CT scan of hepatic metastasis. C. Design of FISH probes for CD274 and PDCD1LG2 copy number evaluation. D. Representative images for CD274 and PDCD1LG2 amplification by FISH, CD3 and CD8 detection by IHC, PD-L1 expression levels as monitored by the SP142 and 22C3 assays, and hematoxylin and eosin (H&E) stain. FISH, scale bar = 20 µm. IHC, scale bar = 100 µm.

Table 1. Immunological profiling of an urothelial carcinoma case by RNA-seq.

Official	Official		Main	Expression
Symbol	Name	Aliases	Function	Rank
ADORA2A	adenosine A2a receptor	A2aR, ADORA2, RDC8	Adenosine receptor	96
BTLA	B and T lymphocyte associated	BTLA1, CD272	Co-inhibitory receptor	94
CCL2	C-C motif chemokine ligand 2	GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1, SCYA2, SMC-CF	Myeloid infiltration-related cytokine	87
CCR2	C-C motif chemokine receptor 2	CC-CKR-2, CCR-2A, CCR2B, CD192, CKR2, CKR2A, CKR2B, CMKBR2, MCP-1-R, CCR2	Myeloid infiltration-related receptor	99
CD27	CD27 molecule	S152, S152. LPFS2, T14, TNFRSF7, Tp55	Co-stimulatory receptor	95
CD274	CD274 molecule	B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1, PDL1	Co-inhibitory ligand	66
CD28	CD28 molecule	Tp44	Co-stimulatory receptor	94
CD3D	CD3d molecule	CD3-DELTA, IMD19, T3D	CD3 subunit	98
CD3E	CD3e molecule	IMD18, T3E, TCRE	CD3 subunit	93
CD3G	CD3g molecule	CD3-GAMMA, IMD17, T3G	CD3 subunit	99
CD40	CD40 molecule	Bp50, CDW40, TNFRSF5, p50	Co-stimulatory receptor	92
CD40LG	CD40 ligand	CD154, CD40L, HIGM1, IGM, IMD3, T-BAM, TNFSF5, TRAP, gp39, hCD40L	Co-stimulatory ligand	93
CD68	CD68 molecule	GP110, LAMP4, SCARD1	Macrophage biomarker	92
CD8A	CD8a molecule	CD8, Leu2, MAL, p32	CD8 subunit	93
CD8B	CD8b molecule	CD8B1, LEU2, LY3, LYT3, P37	CD8 subunit	95
CXCR6	C-X-C motif chemokine receptor 6	BONZO, CD186, STRL33, TYMSTR	Lymphoid infiltration-related receptor	91
DDX58	DExD/H-box helicase 58	RIG-I, RIGI, RLR-1, SGMRT2	Innate immune sensor	85
GZMA	granzyme A	CTLA3, HFSP	T-cell effector molecule	89
ICOSLG	inducible T cell costimulator ligand	B7-H2, B7H2, B7RP-1, B7RP1, CD275, GL50, ICOS-L, ICOSL, LICOS	Co-stimulatory ligand	88
IFNG	interferon gamma	IFG, IFI	T-cell effector molecule	90
IL10	interleukin 10	CSIF, GVHDS, IL-10A, TGIF, IL10	Anti-inflammatory cytokine	96
LAG3	lymphocyte activating 3	CD223	Co-inhibitory receptor	86
MX1	MX dynamin like GTPase 1	IFI-78K, IFI78, MX, MxA	Biomarker of interferon responses	86
PDCD1	programmed cell death 1	CD279, PD-1, PD1, SLEB2, hPD-1, hPD-l, hSLE1	Co-inhibitory receptor	86
PDCD1LG2	programmed cell death 1 ligand 2	B7DC, Btdc, CD273, PD-L2, PDCD1L2, PDL2, bA574F11.2	Co-inhibitory ligand	86
PRF1	perforin 1	HPLH2, P1, PFP	T-cell effector molecule	84
STAT1	signal transducer and activator of transcription 1	CANDF7, IMD31A, IMD31B, IMD31C, ISGF-3, STAT91	Transcription factor involved in interferon responses	94
TNFRSF14	TNF receptor superfamily member 14	TR2; ATAR; HVEA; HVEM; CD270; LIGHTR	Co-inhibitory receptor	86
VSIR	V-set immunoregulatory receptor	B7H5; GI24; B7-H5; PD-1H; SISP1; VISTA; PP2135; C10orf54; DD1alpha	Co-inhibitory receptor	99

* source https://www.ncbi.nlm.nih.gov/gene/;

** percentile rank of gene expression by RNA-seq as compared to a reference population of 167 patients. RNA quality complied with quality standards as defined in Ref. 22.

Conroy JM, Pabla S, Glenn ST, Burgher B, Nesline M, Papanicolau-Sengos A, Andreas J, Giamo V, Lenzo FL, Hyland FCL, et al. Analytical Validation of a Next-Generation Sequencing Assay to Monitor Immune Responses in Solid Tumors. J. Mol. Diagnostics. 2018;20:95–109. doi:10.1016/j.jmoldx.2017.10.001.

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