Table 4.

Key papers describing PD-L1 expression in gastrointestinal HGNEC.

Study	Number of patients	PD-L1 antibody test	PD-L1 Cutoff for positivity	PD-L1 Expression Tumor Cells (TC)	PD-L1 Expression in Stromal Lymphocytes “Immune Cells” (IC)	Other findings
Roberts et al. (66)	GI LCNEC (N=25)	Clone E1L3N; Cell Signaling, Danvers, MA; dilution: 1:200	For TCs, positive expression >1%	3/25 (10%)	5/25 (20%)	In assessment of combined 12 SCNEC and 25 LCNEC PD-L1 was positive on 14% of TCs and 27% of ICs.
			For ICs positive expression ≥1
Xing et al. (67)	GI HGNEC (SCLC/LCNEC not reported) (N=33)	Clone 22C3, dilution 1:50; M365329-8CN, Dako	>1%	9/31 (29%) of HGNEC of the GI tract	N/A	TMB was also measured, range 0.57 to 11.75 mutations/Mb, with a median of 5.68 mutations/Mb
Yang et al. (68)	Gastric HGNEC (N=43) LCNEC = 4	PD-L1 (1:500, ab205921, Abcam)	PD-L1 expression score. Positive cell score x staining intensity. Final score ≥ 4 were classified as PD-L1 high.	21/43 (48.8%) cases (combined LCNEC and SCNEC)	N/A	PD-L1 positive patients had significantly shorter overall survival.
	SCNEC = 39

PD-L1, Programmed death-ligand 1; SCNEC, Small cell neuroendocrine carcinoma; LCNEC, Large cell neuroendocrine carcinoma; HGNEC, High grade neuroendocrine carcinoma; TMB, Tumor mutational burden; Mb, Megabase; N/A, not available.