Biomarkers associated with immune-related adverse events induced by immune checkpoint inhibitors

Table 4 Immunogenetic biomarkers of immune-related adverse events

Biomarker	ICI type	No. of patients	Study cohort	irAEs type	Judgment	Ref.
HLA-DR15, HLA-B52, HLA-Cw12	CTLA-4, PD-1	11	9 HLA-DR15, 7 HLA-B52, 7 HLA-CW12	Pituitary irAEs	In 11 patients, gene frequencies of HLA-DR15, HLA-B52, and HLA-CW12 were significantly higher in the irAEs-developing group	[73]
HLA- Cw12, HLA- DR15, HLA- DQ7 and HLA- DPw9	CTLA-4, PD-1	62	17/62 (27%) ICI-induced isolated adrenocorticotropic hormone deficiency, 5/62 (8%) ICI-induced hypophysitis	Pituitary irAEs	The positive rates of HLA-CW12, HLA-DR15, HLA-DQ7, and HLA-DPW9 were significantly higher in patients with ICI-induced isolated adrenocorticotropic hormone deficiency, and the positive rates of HLA-CW12 and HLA-DR15 were significantly higher in patients with ICI-induced hypophysitis	[66]
HLA-DR4	PD-1, PD-L1	2960	27/2960 (0.9%) insulin dependent diabetes mellitus	Insulin-dependent diabetes mellitus	The expression of HLA-DR4 gene is related to the incidence of insulin dependent diabetes mellitus	[74]
HLA-B*27:05	PD-L1	290	7/290 (2%) ICI-associated encephalitis	Encephalitis	The occurrence of irAEs encephalitis was significantly correlated with HLA-B *27:05 expression	[75]
HLA-DRB1*11:01, HLA-DQB1*03:01	PD-1, PD-L1, CTLA-4	102	59/102 (58%) irAEs	Itching, colitis	The expression of HLA-DRB1*11:01 was related to the occurrence of pruritus. The expression of HLA-DQB1*03:01 was associated with colitis	[77]
Pre-existing autoimmune disease	CTLA-4, PD-1, PD-L1	4438	It was divided into strict criteria group for autoimmune diseases, lenient criteria group and control group		The prevalence of irAEs was higher in the strict criteria group and the loose criteria group than in the group without pre-existing autoimmune disease	[78]
Single nucleotide polymorphism (30 markers)	CTLA-4, PD-1, PD-L1	89	44/89 (49%) irAEs		A total of 30 variants or single nucleotide polymorphism were identified. Twelve of these were associated with an increased risk of irAEs and 18 with a reduced risk	[87]
MIR146A SNP rs2910164	PD-1, PD-L1	167	The study was conducted in mice and validated with data from cancer patients treated with ICI		MIR146A single nucleotide polymorphism rs2910164 can be used as a biomarker to predict severe irAEs in ICI patients	[90]

irAEs: Immune-related adverse events; ICI: Immune checkpoint inhibitors; HLA: Human leukocyte antigen.