Bruton tyrosine kinase inhibitors in B-cell lymphoma: beyond the antitumour effect

Table 2 Immunomodulatory effects of BTKi

	Cell type	Impact of BTKi on cell number
	Cell type	Ibrutinib	Acalabrutinib	Zanubrutinib
Innate immune system	Neutrophils	Decrease	–	–	Inhibit BTK	[25,26,27,28]
	Macrophages	Decrease	Decrease	–	Inhibit BTK by TLR, FcR and NLRP3-inflammasome	[29,30,31]
	Monocytes/DC	Decrease	Decrease	–	Inhibit BTK by TLR, FcR and NLRP3-inflammasome	[32,33,34, 37,38,39,40]
	TAM (nurse-like cells)	Decrease	–	–	Unknown	[35]
	MDSC	Decrease	–	Decrease	Inhibit BTK	[36,37,38,39]
	NK	Decrease	–	No change	Inhibit ITK	[41,42,43]
	NKT	Decrease	–	–	Unknown	[53,54,55]
	γδ T cells	Decrease	–	–	Unknown	[54, 55]
	Mast cells	Decrease	–	–	Inhibit BTK, ITK and TEC	[56, 57]
	Basophils/eosinophils	–	–	–	Prevent (Siglec)-8–induced cells death by inhibting BTK	[58]
Adaptive immune system	Tcells
	CD4⁺	Increase first then decrease	No change	Increase first then decrease	The receding tumor burden and ITK	[35, 37, 62, 63, 65,66,67,68]
	CD8⁺	Increase first then decrease	No change	Increase first then decrease	The receding tumor burden and ITK	[35, 37, 62, 63, 65,66,67,68]
	Th1	Increase	No change	No change	Mediated by RLK	[37, 65, 74, 75]
	Th2	Decrease	No change	No change	Inhibit ITK	[37, 65, 74, 75]
	Th17	Decrease	No change	No change	Inhibit ITK	[37, 65, 74, 75]
	Tregs	Decrease	–	Decrease	Inhibit ITK	[37, 65, 74, 75]
	B cells
	IgA production	Increase	Increase	–	Unknown	[90, 91]
	IgG production	Decrease	–	–	Unknown	[90]

ISSN: 2162-3619