Regarding the mechanism of action of pembrolizumab and lenvatinib combination therapy, a preclinical study including in vitro and in vivo studies showed that suppression of tumour-associated macrophages, regulatory T cells, and other constituents of the tumour-suppressive microenvironment resulted in decreases in TGF-β and IL-10, the downregulation of PD-1 and Tim3, and the upregulation of ICOS and OX40, thereby inducing tumour immunity through IL-12 [70]. Here, ICOS is linked to neoplasm.