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Fig. 3 | Cancer Cell International

Fig. 3

From: Modulation of the tumour microenvironment in hepatocellular carcinoma by tyrosine kinase inhibitors: from modulation to combination therapy targeting the microenvironment

Fig. 3

Immunomodulatory effect of sorafenib on HCC. Sorafenib was shown to activate NK cells by regulating the shedding of major histocompatibility complex class I-related chain A (MICA), interacting with macrophages, and inhibiting androgen receptor, but was also shown to inhibit NK cell proliferation through the pERK1/2 pathway. Its effect on altering macrophage polarization from M2 to M1 remains controversial. CD4+ and CD8+ T cell infiltration remained unchanged after sorafenib treatment. Moreover, sorafenib was shown to increase the numbers of TANs and the levels of CCL2 and CCL17, leading to a subsequent increase in Treg cell infiltration, but other studies reported that sorafenib inhibited the recruitment of Treg cells in HCC. TAM polarization and increased infiltration of TAMs and TANs were proposed to be induced by hypoxia after sorafenib treatment

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